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Medicinal plants used in the treatment of

tuberculosis - Ethnobotanical and
ethnopharmacological approaches
Article in Biotechnology advances · July 2017

DOI: 10.1016/j.biotechadv.2017.07.001
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Accepted Manuscript
Medicinal plants used in the treatment of tuberculosis -

Ethnobotanical and ethnopharmacological approaches
Javad Sharifi-Rad, Bahare Salehi, Zorica Z. Stojanović-Radić,

Patrick Valere Tsouh Fokou, Marzieh Sharifi-Rad, Gail B.
Mahady, Majid Sharifi-Rad, Mohammad-Reza Masjedi, Temitope
O. Lawal, Seyed Abdulmajid Ayatollahi, Javid Masjedi, Razieh
Sharifi-Rad, William N. Setzer, Mehdi Sharifi-Rad, Farzad
Kobarfard, Atta-ur Rahman, Muhammad Iqbal Choudhary, Athar
Ata, Marcello Iriti
PII: S0734-9750(17)30077-0
DOI: doi: 10.1016/j.biotechadv.2017.07.001
Reference: JBA 7134
To appear in: Biotechnology Advances
Received date: 29 December 2016
Revised date: 22 June 2017
Accepted date: 5 July 2017
Please cite this article as: Javad Sharifi-Rad, Bahare Salehi, Zorica Z. Stojanović-Radić,
Patrick Valere Tsouh Fokou, Marzieh Sharifi-Rad, Gail B. Mahady, Majid Sharifi-Rad,
Mohammad-Reza Masjedi, Temitope O. Lawal, Seyed Abdulmajid Ayatollahi, Javid
Masjedi, Razieh Sharifi-Rad, William N. Setzer, Mehdi Sharifi-Rad, Farzad Kobarfard,
Atta-ur Rahman, Muhammad Iqbal Choudhary, Athar Ata, Marcello Iriti , Medicinal
plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological
approaches, Biotechnology Advances (2017), doi: 10.1016/j.biotechadv.2017.07.001
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Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and

ethnopharmacological approaches
Javad Sharifi-Rada,*, Bahare Salehib*, Zorica Z. Stojanović-Radićc, Patrick Valere Tsouh

Fokoud,e, Marzieh Sharifi-Radf, Gail B. Mahadyg, Majid Sharifi-Radh, Mohammad-Reza
Masjedii, Temitope O. Lawalg,j, Seyed Abdulmajid Ayatollahia,k, Javid Masjedil, Razieh Sharifi-
Radm, William N. Setzern, Mehdi Sharifi-Rado,*, Farzad Kobarfarda,p , Atta-ur Rahmanq,
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Muhammad Iqbal Choudharyq, Athar Atar, Marcello Iritis,*
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CR
a
Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
b
Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases
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(NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Department of Biology and Ecology, Faculty of Science and Mathematics, University of Niš,
Višegradska 33, Niš, Serbia
AN
d
Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, College of Health
Sciences, University of Ghana, Accra LG 581, Ghana
M
e
Antimicrobial Agents Unit, LPMPS, Department of Biochemistry, Faculty of Science, University of
Yaoundé 1, Yaoundé 812, Cameroon
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f
Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran
g
Department of Pharmacy Practice, Clinical Pharmacognosy Laboratories, University of Illinois at
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Chicago, USA
h
Department of Range and Watershed Management, Faculty of Natural Resources, University of Zabol,
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Zabol, Iran
i
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung
Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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j
Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan, Nigeria
k
Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences
Tehran, Iran
l
Tobacco Control Strategic Research Center, Shahid Beheshti University of Medical Sciences Tehran,
Iran
m
Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran
n
Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA
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o
Department of Medical Parasitology, Zabol University of Medical Sciences, 61663335 Zabol, Iran
p
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Iran
q
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,
University of Karachi, Karachi 75270, Pakistan
r
Department of Chemistry, Richardson College for the Environmental Science Complex The University
of Winnipeg, Winnipeg, Canada
T
s
Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, Milan
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20133, Italy
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* Corresponding authors at: Phytochemistry Research Center, Shahid Beheshti University of Medical
Sciences, Tehran, Iran. E-mail address: javad.sharifirad@gmail.com (J. Javad Sharifi-Rad).
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Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases
(NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail address:
bahar.salehi007@gmail.com (B. Salehi).
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Department of Medical Parasitology, Zabol University of Medical Sciences, 61663335 Zabol, Iran. E-
mail address: mehdi_sharifirad@yahoo.com (M. Sharifi-Rad).
M
Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, Milan
20133, Italy. E-mail address: marcello.iriti@unimi.it (M. Iriti).
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ABSTRACT
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Tuberculosis is a highly infectious disease declared a global health emergency by the World Health
Organization, with approximately one third of the world’s population being latently infected with
Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation
phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to
prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with
second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and
fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to
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reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end,
many plant species, as well as marine organisms and fungi have been and continue to be used in various
traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited
source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in
adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their
adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and
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environmental adaptability of Mycobacterium. However, even if some natural products have still been
investigated in preclinical and clinical studies, the validation of their efficacy and safety as
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antituberculosis agents is far from being reached, and, therefore, according to an evidence-based
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approach, more high-level randomized clinical trials are urgently needed.
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Keywords:
Mycobacterium
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Multi drug-resistance
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Traditional healing systems
Herbal medicine
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Antimycobacterial agents
Evidence-based medicine
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1. Introduction
Pulmonary tuberculosis (TB) is a humankind disease. Available evidence shows that some pharaohs in
ancient Egypt suffered from TB and recent radiological studies using computerized tomography revealed
spinal involvement in some cases. Therefore, TB is a historical disorder that had centuries of history
accompanied with human life. Since the detection of tubercle bacilli as the causal agent by Robert Koch
in 1882, and after the introduction of first anti-TB drugs by Schatz and Waksman in 1940, great
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developments have transpired in the fields of biology, microbiology, pathogenesis, immunology, drug
therapy and, recently, molecular genetics of this disease and its etiological agent. However, TB is still a
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worldwide problem. It has been estimated, that almost one billion people have died from TB during the
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last 200 years (Paulson, 2013). According to the latest report, World Health Organization (WHO)
declared that, in 2014, nearly 1,400,000 people had died from TB, from this number, 890,000 were men,
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480,000 women and 140,000 were children. Currently, TB with HIV are the main killers globally. In the
year 2014, almost 9,600,000 people had TB, 5,400,000 of whom were men, 3,200,000 women and 1
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million children. Around 12% of these people were HIV positive. At the same time, 6,000,000 new cases
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of TB were reported by WHO, that is 63% of the total estimated figures. This means that almost 37% of
patients with TB were undiagnosed and/or unreported (WHO, 2015). In 2014, 480,000 cases of multi
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drug-resistant (MDR) TB were estimated, while only one quarter of this number, around 123,000 were
diagnosed and treated worldwide. According to the sustainable development goals (SDG), all countries
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are obliged to reduce the number of death from TB, 90% by the year 2030, and to reduce the number of
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new cases to 80%, simultaneously. In addition, all countries should plan in a manner that no family will
be compromised because of this disease. Following the Oslo meeting in 1995, WHO defined two major
targets as success criteria of national TB programs. First, at least 70% of patients should be diagnosed
(case finding), and at least 80% of smear positive cases should be cured (cure rate). After a vast struggle
and hard work at the national, regional and global level, and following the discovery of new rapid and
applicable molecular diagnostic techniques and affordable therapeutic regimens, WHO has modified its
strategy from ”Stop TB” to ”End TB“ strategy.
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MDR TB is defined as cases infected with tubercle bacilli that are resistant to the major essential drugs,
rifampin (RIF) and isoniazid (INH), while XDR (Masjedi et al., 2006; Masjedi et al., 2008; Velayati et
al., 2012; Masjedi et al., 2013) (extensively drug-resistant) refers to cases which are MDR and resistant to
fluoroquinolone and two injectable drugs (amikacin and capreomycin). Recently TDR (totally drug-
resistant) patterns were reported which include cases resistant to all antibiotics. These resistant cases raise
difficult issues in the subject of successful control and management of tuberculosis. Although 2-3 billion
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of currently living people are infected with tubercle bacilli, only 5-15% of them will develop active
disease during their lifetime, which is mainly pulmonary tuberculosis (Talavera et al., 2001; Tiemersma et
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al., 2011). This fact explains the complicated interaction between the microbe and the host, which is the
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subject of different branches of research (Smith, 2003).
Tuberculosis bacilli are mycobacteria related to the actinomycete group (the mycobacterium TB complex)
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which include human and bovine types, Mycobacterium africanum, M. microtti and M. canetti. These
aerobic bacilli in 80 to 90% of cases invade the lungs, and in 5 to 20% colonize other extra-pulmonary
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organs, mainly lymph nodes, bones and joints, and genitourinary system 9 (Tiemersma et al., 2011). The
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main route of entrance of tubercle bacilli into the body is in form of aerosol droplets via the lung. As
these microbes reach the alveoli, they face and are engulfed by alveolar macrophages, and may infect type
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II pneumocytes. Later, dendritic cells, T lymphocytes, cytokines and many other mediators and biologic
factors interfere and appear in the scene and lead to the development of typical granulomatas and necrosis
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which we are not described in detail in this introduction (Mehta et al., 1996; Tascon et al., 2000).
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The main strategy of TB treatment was focused on DOT‘s strategy, that is “Directly Observed Treatment
short course“, which is 6 months treatment. In the initial two months, the patient receives 4 major drugs
(RIF, INH, pyrazinamide, ethambutol) under close observation by health worker or defined volunteer
person, and the following 4 months will continue with two drugs (RIF and INH). This six months regimen
is recommended to all cases of pulmonary and extra-pulmonary cases including children and older
patients. As mentioned earlier, MDR TB which includes cases resistant to both RIF and INH, was
reported in 1990 by WHO and is a real obstacle in the general control of this disease worldwide. In the
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year 2006, XDR types were reported and it seems that 3.2% of all new cases of TB and 20% of those who
received treatment were MDR (Holtz and Cegielski, 2007; Chiang et al., 2010; Millardet al., 2015;
Ghanashyam, 2016). In the year 2014, almost 190,000 patients with MDR had died and only 50% of
those with MDR were treated successfully. With the introduction of linezolid (Farshidpour et al., 2013;
Lee et al., 2015) in 2000, and bedaquiline (Diacon et al., 2009; WHO, 2013) in 2009, WHO
recommended new therapeutic regimens to deal with MDR and XDR cases. A relevant issue in the field
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of tuberculosis is vaccine use. Historically, the extensively used vaccine worldwide is BCG (Bacillus
Calmette-Guérin) vaccine. This vaccine, made from a weak strain of Mycobacterium bovis, was
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introduced 80 years ago and is still recommended by WHO to be used in early childhood as one of the 6
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essential vaccines, particularly in prevalent areas. BCG vaccine is effective in preventing development of
severe forms of TB in children, mainly biliary tuberculosis and meningitis. This vaccine is less effective
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in preventing tuberculous disease among adults (Bedi, 2005).
Recent advances in the molecular biology and immunopathogenesis of mycobacterial diseases have led to
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extensive research in these fields and different vaccines have been introduced to be used as a preventive
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or therapeutic (Lalvani et al., 2013; Mangtani et al., 2014; Kaufmann et al., 2015). However, we should
wait for affordable and effective vaccines in the coming years. The complex scenario is the interaction
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between the immune system and tubercle bacilli after the preliminary infection, which, in most cases,
leads to latent tuberculosis infection (LTI). As mentioned earlier, in more than 80% of cases, the human
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body is able to contain the infection and the bacilli remain dormant through the whole life of infected
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people. This phenomenon is a subject of extensive research (Parrish et al., 1998; Wayne et al., 2001;
Cardona, and Ruiz-Manzano, 2004). It is worthwhile to mention that WHO, international organizations,
research institutions, charities and supporters altogether are working very hard to tackle different aspects
of this problem and to achieve the projected targets in the coming decades.
2. Traditional knowledge on plants used against tuberculosis
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Medicinal plants have been in use for centuries to cure various ailments including tuberculosis. Infusions,
macerations, tinctures and decoctions of medicinal plant parts such as leaves, roots, stem bark, stem,
flowers and fruits have been used for centuries as traditional treatments of TB by native people
worldwide. Commercial preparations of some of these remedies are available and continue to be used
with considerable success in affected communities. Even though ethnobotanical and
ethnopharmacological studies confirmed their wide use in the treatment of TB, the therapeutic and safe
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doses are still to be established for most of them. Most of the studies also failed to provide scientific
evidence to traditional beliefs and therapeutic practices. Therefore, this work is an attempt to document
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medicinal plants traditionally used to control TB. Different traditional healing systems have been applied
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to cure TB, ranging from the poor documented oral African medicine to the well documented Asian or
Chinese, Ayurveda and so on.

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2.1. Indigenous knowledge on tuberculosis
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The unique and exclusive indigenous knowledge in Africa is orally transferred to the next generation
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especially in rural communities (Lawal et al., 2014). Tuberculosis is believed to be a contagious disease
transmitted mainly through sharing contaminated food and eating-utensils, and droplet infection is known
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by the African traditional system by signs and symptoms that include cough, wheezing cough, labored
breathing and weight loss (Tabuti et al., 2010). However, some of these symptoms are not specific and
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can be related to other pulmonary diseases such as asthma, different infections, cancer and ordinary
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cough. In Ayurveda (Indian traditional medicine system), TB is aptly referred as Rajayakshma, a disease
of grave prognosis, along with ascites and marasmus, that spreads from one person to another (Jayana)
like the flight of birds. It is attributable to tissue emaciation or loss (Dhatukshaya) involved in
pathogenesis accompanied by metabolic dysfunction (Dhatwagninasana): fluid, blood, muscle, adipose
tissue and generative tissue are lost leading to immunosuppression (Debnath et al., 2012; Samal, 2016).
Conventional anti-TB medications have been prescribed to control symptoms, but they result in side
effects and, therefore, the use of herbal medicine has been promoted (Arya, 2011). Finally, traditional
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Chinese medicine cure TB by combining antibacterial treatments, strengthening QI (vital energy) and
administering herbs to protect the liver (Liu et al., 2008).
2.2. Medicinal plants used in African traditional medicine for the management of tuberculosis
A total of 222 plant species used in Africa for TB treatment were recorded, belonging to 71 families
(Table 1). The families with the most species of plants used to cure TB are Leguminosae (or Fabaceae, 28
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species) and Compositae (or Asteraceae, 20 species) (Table 1). Overall, the most frequently used plant
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parts are leaves, whole root and stem bark (Tabuti et al., 2010). The most frequently cited species are
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Erythrina abyssinica Lam. ex DC. and Allium sativum L. (4 occurrences), Ficus platyphylla Delile,
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Bidens pilosa L., Asparagus africanus Lam., Carissa edulis (Forssk.) Vahl. and Allium cepa L. (3
occurrences) (Table 1). The anti-TB activity of E. abyssinica and A. sativum have been demonstrated
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extensively. E. abyssinica crude methanol extract showed antimicrobial activity on the sensitive strain
H37Rv and the rifampicin resistant strain TMC-331, with MIC values of 0.39 mg/ml and 2.35 mg/ml,
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respectively (Bunalema, 2010). A. sativum extract inhibited both non-MDR and MDR M. tuberculosis
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isolates, with MIC values ranging from 1000 to 3000 μg/mL (Hannan et al., 2011). The leaf ethanol
extract of B. pilosa exhibited activity against M. tuberculosis at 100 μg/mL (Gautam et al. 2007). C.
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edulis showed antibacterial activity against slow (M. tuberculosis, M. kansasii) and fast (M. fortuitum and
M. smegmatis) growing mycobacteria (Mariita, 2006). A. cepa anti-mycobacterial activities have

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previously been reported (Arya, 2011).

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Table 1. Common medicinal plants in African traditional medicine for tuberculosis treatment.
Plant family Botanical name Mode of preparation/administration Locations References
Acanthaceae Acanthus pubescens (Thomson ex Roots are used to treat TB and related Uganda (Tabuti et al.,
Oliv.) Engl. diseases 2010)
Brillantaisia owariensis P. Beauv. Leaves are used to treat TB and related Uganda (Tabuti et al.,
diseases 2010)
Hygrophila auriculata (Schumach.) Leaves and whole plant are used to treat Uganda,
T (Tabuti et al.,
Heine TB and related diseases I Ghana
P 2010; Nguta etl
al., 2015)
Acanthus montanus (Nees) T.Anderson Leaf infusion is used in the treatment of
R Nigeria (Ogbole and
TB C Ajaiyeoba, 2010)
Aizoaceae Carpobrotus edulis (L.) N.E.Br. Leaf decoction is used orally for the
S South Africa (Lawal et al.,
treatment of TB 2014)
Amaranthaceae Chenopodium ambrosioides L. Leaves are used in curing TB and related
U South Africa, (Nguta etl al.,
symptoms N Ghana 2015; Lall aand
A Meyer, 1999)
Achyranthes aspera L. Flowers are used to treat TB and related Uganda (Tabuti et al.,
diseases
M 2010)
Amaranthus spinosus L. Leaves are used to treat TB and related Uganda (Tabuti et al.,
D diseases 2010)
Amaryllidace Allium cepa L. E Leaves and bulbs are used in the Ghana, (Ogbole and
T treatment of TB Nigeria, Ajaiyeoba, 2010;
South Africa Lawal et al.,
2014; Nguta etl
E P al., 2015)
Allium sativum L.C Bulbs, tubers and leaves are used for the South Africa, (Faleyimu et al.,
treatment of TB and related symptoms Nigeria, 2009; Greene et
C Ghana al., 2010; Tabuti
A et al., 2010;
Nguta etl al.,
2015)
Brunsvigia grandiflora Lindl. Bulbs against coughs and colds South Africa (Madikizela,
2014)
Haemanthus albiflos Jacq. Used for the treatment of TB South Africa (Lawal et al.,
2014)
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Tulbaghia acutiloba Harv. Used for the treatment of TB South Africa (Lawal et al.,
2014) [
Tulbaghia violacea Harv. Used for the treatment of TB South Africa (Lawal et al.,
2014)
Anacardiaceae Mangifera indica L. Stem bark is used to treat TB and related Uganda (Tabuti et al.,
diseases 2010; Orodho et
al., 2014)
Pistacia aethiopica Kokwaro Leaves are used to treat TB Kenya
T (Mariita, 2006)
Rhus rogersii Schönland Used in the treatment of TB-related South Africa
P (Greene et al.,
diseases or their symptoms 2010)
Sclerocarya birrea (A Rich) Hochst. Bark is used in the treatment of TB- R I South Africa (Greene et al.,
related diseases or their symptoms
C 2010)
Spondias mombin L. Leaf infusion is used in the treatment of Nigeria (Ogbole and
TB Ajaiyeoba, 2010)
S
Annonaceae Annona senegalensis Pers. Leaves or roots are pound, boiled and
U Nigeria (Ofukwu et al.,
filtered for drinking
N 2008)
Apiaceae Centella asiatica (L.) Urb. Dried pound bark is boiled in water for
A Nigeria (Ofukwu et al.,
drinking 2008)
Centella coriacea Nannf. Used for the treatment of TB
M South Africa (Lawal et al.,
2014)
Daucus carota L. Used for the treatment of TB
D South Africa (Lawal et al.,
E 2014)
Apocynaceae Alstonia boonei De Wild T Leaf decoction and bark maceration are Nigeria (Ogbole and
P used in the treatment of TB Ajaiyeoba, 2010)
C E
Araujia sericifera Brot. Used for the treatment of TB South Africa (Lawal et al.,
2014)
Carissa edulis (Forssk.) Vahl.
C Leaves, roots and root bark are used in South Africa, (Mariita, 2006;
A the treatment of TB-related diseases or Uganda, Tabuti et al.,
their symptoms Kenya 2010; Greene et
al., 2010)
Cryptolepis sanguinolenta (Lindl.) Root bark is used for the treatment of Uganda (Bunalema,
Schltr. TB symptoms and lung infections 2010; Orodho et
al., 2014)
Arecaceae Cocos nucifera L. Husk decoction is used in the treatment Nigeria, (Ogbole and
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of TB Ghana Ajaiyeoba, 2010;

Nguta etl al.,
2015)
Elaeis guineensis Jacq. Oil soup is used in the treatment of TB Nigeria (Ogbole and
Ajaiyeoba, 2010)
Asclepiadaceae Asclepias fruticosa L. Roots are used in the treatment of TB- South Africa (Greene et al.,
related diseases or their symptoms 2010)
Gomphocarpus physocarpus E. Mey. Leaves are used to treat TB and related Uganda
T (Tabuti et al.,
symptoms I P 2010)
Asparagaceae Asparagus africanus Lam. Shoots and stem (wood) are used for the South Africa, (Tabuti et al.,
treatment of TB R Uganda 2010; Lawal et
C al., 2014;
S Madikizela,
2014)
Asparagus falcatus (L.) Oberm. Leaves and roots are used to treat TB
U South Africa (Madikizela,
N 2014)
Balanophoraceae Thonningia sanguinea Vahl. Fruit decoction is used in the treatment
A Nigeria (Ogbole and
of TB Ajaiyeoba, 2010)
Bignoniaceae Stereospermum kunthianum Cham. Boiled leaves or bark or roots in water to
M Nigeria (Ofukwu et al.,
drink for TB or their symptoms 2008)
Burseraceae Boswellia dalzielii Hutch. D Bark is pounded, powdered and mixed Nigeria (Ofukwu et al.,
E with porridge for the treatment of TB or 2008)
T their symptoms
Commiphora africana (A.Rich.) Endl.
P Bark boiled in water for the treatment of Nigeria (Ofukwu et al.,
TB or their symptoms 2008)
Canellaceae Warburgia salutaris (G. Bertol.) Chiov.
E Leaves and stem bark are used for the South Africa, (Tabuti et al.,
C treatment of TB or symptoms Uganda 2010; Greene et
C al., 2010; Greene
et al., 2010)
Warburgia ugandensis Sprague
A Used for the treatment of TB or their Uganda, (Orodho et al.,
symptoms Kenya, 2014)
Tanzania
Cannabaceae Cannabis sativa L. Used for the treatment of TB South Africa (Lawal et al.,
2014)
Capparaceae Capparis erythrocarpos Isert. Roots are used for the treatment of TB Uganda (Tabuti et al.,
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or symptoms 2010)
Capparis tomentosa Lam. Used for the treatment of TB or Uganda (Tabuti et al.,
symptoms 2010)
Maerua edulis (Gilg & Gilg-Ben.) Tubers are used for the treatment of TB Uganda (Tabuti et al.,
DeWolf. or symptoms 2010)
Caprifoliaceae Scabiosa albanensis R.A. Dyer Used for the treatment of TB South Africa (Lawal et al.,
2014)
Caricaceae Carica papaya L. Leaves and seeds are used in the South Africa,
T (Tabuti et al.,
treatment of TB-related diseases or their Uganda
P 2010; Greene et
symptoms al., 2010)
Caryophyllaceae Silene undulata Aiton Used for the treatment of TB R I South Africa (Lawal et al.,
C 2014)
Celastraceae Cassine papillosa (Hochst.) Kuntze Used to cure TB-related symptoms South Africa (Lall aand
Meyer, 1999)
Maytenus senegalensis (Lam.) Excell U S
Roots and root bark are used to cure TB- South Africa (Tabuti et al.,
related symptoms
N 2010)
Clusiaceae Garcinia kola Heckel; Garcinia spp. Leaf decoction is used in the treatment Nigeria, (Ogbole and
of TB Uganda, Ajaiyeoba, 2010;
A
M Kenya Orodho et al.,
2014)
Colchicaceae D Leaf decoction is used in the treatment Nigeria (Ogbole and
Gloriosa superba L.
E of TB Ajaiyeoba, 2010)
Combretaceae Anogeissus leiocarpus (DC.) Guill. &
T Roots boiled in water for drinking in the Nigeria (Faleyimu et al.,
Perr. P treatment of TB 2009; Ofukwu et
al., 2008)
Anogeissus schimperi Hochst. ex Hutch.
E Bark socked or boiled in water to drink Nigeria (Ofukwu et al.,
& Dalziel C for the treatment of TB 2008)
Combretum apiculatum Sond.

C Dried leaves boiled for drinking in the Nigeria (Ofukwu et al.,
A treatment of TB 2008)
Combretum erythrophyllum (Burch) Leaves used in the treatment of TB- South Africa (Greene et al.,
Sond. related diseases or their symptoms 2010)
Combretum molle R. Br. Ex G. Don. Used in the treatment of TB-related South Africa (Lall aand
symptoms Meyer, 1999)
Terminalia brownii Fresen. Bark boiled in salted water for drinking Nigeria (Ofukwu et al.,
in the treatment of TB 2008)
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Terminalia phanerophlebia Engl. & Roots are used for the treatment of TB South Africa (Madikizela,
Diels 2014)
Terminalia sericea Burch ex D.C. Bark are used in the treatment of TB- South Africa (Greene et al.,
Asteraceae Artemisia afra Jacq. ex Willd. Used for the treatment of TB South Africa (Lawal et al.,
2014)
Aspilia africana (Pers.) C. D. Adams Roots are used for the treatment of TB Uganda (Tabuti et al.,
and related symptoms T 2010)
Bidens pilosa L. Flowers or whole plant are used to treat Uganda,
P (Tabuti et al.,
TB I Ghana, 2010; Lawal et
R South Africa al., 2014)
Conyza ivifolia Burm.f. Used in the treatment of TB-related
C South Africa (Meyer et al.,
symptoms such as cough, fever, blood in 2002)
the sputum S
Conyza sumatrensis (Retz.) E. Walker Leaves are used in the treatment of TB
U Uganda (Tabuti et al.,
(syn. C. floribunda) or related symptoms
N 2010)
Gutenbergia cordifolia Benth. ex Oliv. Roots and leaves are used for the Uganda (Tabuti et al.,
treatment of TB and related symptoms 2010)
Helichrysum appendiculatum (L.f.)
A
Used in the treatment of TB-related South Africa (Meyer et al.,
Less.
M
D the sputum
Helichrysum caespititium (DC.) Sond.E Exudates are used against TB and South Africa (Meyer et al.,
ex Harv. related disorders, such as broncho- 2002)
pneumonial diseases, and symptoms
P T such as cough, fever, blood in the
E sputum
Helichrysum imbricatum (L.) Less.
C The tea and infusion are used as a South Africa (Meyer et al.,
demulcent in coughs and in pulmonary 2002)
C affections
Helichrysum krausii Sch.Bip.
A The smoke of dried flowers and seeds in South Africa (Meyer et al.,
a pipe is used for the relief of cough and 2002)
as a remedy for TB
Helichrysum leiopodium DC. Used in the treatment of TB-related South Africa (Meyer et al.,
the sputum
13
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Helichrysum melanacme DC. Used in the treatment of TB-related South Africa (Lall aand
Helichrysum nudifolium (L.) Less. Tea and infusion are used as a South Africa (Meyer et al.,
demulcent in coughs and in pulmonary 2002)
affections
Helichrysum odoratissimum (L.) Sweet Leaves are used in the treatment of TB- Uganda, (Tabuti et al.,
related symptoms South Africa 2010)
Microglossa pyrifolia (Lam.) Kuntze Roots are used in the treatment of TB- Uganda
T (Tabuti et al.,
related symptoms P 2010)
Nidorella anomala Steetz. Used in the treatment of TB-related
symptoms R I South Africa (Lall aand
Meyer, 1999)
Nidorella auriculata DC. Used in the treatment of TB-related
C South Africa (Lall aand
Senecio serratuloides DC. var.
serratuloides symptoms U S
Used in the treatment of TB-related South Africa (Lall aand
Meyer, 1999)
Vernonia amygdalina Delile Pounded fresh leaves fresh and squeezed
N Nigeria, (Mariita, 2006;
for drinking are used in the treatment of Uganda, Ofukwu et al.,
TB-related symptoms. Kenya 2008; Tabuti et
A
Root barks used to treat TB and asthma al., 2010)
Vernonia woodii O.Hoffm.
M
Used in the treatment of TB-related South Africa (Meyer et al.,
Dsymptoms such as cough, fever, blood in 2002)
E the sputum
Convolvulaceae Ipomoea batatas (L.) Lam. T Peeling maceration is used in the Nigeria (Ogbole and
treatment of TB Ajaiyeoba, 2010)
Ipomoea involucrata P.Beauv.
P Leaf infusion is used to cure TB Nigeria (Ogbole and
E Ajaiyeoba, 2010)
Costaceae Costus afer Ker Gawl.
C Stem decoction and leaf infusion are Nigeria (Ogbole and
C used in the treatment of TB Ajaiyeoba, 2010)
A
Crassulaceae Kalanchoe spp. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
related symptoms 2010)
Bryophyllum pinnatum (Lam.) Oken Leaf infusion is used in the treatment of Nigeria (Ogbole and
TB Ajaiyeoba, 2010)
14
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Cucurbitaceae Momordica foetida Schum. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Lagenaria sphaerica (Sond.) Naudin Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Momordica charantia L. Whole plant is used to treat asthma, TB, Kenya (Mariita, 2006)
and pneumonia
Cyperaceae Cyperus articulatus L. Roots are used to treat TB Ghana (Nguta etl al.,
T 2015)
Cyperus latifolius Poir. Roots are used in the treatment of TB- Uganda
P (Tabuti et al.,
Cyperus rotundus L. ssp. rotundus Roots are used in the treatment of TB-
R I Uganda (Tabuti et al.,
related symptoms C 2010)
Ebanaceae Diospyros mespiliformis Hochst Leaves/bark are used in the treatment of South Africa (Greene et al.,
TB-related diseases or their symptoms 2010)
U S
Euclea natalensis A. DC. Used in the treatment of TB-related
N South Africa (Lall aand
symptoms A Meyer, 1999)
Euclea divinorum Hiern. Roots are used in the treatment of TB- Uganda (Tabuti et al.,
related symptoms
M 2010)
Euphorbiaceae Bridelia micrantha (Hochst.) Baill. Bark is used in the treatment of TB- South Africa (Greene et al.,
D 2010)
Croton macrostachyus Hochst. ex E Stem bark is used to treat TB, asthma, Kenya (Mariita, 2006)
Ferret et Galinier T and coughs
Croton megalocarpus Hutch. P Leaves are used to treat TB Kenya (Mariita, 2006)
E
Croton pseudopulchellus Pax
C Used to treat TB-related symptoms South Africa (Lall aand
C Meyer, 1999)
Euphorbia scarlatica (L) O. Kuntz
A Stems are used to treat common cold Kenya (Mariita, 2006)
and TB
Euphorbia schimperiana Scheele Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Euphorbia tirucalli L. Stems are used to treat TB and asthma Kenya (Mariita, 2006)
Tragia brevipes Pax Roots are used in the treatment of TB- Uganda (Tabuti et al.,
15
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Tragia subsessilis Pax Roots are used in the treatment of TB- Uganda (Tabuti et al.,
Geraniaceae Pelargonium sidoides DC. Roots are used to treat coughs and TB South Africa (Mativandlela et
al., 2006)
Pelargonium reniforme Curtis Roots are used in the treatment of South Africa (Mativandlela et
coughs and tuberculosis al., 2006)
Gunneraceae Gunnera perpensa L. Used in the treatment of TB-related
symptoms P T
South Africa (Lall aand
Meyer, 1999)
Hypoxidaceae Hypoxis argentea Harv. ex Baker Used for the treatment of TB
I South Africa (Lawal et al.,
R 2014)
Hypericaceae Hypericum revolutum Vahl Used for the treatment of TB or
C Uganda (Tabuti et al.,
symptoms S 2010)
Iridaceae Zygotritonia bongensis (Pax) Mildbr Bulb tincture is used to cure TB Nigeria (Ogbole and
U Ajaiyeoba, 2010)
Lamiaceae Achyrospermum carvalhoi Gürke Leaves are used in the treatment of TB-
N Uganda (Tabuti et al.,
related symptoms
A 2010)
Clerodendrum capitatum (Willd.) Leaf decoction is used in the treatment Nigeria (Ogbole and
Schum. & Thonn of TB
M Ajaiyeoba, 2010)
Hoslundia opposita Vahl Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Iboza multiflora (Benth.) E. A. Bruce
E D Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
T related symptoms 2010)
Iboza riparia (Hochst.) N. E. Br.
P Leaves and stem (wood) are used in the Uganda (Tabuti et al.,
treatment of TB-related symptoms 2010)
E
Leonotis intermedia Lindl. Leaves and stems are used in the South Africa (Madikizela,
C treatment of colds, coughs, bronchitis, 2014)
C asthma and TB
Leonotis nepetifolia (L.) R. Br.
A Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Mentha longifolia (L.) L. Used for the treatment of TB South Africa (Lawal et al.,
2014)
Ocimum gratissimum L. Bulb is boiled in water for drinking and Nigeria (Ofukwu et al.,
used in the treatment of TB-related 2008; Ogbole
symptoms. and Ajaiyeoba,
16
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Leaf tincture is used in the treatment of 2010)

TB
Ocimum suave Willd. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Plectranthus barbatus Andr. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Pycnostachys erici-rosenii R.E.Fr. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
related symptoms T 2010)
Rosmarinus officinalis L. Used for the treatment of TB South Africa
P (Lawal et al.,
2014)
Lauraceae Cryptocarya latifolia Sond. Used to cure TB-related symptoms R I South Africa (Lall aand
C Meyer, 1999)
Persea americana Mill. Leaves, stem (wood) and seeds are used Uganda (Tabuti et al.,
in the treatment of TB-related symptoms 2010)
U S
Leguminosae Abrus precatorius L. Leaves and roots are used to treat TB,
N South Africa, (Ogbole and
(Fabaceae) bronchitis, whooping cough, chest
A Nigeria Ajaiyeoba, 2010;
complaints and asthma. Madikizela,
Seed decoction is used in TB treatment
M 2014)
Acacia albida Delile Used in the treatment of TB-related Nigeria (Faleyimu et al.,
symptoms
D 2009)
Acacia hebecladoides Harms E Used in the treatment of TB-related Nigeria (Faleyimu et al.,
T symptoms 2009)
Acacia hockii De Wild. Stem bark, stem (wood) and fruits are Uganda (Tabuti et al.,
P used in the treatment of TB-related 2010; Orodho et
E symptoms al., 2014)
Acacia karroo Hayne
C Used for the treatment of TB South Africa (Lawal et al.,
2014)
Acacia mearnsii De Wild.
C Stem bark is used in the treatment of Uganda (Tabuti et al.,
A TB-related symptoms 2010)
Acacia nilotica (L.) Delile Used in the treatment of TB-related Nigeria (Faleyimu et al.,
symptoms 2009)
Acacia polyacantha Willd. Stem bark is used in the treatment of Uganda (Tabuti et al.,
TB-related symptoms 2010)
17
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Acacia xanthophloea Benth. Used in the treatment of TB-related South Africa (Lall aand
Albizia coriaria Oliv. Used in the treatment of TB-related Uganda (Orodho et al.,
symptoms 2014)
Baphia nitida Lodd. Bark infusion is used to cure TB Nigeria (Ogbole and
Ajaiyeoba, 2010)
Cassia alata L. Fairly dried leaves boiled for drinking in Nigeria (Ofukwu et al.,
the treatment of TB-related symptoms 2008)
T
Cassia occidentalis L. Dried leaves boiled for drinking in the I Nigeria
P (Ofukwu et al.,
treatment of TB-related symptoms 2008)
Cassia petersiana Bolle Bark is used in the treatment of TB-
C R South Africa (Greene et al.,
2010)
Desmodium repandum (Vahl) DC. Leaves are used for the treatment of TB
S Uganda (Tabuti et al.,
symptoms and pulmonary infections 2010)
Entada abbysinica A.Rich. N U
Used in the treatment of TB-related Kenya, (Orodho et al.,
symptoms A Tanzania 2014)
Erythrina abyssinica Lam. ex DC. Root and stem barks are used for the
M Uganda, (Mariita, 2006;
treatment of TB symptoms and Kenya, Tabuti et al.,
D pulmonary infections Tanzania 2010; Bunalema,
E 2010; Orodho et
T al., 2014)
Indigofera arrecta Benth. ex Harv. & Roots are used in the treatment of TB- South Africa (Madikizela,
Sond. related symptoms 2014)
E P
Lonchocarpus cyanescens (Schumach. Leaf infusion is used in the treatment of Nigeria (Ogbole and
& Thonn.) Benth. C TB Ajaiyeoba, 2010)
Mucuna pruriens (L.) DC.
C Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Ormocarpum trichocarpum
A Roots are used in the treatment of TB- Uganda (Tabuti et al.,
(Taub.)Harms related symptoms 2010)
Peltophorum africanum Sond Bark is used in the treatment of TB- South Africa (Greene et al.,
Piliostigma reticulatum (DC.) Hochst. Used in the treatment of TB-related Nigeria (Faleyimu et al.,
symptoms 2009)
18
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Piliostigma thonningii (Schumach.) Stem (wood) is used in the treatment of Uganda (Tabuti et al.,
Milne-Redh. TB-related symptoms 2010)
Schotia brachypetala Sond Bark used in the treatment of TB-related South Africa (Greene et al.,
diseases or their symptoms 2010)
Senna siamea (Lam.) Irwin & Barneby Stem bark is used in the treatment of Uganda (Tabuti et al.,
TB-related symptoms 2010)
Tamarindus indica L. Leaves are used in the treatment of TB- Uganda, (Faleyimu et al.,
related symptoms Nigeria
T 2009; Tabuti et
P al., 2010)
Loranthaceae Tapinanthus dodoneifolius (DC.) Leaves, Bark boiled in water for Nigeria (Ofukwu et al.,
Danser drinking in the treatment of TB R I 2008)
Malvaceae Adansonia digitata L.

C
Dried leaves boiled in water for drinking
2 times for 24 days only in the treatment
S Nigeria (Ofukwu et al.,
2008; Faleyimu
of TB U et al., 2009)
Ceiba pentandra (L.) Gaertn. Fresh leaves is boils in water for Nigeria (Ofukwu et al.,
drinking and are used in the treatment of 2008)
TB A N
Grewia villosa Willd. Roots are used in the treatment of TB-
M South Africa (Greene et al.,
Cola acuminata (P.Beauv.) Schott & Fruit infusion is used in the treatment of
D Nigeria (Ogbole and
Endl. TB Ajaiyeoba, 2010)
Glyphaea brevis (Spreng.) Monach.
E Leaf decoction is used in TB treatment Nigeria (Ogbole and
Ajaiyeoba, 2010)
T
Hibiscus sabdariffa L. P Leaf is used in the treatment of TB Nigeria (Ogbole and
E Ajaiyeoba, 2010)
Melastomataceae Antherotoma senegambiensis (Guill. &
C Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
Perr.) Jacq.-Fél. related symptoms 2010)
A C
Dissotis rotundifolia (Sm.) Triana Leaves are used in the treatment of TB Ghana (Nguta etl al.,
2015)
Meliaceae Azadirachta indica A. Juss. Seeds, leaves, stem (wood) and stem Ghana, (Tabuti et al.,
bark are used in the treatment of TB Uganda 2010; Nguta etl
al., 2015)
Ekebergia capensis Sparm. Used in the treatment of TB-related South Africa (Lall aand
19
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Menispermaceae Jateorhiza macrantha (Hook.f.) Exell & Leaf infusion is used in the treatment of Nigeria (Ogbole and
Mendonça TB Ajaiyeoba, 2010)
Moraceae Ficus asperifolia Miq. Leaf maceration is used in TB treatment Nigeria (Hannan et al.,
2011)
Ficus platyphylla Delile Stem bark, squeezed fresh leaves or Nigeria, (Ofukwu et al.,
boiled for drinking in the treatment of Uganda, 2008; Tabuti et
TB-related symptoms South Africa al., 2010; Lawal
T et al., 2014)
Ficus sur Forssk Bark and roots are used to treat TB andI South Africa
P (Lawal et al.,
lung ulceration 2014)
R (Madikizela,
C 2014)
Moringaceae Moringa oleifera Lam. Seeds are used in the treatment of TB-
S Uganda, (Faleyimu et al.,
related symptoms Nigeria 2009; Tabuti et
U al., 2010)
Musaceae Musa nana Lour. Leaf meal is used in the treatment of TB
N Nigeria (Ogbole and
A Ajaiyeoba, 2010)
Myristicaceae Pycnanthus angolensis (Welw.) Warb. Bark maceration is used in TB treatment Nigeria (Ogbole and
M Ajaiyeoba, 2010)
Myrsinaceae Maesa lanceolata Forssk. Roots are used in the treatment of TB- Uganda (Tabuti et al.,
related symptoms
D 2010)
Myrtaceae Callistemon citrinus (Curtis) Skeels Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
T E related symptoms 2010)
Corymbia citriodora (Hook.) K.D.Hill
P Used for the treatment of TB South Africa (Lawal et al.,
& L.A.S.Johnson E 2014)
Eucalyptus spp. Leaves and stem bark are used in the Uganda, (Tabuti et al.,
C treatment of TB-related symptoms Kenya, 2010; Orodho et
C Tanzania al., 2014)
Psidium guajava L.
A Bark maceration is used in the treatment Nigeria (Ogbole and
of TB Ajaiyeoba, 2010)
Syzygium cordatum Hochst. ex Krauss Used for the treatment of TB South Africa (Lawal et al.,
2014)
Olacaceae Ximenia caffra Sond. var. caffra Leaves are used in the treatment of TB- South Africa (Greene et al.,
20
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Orobanchaceae Alectra sessiliflora (Vahl) Kuntz Leaf infusion is used in TB treatment Nigeria (Ogbole and
Ajaiyeoba, 2010)
Phyllanthaceae Phyllanthus fraternus G.L. Webster Leaves are used in the treatment of TB Ghana (Nguta etl al.,
2015)
Piperaceae Piper capense L.f. Roots used in the treatment of TB- South Africa (Greene et al.,
Poaceae Coix lacryma-jobi L. Glumes are used in the treatment of TB Ghana (Nguta etl al.,
T 2015)
Cymbopogon giganteus Chiov. Leaves are used in the treatment of TB Ghana
P (Nguta etl al.,
Cymbopogon citratus (DC.) Stapf. Leaf infusion is used in TB treatment

R I Nigeria
2015)
(Ogbole and
C Ajaiyeoba, 2010)
Polygalaceae Polygala fruticosa P.J.Bergius Whole plant is used in TB treatment
S South Africa (Madikizela,
2014)
Polygala myrtifolia L. Used in the treatment of TB-related
U South Africa (Lall aand
symptoms N Meyer, 1999)
Securidaca longipedunculata Fresen. Roots are used in the treatment of TB-
A South Africa, (Tabuti et al.,
related diseases or their symptoms Uganda 2010; Greene et
M al., 2010)
Polygonaceae Rumex crispus L. Used in the treatment of TB-related South Africa (Lall aand
symptoms
D Meyer, 1999)
Primulaceae Rapanea melanophloeos (L.) Mez. E Used in the treatment of TB-related South Africa (Lall aand
T symptoms Meyer, 1999)
Rhamnaceae Berchemia discolor (Klotzsch) Hemsl. Bark/leaves are used in the treatment of South Africa (Greene et al.,
TB-related diseases or their symptoms 2010)
P
Rhamnus prinoides L’Herit.
E Leaves and stem (wood) are used in the Uganda (Tabuti et al.,
C treatment of TB-related diseases or their 2010)
symptoms
C
Ziziphus mucronata Willd. Bark, leaves and roots are used in the South Africa (Greene et al.,
A treatment of TB-related diseases or their 2010; Lawal et
symptoms al., 2014)
Rosaceae Prunus africana (Hook.f.) Kalkman Used for the treatment of TB South Africa (Lawal et al.,
2014)
Rubiaceae Coffea spp. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
21
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Gardenia ternifolia Schumach. & Roots are used in the treatment of TB- Uganda (Tabuti et al.,
Thonn. ssp. jovis-tonantis (Welw.) related diseases or their symptoms 2010)
Hiern.
Pentanisia prunelloides Schinz Roots are used to treat TB and chest South Africa (Madikizela,
disorders 2014)
Rubia cordifolia L. Used in the treatment of TB-related Uganda, (Orodho et al.,
diseases or their symptoms Kenya 2014)
Rubia petiolaris DC. Used for the treatment of TB South Africa
T (Lawal et al.,
P 2014)
Rutaceae Agathosma betulina (P.J.Bergius)
Pillans
Used for the treatment of TB
R I South Africa (Lawal et al.,
2014)
Citrus aurantifolia (Christm.) Swingle Fruit infusion is used in TB treatment
C Nigeria (Ogbole and
S Ajaiyeoba, 2010)
Citrus medica L. Fruit infusion is used in TB treatment Nigeria (Ogbole and
U Ajaiyeoba, 2010)
Clausena anisata (Willd.) Hook.f. ex Used for the treatment of TB
N South Africa (Lawal et al.,
Benth. A 2014)
Harrisonia abyssinica Oliv. Root bark is used in the treatment of Uganda (Tabuti et al.,
TB-related diseases or their symptoms
M 2010)
Ptaeroxylon obliquum (Thunb.) Radlk. Used for the treatment of TB South Africa (Lawal et al.,
D 2014)
Teclea nobilis Del. E Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
T related diseases or their symptoms 2010)
Toddalia asiatica (L.) Lam.
P Roots are used to treat TB Kenya (Mariita, 2006)
Zanthoxylum chalybeum Engl. Roots are used in the treatment of TB- Uganda, (Madikizela,
related diseases or their symptoms Kenya 2014; Orodho et
C E al., 2014)
Zanthoxylum gillettii De Wild. Waterm.
C Stem bark is used to treat TB and Kenya (Mariita, 2006)
asthma
Sapindaceae Dodonaea angustifolia L. f. Leaves are used in the treatment of TB- Uganda (Tabuti et al.,
A related diseases or their symptoms 2010)
Haplocoelum foliolosum (Heirn) Stem bark is used in the treatment of Uganda (Tabuti et al.,
Bullock TB-related diseases or their symptoms 2010)
Hippobromus pauciflorus Radlk. Used for the treatment of TB South Africa (Lawal et al.,
2014)
22
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Sapotaceae Vitellaria paradoxa C.F.Gaertn Oil decoction is used in TB treatment Nigeria (Ogbole and
Ajaiyeoba, 2010)
Solanaceae Capsicum frutescens L. Used for the treatment of TB South Africa (Lawal et al.,
2014)
Solanum incanum L. Fruits are used in the treatment of TB Kenya (Bunalema,
symptoms and chest-related infections 2010; Orodho et
al., 2014)
Solanum torvum Sw. Unripe fruits/leaves are used to treat TB Ghana (Nguta etl al.,
P T 2015)
Withania somnifera (L.) Dunal Used for the treatment of TB
I South Africa (Lawal et al.,
R 2014)
Verbenaceae Clerodendrum myricoides Roots are used to treat TB and chest
C Kenya (Mariita, 2006)
(Hochst)Vatke disorders S
Lantana trifolia L. Leaves are used for the treatment of TB Uganda (Tabuti et al.,
and related symptoms 2010)
U
Lantana camara L. Leaves are used to treat TB, pneumonia,
N Kenya (Mariita, 2006)
and chest pains
A
Lantana trifolia L. Leaves are used to treat TB and cough Kenya (Mariita, 2006)
Vitaceae Cyphostemma cyphopetalum (Fresen.) Stem (wood), leaves and tubers are used Uganda (Tabuti et al.,
Desc. Ex Wild & Drumm.
M
in the treatment of TB-related diseases 2010)
D
or their symptoms
Rhoicissus tridentata (L.f.) Wild & Tubers, leaves and stem (wood) are used South Africa, (Tabuti et al.,
R.B.Drumm. T E in the treatment of TB-related diseases Uganda 2010; Greene et
P or their symptoms al., 2010)
Xanthorrhoeaceae Aloe vera var. barbadensis
E Leaves are used in the treatment of TB Ghana (Nguta etl al.,
2015)
Zingiberaceae
C C
Zingiber officinale Roscoe Rhizomes are used in TB treatment Ghana,
Uganda
(Tabuti et al.,
2010; Nguta etl
A al., 2015)
Aframomum melegueta (Roscoe) Fruit tincture is used in TB treatment Nigeria (Ogbole and
K.Schum. Ajaiyeoba, 2010)
Zygophyllaceae Balanites aegyptiaca (L.) Delile Stem bark and roots are used in the Uganda (Tabuti et al.,
treatment of TB-related diseases or their 2010)
symptoms
23
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2.3. Medicinal plants used in Asian traditional medicine for the management of tuberculosis
From Asian traditional medicine including Ayurveda, 84 plant species have been recorded, belonging to 44 plant families. The most represented
families are Leguminosae (or Fabaceae, 8 species), Lamiaceae (6 species) and Compositae (4 species) (Table 2). The most cited species are
Adhatoda vasica (5 occurences), Tinospora cordifolia (3 occurences), Allium sativum, Acalypha indica, Asparagus racemosus, Cedrus deodara,
T
P
Pinus contorta, Piper longum, Rubus occidentalis, Aloe vera, Glycyrrhiza glabra, Vitex negundo and Vitex trifolia (2 occurences) (Table 2).
I
R
Adhatoda vasica oil from leaves, roots and flowers significantly inhibited the growth of M. tuberculosis B19-4 at a concentration of 4 µg/mL
C
(Gautam et al., 2012). As well, the anti-TB activity of Tinospora cordifolia, Allium sativum, Acalypha indica, Aloe vera, Vitex negundo and Vitex
S
trifolia have been documented (Arya, 2011).
N U
A
M
Table 2. Common medicinal plants used in Asia for tuberculosis treatment.
D
Plant family Botanical name T E Mode of preparation/administration Locations References
P Ayurveda (Ayyanar
E and
C Ignacimuthu,
Leaves, flowers and roots are used for the treatment of 2008; Arya,
2011;
C asthma, gasping cough, bronchitis, cold and TB.
Acanthaceae Adhatoda vasica Nees
A Debnath et
Leaf juice (30 ml) with honey removes mucus from
al., 2012;
lungs
Gautam et
al., 2012;
Alvin et al.,
2014;
24
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Tewari et
al., 2015)
Andrographis paniculata Ground leaves with mortar and pestle, served with honey Indonesia
(Burm.f.) Nees for TB treatment
Amaranthaceae Spinacia oleracea L. Leaf decoction is taken orally against weight loss and Iraq (Ahmed,
TB 2016)
Amaryllidaceae Bulbs are used for the treatment of asthma, cough, Ayurveda (Arya, 2011)
Allium cepa L. T
bronchitis and TB
I P Iraq, (Arya, 2011;
Bulbs are used for the treatment of asthma, cough,
R Ayurveda Viswanathan
Allium sativum L. bronchitis and TB Decoction of bulbs is used orally to et al., 2014;
treat TB C Ahmed,
S 2016)
Apiaceae Centella asiatica (L.) Urb. Ayurveda, (Ayyanar
Whole plant is used for leprosy, bronchitis, asthma and
U Indonesia and
TB. N Ignacimuthu,
Boiled water extract of ground plant (all aerial parts) is
A 2008; Alvin
used for TB treatment
M et al., 2014)
Ayurveda (Samal,
Hemidesmus indicus R.Br Root is used in Rasayana as adjuvant therapy for TB
D 2016)
Apocynaceae
Tabernaemontana coronaria (L.) Malaysia (Mohamad
Leaves are used to treat TB
Willd. T E et al., 2011)
P Old cane jaggery is used in Bhringarajasava, a liquid Ayurveda (Samal,
formulation (30 mL) administered in an equal quantity 2016)
Borassus flabellifer L. of water, 30 min after meal, thrice a day during the
E
Arecaceae C intensive phase of TB treatment and followed up to 6-8
C months
Licuala spinosa Thunb. Malaysia (Mohamad
A Leaves are used to treat TB
et al., 2011)
Hydroalcoholic extract is used as part of 200 mg Liv- Ayurveda (Samal,
Berberidaceae Berberis aristata DC. 600 capsule administer thrice a day as adjuvant therapy 2016)
for TB (hepatoprotective properties)
Boraginaceae Heliotropium indicum L. Leaves, flowers or roots decoctions to treat TB Arabian (Saganuwan,
Peninsula 2010)
25
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Brassicaceae Nasturtium indicum (L.) DC. Boiled water extract of all aerial parts is used for TB Indonesia (Alvin et al.,
treatment 2014)
Commiphora mukul (Hook. ex Used for centuries. Commercial products are promoted Ayurveda (Dhanabal et
Burseraceae
Stocks) Engl. for use in TB al., 2015)
Used in Bhringarajasava, a liquid formulation (30 mL) Ayurveda (Samal,
administered in an equal quantity of water, 30 min after 2016)
Calophyllaceae Mesua ferrea L.
meal, thrice a day during the intensive phase of TB
T
treatment and followed up to 6-8 months
Roots are used to treat TB Ayurveda (Chandra
Pseudostellaria heterophylla
I P and Rawat,
(Miq.) Pax R 2015)
Caryophyllaceae
Stellaria rubra Scop. C Ayurveda (Chandra
Whole plant juice rich in vitamin C is used in treatment
S and Rawat,
of weakness after illness, lung congestion and TB
U 2015)
Used in Bhringarajasava, a liquid formulation (30 mL)
N Ayurveda (Samal,
Combretaceae Terminalia chebula Retz
A
M
Commelinaceae Rhoeo spathacea (Sw.) Stearn Indonesia (Alvin et al.,
Boiled water leaf extract is used for TB treatment
D 2014)
Used in Bhringarajasava, a liquid formulation (30 mL)
E Ayurveda (Samal,
Eclipta prostrata L. T
P meal, thrice a day during the intensive phase of TB
Pluchea indica (L.) Less. Boiled water leaf and root extracts are used for TB Indonesia (Alvin et al.,
Compositae
E
(Asteraceae) C treatment 2014)
Saussurea lappa (Decne.)
C Roots are used in Rasayana capsules as ½ part in Ayurveda (Samal,
Sch.Bip.
A adjuvant therapy for TB 2016)
Taraxacum officinale F.H. Wigg Leaf decoction is taken orally against TB Iraq (Ahmed,
2016)
Kalanchoe integra (Medik.) Ayurveda (Arya, 2011)
Leaves are used in the treatment of TB
Kuntze
Crassulaceae
Benincasa hispida (Thunb.) Cogn. Philippine (Batugal et
Remedy against TB
al., 2004)
26
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Trichosanthes dioica Roxb. Roots and fruits are used in the treatment of TB Ayurveda (Arya, 2011)
Ayurveda (Arya, 2011;
Leaves are used as expectorant, diuretic, respiratory
Acalypha indica L. Dhanabal et
disease, pneumonia, asthma and TB
al., 2015)
Ayurveda (Poonam
Stem bark decoction (30-50 ml) is taken orally thrice a
Jatropha curcas L. and Singh,
Euphorbiaceae day for TB treatment
T 2009)
Mallotus philippensis (Lam.) Glandular trichomes and hairs of fruit are used in the Ayurveda (Arya, 2011)
Müll.Arg. treatment of TB I P
Ricinus communis L. Indonesia (Alvin et al.,
Boiled water extract of leaves and roots are used for TB
R 2014)
Hydnocarpus anthelminthica Chinese (Wang et al.,
Flacourtiaceae
Pierre ex Laness S C
Seeds are used against leprosy and TB
2010)
Ayurveda (Namita and
Canscora decussata (Roxb.)
Gentianaceae
Schult. & Schult.f. N U
Roots are used in the treatment of TB Mukesh,
2012)
Leaves, fruits and roots are used in the treatment of TB Ayurveda (Namita and
A
Colebrookea oppositifolia Sm. M Mukesh,
2012)
Leaves, flowers and seeds are used in the treatment of
D Ayurveda (Namita and
Ocimum sanctum L. TB
E Mukesh,
T 2012)
P Ayurveda (Namita and
Lamiaceae Leaves and seeds as well as a decoction of the stem bark Mukesh,
Vitex negundo L. E is used to treat TB 2012; Ahuja
C et al., 2015)
Vitex trifolia L.
C Ayurveda, (Batugal et
Indonesia al., 2004;
A Leaves, roots and fruits are used in the treatment of TB.
Arya, 2011;
Boiled water extract of leaves is used for TB treatment
Alvin et al.,
2014)
Lauraceae Cinnamomum cassia (Nees & Iraq (Ahmed,
Powder of stem bark is used against cough and TB
T.Nees) J.Pres 2016)
27
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Cinnamomum tamala (Buch.- administered in an equal quantity of water, 30 min after 2016)
Ham.) T.Nees & Eberm. meal, thrice a day during the intensive phase of TB
Cinnamomum zeylanicum Blume
T
Leaves are used to treat cough, respiratory tractP Ayurveda (Gautam et
Acacia senegal (L.) Willd. I
infections, bronchitis R al., 2012)
Caesalpinia pulcherrima (L.) Sw. Leaves and flowers are used in the treatment of TB Ayurveda (Arya, 2011)
Caesalpinia sappan L.
C
Boiled water extract of chopped pieces is used for TB
S Indonesia (Alvin et al.,
2014)
Flemingia strobilifera (L.) W.T. Leaves are used to treat respiratory diseases including
U Malaysia (Mohamad
Leguminosae Aiton symptoms of TB N et al., 2011)
(Fabaceae) Chinese, (Namita and
Roots to treat TB.
A Ayurveda Mukesh,
Glycyrrhiza glabra L. Roots are used in Rasayana capsules as 1 parts in
M 2012; Samal,
adjuvant therapy for TB
2016)
Mimosa pudica L. E D
Leaves and roots are used in the treatment of TB Ayurveda (Arya, 2011)
Trigonella foenum-graecum L.T Oil, leaves, roots and seeds are used as cough Arabian (Saganuwan,
P suppressant, to treat asthma, pneumonias and TB Peninsula 2010)
Ayurveda (Nair, 1998;
Liliaceae
E
Asparagus racemosus Willd. Roots are useful in TB, cough and bronchitis Warrier,
C 2002)
Malvaceae Hibiscus tilliaceus L. Indonesia (Alvin et al.,
Boiled water extract of leaves is used for TB treatment
A C 2014)
Ayurveda (Dhanabal et
Stem and leaves benefit the general weakness and TB.
Tinospora cordifolia (Willd.) al., 2015;
Used in Rasayana capsules as 1 parts in adjuvant therapy
Menispermaceae Miers Samal,
of TB
2016)
Tinospora crispa (L.) Miers ex Leaves are used to treat TB Malaysia (Mohamad
28
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Hook. f. & Thoms. et al., 2011)
Ayurveda (Poonam
Leaf paste is used against TB, 1 tea spoon twice a day by
Meliaceae Azadirachta indica Juss. A. and Singh,
oral route.
2009)
Myristicaceae Myristica fragrans Houtt.
meal, thrice a day during the intensive phase of TBT
treatment and followed up to 6-8 months P
Myrtus communis L. Fruits are used in the treatment of TB
R I Ayurveda (Arya, 2011)

Myrtaceae Syzygium aromaticum (L.) Merr.
C
& L.M.Perry meal, thrice a day during the intensive phase of TB
S
U
Ophioglossaceae Helmintostachys zeylanica (L.) Philippines (Batugal et
Used to treat TB N
Hook. A al., 2004)
Pericarp is used in Rasayana capsules as 1 parts in Ayurveda (Samal,
Emblica officinalis Gaertn.
M 2016)
Phyllanthus fraternus G.L. Freshly prepared decoction of aerial parts is used as part Ayurveda (Samal,
Phyllanthaceae Webster of 10 mg and administered thrice a day as adjuvant
D 2016)
Etherapy of TB
T Ayurveda (Tewari et
Emblica officinalis Gaertn. Fruit juice is useful for cough, asthma and TB
P al., 2015)
E Ayurveda ( Nair, 1998;
Cedrus deodara Roxb. Leaves are used in the treatment of TB Warrier,
2002)
C
C Ayurveda (Nair, 1998;
Pinaceae Pinus contorta Douglas. ex
The inner bark to treat TB Warrier,
Loudon.
A 2002)
Pinus pinea L. Leaves, roots and stem are used to treat TB Arabian (Saganuwan,
Pennisula 2010)
Fruit is used in Rasayana capsules as ½ parts in adjuvant Ayurveda (Arya, 2011;
Piperaceae Piper longum L.; Piper spp.
therapy of TB Samal,
29
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Used in Bhringarajasava, a liquid formulation (30 mL) 2016)

administered in an equal quantity of water, 30 min after
Plantago major L. Fruits and leaves are used to treat TB, hemorrhage and Arabian (Saganuwan,
Plantaginaceae
pneumonia Peninsula 2010)
Poaceae Imperata cylindrical (L.) Philippine (Batugal et
Rhizome decoction is used to treat TB T
Raeuschel al., 2004)
Saccharum spontaneum L. Philippine (Batugal et
To treat TB
I P al., 2004)
Sorghum bicolor (L.) Moench
R
Seeds, flowers and leaves are used to treat cough and TB Arabian (Saganuwan,
C Peninsula 2010)
Polygonaceae Rumex hastatus D. Don Root and bark are used in the treatment of TB
S Ayurveda (Arya, 2011)
Ranunculus ternatus Thunb.

U
Roots are used alone or combined with other herbal Chinese (Zhang et
remedies in the treatment of TB.
N al., 2015)
Ranunculaceae
Radix Ranunculi Ternati is now the only commercially
A
available medicine for the treatment of TB
Rosaceae Prunus amygdalus Batsch
M
Leaves, oil and flowers are used to treat TB and cough Arabian (Saganuwan,
D Pennisula 2010)
Prunus armeniaca L. E Kernels are used in the treatment of TB Ayurveda (Arya, 2011)
T Ayurveda (Nair, 1998;
Rubus occidentalis L. P A decoction of the roots is used in the treatment of TB Warrier,
E 2002)
Ixora chinensis Lam. Philippine (Batugal et
Remedy against incipient TB, hemorrhage and headache
al., 2004)
C
C Ayurveda (Arya, 2011;
Rubiaceae
Morinda citrifolia L.
A Leaves, roots and fruits are used in the treatment of TB Tewari et
al., 2015)
Morinda citrifolia L. Boiled water extract of aerial parts are used for TB Indonesia (Alvin et al.,
treatment 2014)
Salicaceae Flacourtia ramontchi L'Hér. Leaves, roots, bark and fruits are used in TB treatment Ayurveda (Arya, 2011)
30
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Simaroubaceae Brucea javanica (L.) Merr. Indonesia (Alvin et al.,

Ground fruits with mortar and pestle for TB treatment
2014)
Hydroalcoholic extract is used as part of 200 mg Ayurveda (Samal,
Solanum nigrum L. capsules Liv-600 administered thrice a day as adjuvant 2016)
Solanaceae therapy of TB
Root is used in Rasayana capsules as 1 parts in adjunct Ayurveda (Samal,
Withania somnifera L.
treatment of TB T 2016)
Verbenaceae Lantana camara L. Boiled water extract of leaves and flowers are used for Indonesia (Alvin et al.,
TB treatment 2014)
I P
Rhizome is used in Rasayana capsules as ¼ part in Ayurveda (Samal,
Alpinia galanga (L.) Willd. R
adjuvant therapy of TB 2016)
Rhizome is used in Rasayana capsules as ½ part in Ayurveda (Samal,
Curcuma longa L.
adjuvant therapy of TB S C 2016)
Zingiberaceae Used in Bhringarajasava, a liquid formulation (30 mL)
U Ayurveda (Samal,
Elettaria cardamomum (L.) administered in an equal quantity of water, 30 min after
N 2016)
Maton meal, thrice a day during the intensive phase of TB
A
Kaempferia galanga L. Whole plant is used as remedy for common cold,
M Philippine (Batugal et
bronchitis and TB al., 2004)
E D
T
2.4. Medicinal plants used in South Pacific and American traditional medicine for the management of tuberculosis
E P
From American traditional medicine, which, in some cases, is a mixture of African and Asian knowledges, we recorded 52 plant species,
C
belonging to 27 families, used to treat TB and related symptoms (Table 3). The most represented families are Compositae (12 species),
C
A
Leguminosae (or Fabaceae, 5 species) and Lamiaceae (4 species) (Table 3). Most cited species is Chenopodium ambrosiodes L., whose anti-TB
activity has been reported previously (Ahmad et al., 2016).
31
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Table 3. Medicinal plants used against tuberculosis in Americas.
Plant family Botanical name Mode of preparation/administration Locations References
Amaranthaceae Chenopodium ambrosiodes L. 1 bunch of fresh leaves in 500 ml water as Brazil, (Storey and
juice/syrup/condensed milk/tea, daily dosage Amazonia Salem,1997;
200/400 ml, for the treatment of lung Leitão et al.,
problems, cough and TB T 2013)
Apocynaceae Aspidosperma carapanauba Pichon. Used in the treatment of TB-related symptoms
P Amazonia (Storey and
I Salem,1997)
Parahancornia amapa (Huber) Ducke Used in the treatment of TB-related symptoms
R Amazonia (Storey and
Salem,1997)
Aspidosperma carapanauba Pichon Used in the treatment of TB-related symptoms
C Amazonia (Storey and
S Salem,1997)
Asphodelaceae Aloe arborescens Mill. Syrup and juice are indicated for the treatment
U Brazil (Leitão et
of lung problems, cough and TB al., 2013)
A N
Leaves and gel from leaves are used in the Ayurveda (Arya, 2011;
treatment of TB. Samal,
Aloe vera (L.) Burm.f. Hydroalcoholic extract as parts of 200 mg
M 2016)
capsule Liv-600 administered thrice a day as
D
Barringtoniaceae Barringtonia asiatica (L.) Kurz E Stem bark is used in treating TB South (WHO,1998)
T Pacific
Bignoniaceae Arrabidaea chica (H.B.K.) Verlot.
P Used in the treatment of TB-related symptoms Amazonia (Storey and
E Salem,1997)
Brassicaceae Nasturtium officinale R. Br Syrup and juice are indicated for the treatment Brazil (Leitão et
C of lung problems, cough and TB al., 2013)
Combretaceae
A C
Terminalia catappa L. Leaves are used to treat bronchitis and TB Tahiti (WHO,1998)
Compositae Artemisia spp. Tea is indicated for the treatment of lung Brazil (Leitão et
problems, cough and TB al., 2013)
Bidens pilosa L. Tea is indicated for the treatment of lung Brazil (Leitão et
32
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Elephantopus mollis Kunth. Tea is indicated for the treatment of lung Brazil (Leitão et
Heterocondylus alatus (Vell.) R.M.King Tea and syrup are indicated for the treatment Brazil (Leitão et
and H.Rob. of lung problems, cough and TB al., 2013)
Hypochaeris brasiliensis (Less.) Hook. Tea and juice are indicated for the treatment of Brazil (Leitão et
and Arn. lung problems, cough and TB T al., 2013)
Mikania laevigata Sch. Bip. ex Baker Tea, juice and syrup are indicated for the
I P Brazil (Leitão et
treatment of lung problems, cough and TB al., 2013)
Solidago chilensis Meyen C R
Juice is indicated for the treatment of lung Brazil (Leitão et
Vernonia phaeoneura Toledo U S
Juice is indicated for the treatment of lung Brazil (Leitão et
Vernonia polyanthes Less. A N
Tea, juice and syrup are indicated for the Brazil (Leitão et
Vernonia westiniana Less.
M
Syrup is indicated for the treatment of lung Brazil (Leitão et
D problems, cough and TB al., 2013)
Vernonia spp.
E Tea and syrup are indicated for the treatment Brazil (Leitão et
T of lung problems, cough and TB al., 2013)
P
Spilanthes acmella (L.) L.
E A handful of fresh leaves and flowers in 500 Amazonia (Storey and
ml water as juice/condensed milk, daily dosage Salem,1997)
C ad libitum
Crassulaceae Tea, juice and syrup are indicated for the Amazonia (Storey and
Kalanchoe brasiliensis Cambess.
C treatment of lung problems, cough and TB Brazil Salem,1997;
A Leitão et al.,
2013)
Euphorbiaceae Euphorbia fidjiana Boiss. Leaf is used in treating TB South (WHO,1998)
Pacific
Goodeniaceae Scaevola taccada (Gaertner) Roxb. Leaves, stem bark and roots are used to treat South (WHO,1998)
coughs and TB Pacific
33
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Lamiaceae Mentha pulegium L. Tea, juice and syrup are indicated for the Brazil (Leitão et
Mentha x piperita L. Tea is indicated for the treatment of lung Brazil (Leitão et
Ocimum campechianum Mill. Used in the treatment of TB-related symptoms Brazil (Leitão et
T al., 2013)
Ocimum gratissimum L. Tea, juice and syrup are indicated for the
I P Brazil (Leitão et
Leguminosae Hymenaea spp. C R
Tea and syrup are indicated for the treatment Brazil (Leitão et
(Fabaceae) of lung problems, cough and TB al., 2013)
Acacia cochliacantha Humb. & Bonpl. U S
Shoots are used to treat TB and cold Mexico (Coronado-
ex Willd. Aceves et
N al., 2016)
Bowdichia virgilioides Η.Β.Κ. Used in the treatment of TB-related symptoms
A Amazonia (Storey and
Salem,1997)
Hymenaea courbaril L. Used in the treatment of TB-related symptoms Amazonia (Storey and
M Salem,1997)
Caesalpinia ferrea Mart.
D 2 dry pods in 1 liter water as infusion/tea, daily Amazonia (Storey and
E dosage ad libitum Salem,1997)
Loranthaceae Struthanthus concinnus Mart.
T Syrup are indicated for the treatment of lung Brazil (Leitão et
P problems, cough and TB al., 2013)
Struthanthus marginatus (Desr.) G. Don
E Tea, juice and syrup are indicated for the Brazil (Leitão et
C treatment of lung problems, cough and TB al., 2013)
Lythraceae Punica granatum L.

C Treatment of TB, pulmonary diseases or Amazonia (Storey and
A symptoms of these disorders Salem,1997)
Malvaceae Hibiscus tiliaceus L. var. tiliaceus Stem bark is used to prepare a remedy against South (WHO,1998)
cough which is also used for TB. Pacific
Leaves are used in treating cough, sore throat
and open wounds
In the Solomon Islands, parts of the plant are
used in treating cuts, TB and conjunctivitis.
34
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In New Guinea, the bark is used to make a

cough remedy which is also used for TB
Malva spp. Syrup is indicated for the treatment of lung Brazil (Leitão et
Meliaceae Carapa guianensis Aubl. Used in the treatment of TB-related symptoms Amazonia (Storey and
Salem,1997)
Myrtaceae Eucalyptus camaldulensis Dehnh. Leaves are used to treat TB, bronchitis and
T Mexico (Coronado-
cough P Aceves et
I al., 2016)
Syzygium malaccense (L.) Merr. & Perry Leaves are used to treat bronchitis and TB.
R South (WHO,1998)
Stem bark infusion is used to treat TB and Pacific
digestive tract problems.
C
Eugenia uniflora L. Tea is indicated for the treatment of lung
S Brazil (Leitão et
problems, cough and TB
U al., 2013)
Orbiaceae Bischofia javanica Blume The cambium of the plant is used to treat TB
N South (WHO,1998)
A Pacific
Piperaceae Potomorphe peltata ( L ) Miq. Used in the treatment of TB-related symptoms Amazonia (Storey and
M Salem,1997)
Poaceae Cymbopogon citratus (DC.) Stapf Tea, juice and syrup are indicated for the Brazil (Leitão et
D treatment of lung problems, cough and TB al., 2013)
Rhamnaceae Ampelozizyphus amazonicus Ducke.
T E Used in the treatment of TB-related symptoms Amazonia (Storey and
Salem,1997)
Rubiaceae Morinda citrifolia L. P Liquid pressed from young fruit is used in the South (WHO,1998)
E treatment of TB. Pacific
Rutaceae Used for the treatment of TB, pulmonary South (WHO,1998)
Citrus limon (L.) Osbeck
C disease or symptoms of these diseases Pacific
Citrus aurantium L.
C Indicated for the treatment of lung problems, Brazil (Leitão et
A cough and TB al., 2013)
Solanaceae Capsicum frutescens L. Used as a remedy for TB South (WHO,1998)
Pacific
Urticaceae Dendrocnide harveyi (Seemann) Chew A preparation made from scrapings of the South (WHO,1998)
stem bark is used in treating illnesses Pacific
described as pain in the lungs with vomiting
35
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of blood (TB)
Zingiberaceae Used in the treatment of TB-related symptoms Amazonia (Storey and

Zingiber officinale Roscoe.
Salem,1997)
To summarize, most of plant species belongs to Leguminosae (Fabaceae) and Compositae families. Amongst all the identified species, only few
T
are shared across continents. Allium cepa, Allium sativum, Aloe vera, Azadirachta indica, Lantana camara, Centella asiatica and Withania
P
I
somnifera were recorded in Asia and Africa (Fig. 1). On the other hand, Bidens pilosa, Capsicum frutescens, Chenopodium ambrosiodes, Hibiscus
R
tiliaceus, Cymbopogon citratus and Zingiber officinale were recorded in South Pacific-Americas and Africa, while only Morinda citrifolia was
C
S
identified both in Asia and South Pacific-Americas (Fig. 1). In general, very little uniformity has been observed in the plants mentioned,
U
highlighting the low consensus regarding TB remedies among the different traditional healing systems. This is likely due to the poor
N
A
experimentation or evidence of efficacy for TB treatment, as well as the limited availability and accessibility of some endangered medicinal
species.
M
E D
P T
C E
A C
36
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Africa
South Pacific-
222 6 Americas T
0
52 I P
7 1 C R
Asia U S
84 N
A
M
Fig. 1. Distribution of medicinal plants identified in the traditional treatment of tuberculosis across continents.
E D
P T
C E
A C
37
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3. Targeting multidrug resistance in tuberculosis: management with phytochemicals and

medicinal plants
3.1. Impact of MDR- and XDR-TB on public health
Despite significant advances in treating the disease, tuberculosis continues to be a serious global
health threat, with over 10.4 million cases, and 1.8 million deaths reported in 2015 (Smith et al., 2004;
T
WHO, 2015; Nguyen, 2016; WHO, 2016). Mycobacterium tuberculosis (MTb), the etiologic agent of
IP
tuberculosis, is now considered one of the most successful pathogens among those causing infectious
CR
diseases, and the incidence of MTb infections is on the rise globally due, in part, to the advent of
US
HIV/AIDS. The continued prevalence of MTb is due to the fact that this pathogen has an innate ability to
survive host defense mechanisms, as well as the lack of new therapies, the inappropriate use of anti-TB
AN
drugs, disease states that complicate treatment such as diabetes mellitus and HIV, as well as the
emergence of multi-drug resistant (MDR-TB) and extensively drug resistant (XDR-TB) strains (WHO,
M
2015).
ED
Over the last two decades, there has been a focus on the research and development of novel
therapies for TB and several drugs have been evaluated in clinical trials (WHO, 2016). However, the
PT
number of effective drugs for TB is still very small, and treatment is complicated and very lengthy,
leading to patient non-compliance and an increase in drug resistance. Over the past 40 years, the
CE
resistance of MTb has moved from mono-drug to multidrug resistance (MDR), extensively drug resistant
AC
(XDR), and eventually totally drug resistant (TDR), through sequential accumulation of resistance
mutations as reported by Nguyen et al., (2016). MDR-TB strains are resistant to both isoniazid and
rifampicin, and these strains were responsible for over 480,000 reported cases and approximately 210,000
deaths in 2013(Nguyen, 2016). Extensively drug-resistant (XDR) MTb strains are also resistant to the
quinolones and other second-line drugs and have been reported in at least 100 countries (WHO, 2015).
The morbidity of XDR is 40-50% and poses a serious public health threat, especially in areas with high
HIV prevalence. Antibiotic resistance of MTb strains continues to be a serious global health threat as
38
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some clinical strains have developed the means to evade all available antibiotics (Adhvaryu and Vakharia,
2011; Mishra et al., 2015; WHO, 2016).
As a consequence, there is an urgent need to develop novel anti-tuberculosis agents, particularly
adjunct treatments that may be used to reverse antibiotic resistance, treat MDR- and XDR-TB, and to
enhance the immune system to improve MTb recovery rates. In addition, most of the anti-TB drugs
currently target metabolic reactions and proteins that are critical for the proliferation of M. tuberculosis
T
IP
(Adhvaryu and Vakharia, 2011). Future studies should focus on research and development of new drugs
based on novel molecular targets related to the establishment of mycobacterial dormancy in human
CR
macrophages or inhibition of bacterial virulence factors that interfere with the signaling pathways of host
US
cells and affect immunity, leading to the persistence of the disease (Koul et al., 2011).
AN
3.2. Natural products for MDR- and XDR-TB
Medicinal plants have been used since the beginning of time to treat all diseases, including
M
infectious diseases, and have been excellent leads for the development of new drugs. In fact, over the past
ED
25 years, almost 50% of new drugs reviewed and approved by the US Food and Drug Administration
have been derivatives of natural products (Newman and Cragg, 2007; Kinghorn et al., 2011; Cragg and
PT
Newman, 2013; Atanasov et al., 2015). Reviews of recently published scientific literature show that there
are more than 350 species of plants used for the treatment of TB, from countries around the world, and
CE
many naturally occurring compounds have been isolated and identified with activity against MTb, MDR-
AC
TB and XDR-TB (Camacho‐Corona et al., 2008; Samad et al., 2008). The following is an overview of
some of the classes of natural products showing some promising activity against MDR- and XDR-TB.
3.3. Bisbenzylisoquinolone alkaloids
In a study by Sureram et al. (2012) bisbenzylisoquinoline alkaloids including tiliacorinine, 20-
nortiliacorinine and tiliacorine isolated from roots of the edible plant Tiliacora triandra, as well as one
synthetic derivative, 130-bromotiliacorinine, were active against MDR-TB strains. The 59 strains of M.
39
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tuberculosis included 12 isolates resistant to isoniazid (INH) and rifampin (RMP); five isolates resistant
to INH, RMP, and ethambutol (EMB); 23 isolates resistant to INH, RMP, and streptomycin (SM); nine
isolates resistant to INH, RMP, EMB, and SM; one isolate resistant to INH, RMP, EMB, and ofloxacin
(OFX); one isolate resistant to INH, RMP, SM, and OFX; and eight isolates resistant to INH, RMP, EMB,
SM, and OFX. The results of this study showed that tiliacorinine, 20-nortiliacorinine, tiliacorine, and 130-
bromotiliacorinine were active against MDR-MTB strains with median inhibitory concentration (MIC)s
T
IP
ranging from 0.7 to 6.2 µg/mL. Cytotoxicity in normal MRC-5 (human fetal lung fibroblast) cell line was
also determined. The alkaloids were cytotoxic in this cell line with median inhibitory concentration (IC50)
CR
of 3.13-20.0 µg/mL (Sureram et al., 2012).
3.4. Cinnamic acid derivatives

US
AN
In a 2011 study by Lakshmanan et al., (2012) a compound isolated from the rhizomes of
M
Kaempferia galanga and identified as ethyl p-methoxycinnamate (EPMC) was tested against MTb strains.
Antimycobacterial activity of EPMC was evaluated in MTb strains H37Ra (ATCC 25177) and H37Rv
ED
(ATCC 25618). Eight MTb clinical isolates, six of which from patients with MDR-TB, were obtained
from the Swedish National Strain Collection at the Swedish Institute for Infectious Disease Control
PT
(SMI), Solna, Sweden. The results of this study showed that EPMC inhibited the growth of all MTb
CE
strains tested, with a MIC of 0.485 mM. Four strains, irrespective of their drug resistance profiles (fully
susceptible or MDR), were inhibited at 0.242 mM. EPMC toxicity was also tested on the human
AC
macrophage cell line THP-1 cells. An IC50 value of 3.8 mM was reported, indicating that EPMC was not
toxic to macrophage cells at concentrations that could inhibit M. tuberculosis (Lakshmananet al., 2011).
Interestingly, the study also showed that the MDR strains did not exhibit higher MIC value than the
susceptible ones, suggesting that the mechanism of action may be different from the target of any of the
current anti-TB drugs (Lakshmananet al., 2011).
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3.5. Fungal metabolites
Ganihigama et al. (2015) evaluated the anti-MTb activity of 27 naturally occurring compounds
from fungi against MDR-TB isolates. Many of these natural products included anthraquinones,
diterpenoids, alkaloids and flavonoids. The fungal metabolites were tested against a non-virulent H37Ra
strain of M. tuberculosis and showed MIC values ranging from 3.1 µg/mL to > 100µg/mL. Among the
compounds tested, vermelhotin exhibited activity with MIC of 3.1 mg/mL (Ganihigama et al., 2015).
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Vermelhotin, a tetramic acid isolated from an unidentified marine fungus (CRI247-01) demonstrated
antimycobacterial activity towards five reference strains (MIC 3.1 - 6.2 µg/mL) and exhibited activity
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against the MDR-TB strains with MIC ranging between 1.5 µg/mL and 12.5 µg/mL (Ganihigama et al.,
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2015). Unfortunately, this compound was also cytotoxic in normal cells, MRC-5 cell line (human lung
fibroblast cells), with IC50 value of 6.97 µg/mL.

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3.6. Iridoids
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Plants used in the Ayurvedic system of medicine containing iridoids, terpenes and other
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compounds have been shown to exert anti-MTb activities (Kumar et al., 2013). In one study on tree bark
from Plumeria bicolor, a plant from India commonly known as Champa, several iridoids have been
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isolated and identified (Kumar et al., 2013). A methanol extract of the dried bark of P. bicolor, plumericin
and isoplumericin were tested against susceptible MTb and four MDR-TB strains (Kumar et al.,
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2013).The extract showed a MIC between 20-25 µg/mL for all strains tested. Plumericin was very active
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against all strains with a MIC between 1.3 and 2.1 µg/mL, with higher activity against the MDR strains.
Isoplumericin was also active with MICs between 2.0-2.6 µg/mL for all strains tested. No cytotoxicity
was reported for other cell lines.
3.7 Marine natural products
New interesting marine natural products have also been discovered with relevant activity against
MTb and MDR-TB. From marine Streptomyces spp., cyclomarin A, a novel anti-inflammatory cyclic
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peptide, was isolated and showed high activity against MTb with MIC of 0.3 µg/mL (Lee and Suh, 2016).
The MIC90 of the drug was 2.5 μM after 5 days of treatment, suggesting a high efficacy within short
treatment times. The occurrence of anti-mycobacterial metabolites from marine invertebrates, namely
sponges, corals and gorgonians has been recently investigated (Daletos et al., 2016; Sansinenea and Ortiz,
2016). The compound (–)-8,15-diisocyano-11(20)-amphilectene, a diterpene isolated from the Carribean
sponge Svenzea flava, showed a promising activity with MIC value of 3.2 µg/mL; the calculated
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selectivity index (SI; i.e., IC50/MIC) of compound was equal to 10.2, suggesting that amphilectane-type
diterpenes are important anti-tuberculosis pharmacophores (Nieves et al., 2016). Agelasines, purine
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diterpenes isolated from Agelasidae (Agelas spp.) marine sponges, were found to exhibit biological
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activity against the dormant state of MTb, which plays an important role in latent tuberculosis infection
(Arai et al., 2014). Very recently, three haliclocyclamines, dimeric 3-alkyl piridinium alkaloids isolated
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from the Indonesian marine sponge Haliclona spp., showed a dose-dependent anti-mycobacterial activity,
with the highest inhibition zone (10 mm) at 5 µg/disc (Maarisit et al., 2017).
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3.8. Peptides
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Anti-mycobacterial peptides have been recently reviewed (Silva et al., 2016; Dong et al., 2017),
though they have been investigating since many decades. In the 1960’s, a cyclic peptide named
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griselimycin (GM) was discovered from Streptomyces spp.; it was effective against MTb, though its
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pharmacokinetic properties were poor (Holzgrabe, 2015). In 2015, Rolf Müller and colleagues retested
GM after they increased the metabolic stability of the peptide by alkylating a proline residue in position 8.
A novel metabolically stable cyclohexyl derivative was obtained with improved penetration of the
mycobacterial cell wall, with a MIC of 0.06 μg/mL. The activity against MDR-TB was similar.
Investigation on the mechanism of action showed that there was an amplification of the dnaN gene. This
gene encodes for DnaN, a DNA polymerase sliding clamp that anchors the DNA to DNA polymerase,
thus enhancing the replicatory strength of the enzyme and accelerating DNA replication and repair in
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prokaryotes. DnaN is a molecular target of GM, and GM derivatives appear to bind to a hydrophobic
pocket of the DNA polymerase sliding clamp, making it an extremely novel mechanism of action (Lee
and Suh, 2016).
Lassomycin, a peptide composed of 16 amino acids, was identified from Lentzea kentuckyensis
IO0009804, another actinomycete. This peptide had activity against MDR and XDR MTb, with MICs
ranging from 0.41 to 1.65 μM (Lee and Suh, 2016). Another peptide named ecumicin, produced by
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Nonomuraea spp. MJM5123 and composed of 13 amino acids, also showed promising anti-TB activity
against MDR and XDR MTb, with MIC values ranging from 0.16 to 0.62 μM. The minimal bactericidal
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concentration (MBC) was 1.5 μM (Lee and Suh, 2016).
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Sansanmycins are members of uridylpeptide family produced by the soil bacterium Streptomyces
spp. These uridylpeptides are potents and selective anti-mycobacterials involved in inhibition of
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peptidoglycan biosynthesis (Tran et al., 2016). Teixobactin is a recently discovered anti-mycobacterial
peptide isolated from Eleftheria terrae, a soil microorganism. The mechanism of action was identified as
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inhibition of peptidoglycan biosynthesis, though, noteworthy, teixobactin-resistant strains of M.

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tuberculosis could not be generated (Ling et al., 2015).

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3.9. Quinones and terpenes
In 2016, Jyoti et al. reported the effects of an extract of Artemisia capillaris on the in vitro
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susceptibility of MTb. This plant is native to Central and Southeast Asia, particularly Korea, and is used
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as an antimicrobial agent. Two compounds from this extract were identified as active against MTb strains
using bioassay-guided fractionation, ursolic acid (UA) and hydroquinone (HQ), with a MIC of 12.5
μg/mL against the susceptible strains, and of 12.5-25 μg/mL against MDR/XDR strains. This group also
investigated the mechanism by which UA may exert its anti-MTb activity (Jyoti et al., 2016). In strain
MTb H37Ra, UA decreased mycolic acid biosynthesis in a dose-dependent manner as determined by
quantitative LC/MS/MS. This compound is a branched long-chain fatty acid that makes up to 60% of the
outer cell wall of Mycobacterium. By inhibiting biosynthesis of mycolytic acid the bacterial cell wall
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cannot be formed and this causes Mycobacterium cell death. Electron microscopy further confirmed that
UA had effects on both the cell wall and the intracellular content of H37Ra (Jyoti et al., 2015).
In 2013, Metha et al. showed that extracts of Citrullus colocynthis (L.) Schrad. (Cucurbitaceae),
known commonly as bitter apple, a medicinal plant from India used to treat bacterial infections, including
tuberculosis and other respiratory diseases, had activity against MTb (Mehta et al., 2013). In this study, a
methanol extract of the ripe fruits exhibited activity against MTb strains with a MIC ≤ 62.5 µg/ml. One
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fraction (FC III) of this extract showed a MIC of 31.2 µg/mL against strain MTb H37Rv, and other
fractions also inhibited 16 clinical isolates of MTb, including 7 wild type, 8 MDR-TB, 1 XTB and 2 non-
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TB Mycobacterium strains with MICs in the range of 50-125, 31.2-125 and 62.5-125 µg/mL, respectively.
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Interestingly, the active compound identified from fraction FC III was UA, though other terpenes were
also identified as cucurbitacin E 2-O-β-D-glucopyranoside and cucurbitacin I 2-O-β-D-glucopyranoside

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from fraction FC IX. Ursolic acid and cucurbitacin E 2-O-β-D-glucopyranoside were identified as the
main chemical constituents active against MTb H37Rv (MICs 50 and 25 µg/ml, respectively), as well as
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against the clinical isolates (Mehta et al., 2013).

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In a publication by Uc-Cachón et al. (2014), naphthoquinones with anti-MTb activity were
isolated from Diospyros anisandra, a native plant from the Yucatan peninsula used in traditional Mayan
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medicine. These compounds have a naphthalene skeleton substituted by ketone groups in positions C1
and C2 (1,2-naphthoquinones) or positions C1 and C4 (1,4-naphthoquinones), and are found as

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monomers, dimers, trimers or tetramers (Uc-Cachón et al., 2014). Naphthoquinones have a wide variety
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of biological activities, including antibacterial, antifungal, antiparasitic, antiviral, antiinflammatory and
cytotoxic effects. In this study, stem bark extracts of Diospyros anisandra were active against MTb
strains, and 3 monomeric and 5 dimeric naphthoquinones were isolated, identified and tested. Plumbagin
and its dimers maritinone and 3,30-biplumbagin showed the highest activity against both susceptible and
MDR-TB strains with a MIC of 1.56-3.33 mg/mL. Only maritinone and 3,30-biplumbagin showed no
toxicity against normal eukaryotic cells, and had 32 times more activity against MDR-TB strains. In terms
of mechanism of action, it has been shown that naphthoquinones can target the electron transport chain of
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Mycobacterium because they are structurally similar to menaquinone. In addition, they also may inhibit
menaquinone biosynthesis thereby interfering with electron transport and cellular respiration (Uc-Cachón
et al., 2013).
4. Case study: traditional Chinese medicine
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In traditional Chinese medicine (TCM), many herbal formulas have been used as adjunctive
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therapy, along with conventional TB chemotherapy, to manage MDR-TB. Some clinical trials have
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shown that various TCM herbal formulas can enhance the immune system, reduce adverse events
observed with conventional TB chemotherapy, improve the overall quality of life, and decrease the level
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of MTb in sputum culture (Jiang et al., 2015). One systematic review and meta-analysis analyzed 20
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clinical trials involving 1823 TB patients from China (Jiang et al., 2015). This review concluded that
adjunct therapy with TCM herbal formulas and TB chemotherapy significantly (p < 0.001) enhanced the
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treatment success and improved radiological findings. However, subjects who received TCM herbals in
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combination with chemotherapy had similar relapse rates; though the incidence of adverse events was
lower (Jiang et al., 2015). These data suggest that TCM herbal medicines may improve the overall
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treatment and recovery of TB.
A second systematic review and meta-analysis assessed the effects of TCMs in combination with
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TB chemotherapy in 30 randomized clinical trials (RCTs) involving 3374 participants with a diagnosis of
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MDR-TB (Wang et al., 2015). This review concluded that the quality of the clinical trials in the analysis
was generally poor in terms of risk of bias. It further suggested again that TCM plus chemotherapy was
more effective on the conversion rate of sputum as compared with chemotherapy alone. The study
showed that, when compared with chemotherapy only, a benefit in MDR-TB patients was observed on the
rate of reduction of lung lesions (in 7 studies), cavity closure rate (5 studies), reduced relapse rate (4
studies) and reduced abnormal liver function tests (14 studies) when TCM plus chemotherapy was used.
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No serious adverse event was reported in any of the study. The authors further suggested that, considering
the positive results, further robust clinical trials are warranted (Wang et al., 2015).
Beyond the clinical trials, one rodent study by Lu et al. (2013) investigated the effects of the
traditional Chinese herbal medicines Radix Ranunculi Ternati, Radix Sophorae Flavescentis, Prunella
vulgaris L. and Stellera chamaejasme L. on immunity in a rat model of MDR-TB. Treatment of the
animals with the TCM herbal remedies significantly changed the levels of serum IFN-γ (p < 0.05). RT-
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PCR analysis showed a statistically significant increase in the mRNA levels of IFN-γ and IL-12, and a
significant decrease in the mRNA levels of IL-4 and IL-10 (p < 0.05). In summary, this study showed that
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treatment with TCM herbs increased cellular-mediated immunity in a MDR-TB rodent model (Lu et al.,
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2013).
In addition, an in vitro study performed by Nam et al. showed that (-)-deoxypergularine (DPX),
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an alkaloid extracted from the dried roots of the plant Cynanchum atratum (known as Bai Wei in TCM)
showed activity against MDR-TB (Nam et al., 2016). The compound inhibited the growth of both
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susceptible and MDR-TB strains with a MIC of 12.5 µg/mL, with excellent activity against XDR-TB at
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12.5 µg/mL. In a checkerboard assay, the combination of DPX and rifampin was synergistic in the MTb
strain H37Ra, as was isoniazid plus DXP. In combination with streptomycin or ethambutol, the results
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were equivocal. Unfortunately, no checkerboard assays were performed on the XDR-resistant strains
(Nam et al., 2016).

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4.1. In vitro evidence
Tuberculosis or ’the white plague’, as people named it due to high fatal rate, even today presents
one of the leading cause of motality with 9 million cases of active TB and 1.3 million deaths occurring
every year (Hussain at al., 2014). Significant factors such as specific cell wall composition, dormant cells,
long lasting therapy and inproper use of the first- and second-line drugs are related to continously
increasing incidence of the multi-drug resistant (MDR) strains. Therefore, modern science is in constant
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search for novel alternatives in treating this infectious disease, especially those from natural sources
which may have shorter treatment regimes and be effective with fewer side-effects. In these
investigations, researchers mostly rely on the data obtained from traditional medicine practitioners. One
of the first known studies in this route was the efficacy of garlic as antitubercular therapy, carried out in
1912 by Dr. Minchin. He performed anti-TB treatments on his patients by an inhaler mask containing a
sponge soaked in garlic juice and reported that, in certain individuals, the drug was active against the
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pathogen (Dini et al., 2011). In the last decades, the studies have focused to the efficacy of
phytochemicals against multi-drug resistant isolates of Mycobacterium tuberculosis, thus providing
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promising results on the effectiveness of plant products against Mycobacterium.
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Garlic was demonstrated to possess antimycobacterial activity in many studies, where allicin was
confirmed to be the carrier of this activity in the study of Gupta and Viswanathan (Gupta and
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Viswanathan, 1955). They found that this compound acts in synergistic manner with antibiotics
streptomycin and chloramphenicol against M. tuberculosis. The same synergism was not detected when
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antitubercular drugs were combined with garlic extract, thus pointing to the allicin efficacy (Abbruzzese
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et al., 1987). Further studies on this subject confirmed garlic efficiency against various MTb strains,
including MDR ones (Delaha and Garagusi, 1985; Ratnakar and Murthy, 1996; Gupta et al., 2010;
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Hannan et al., 2011). The most recent study of (Rajani et al., 2015), who investigated ethanol extract of
garlic against 48 MDR and one reference strains (H37Rv) of MTb showed MIC values in the range of 0.5-
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2.0 mg/ml. Another plant of the Allium genus, shallot (Allium ascalonicum L.), was investigated for
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activity against MTb in the study of (Mansour et al., 2009). Its ethyl acetate extract exhibited activity
against all of the ten tested clinical isolates of MTb at concentration of 500 µg/mL.
Nine plants used in Mexican traditional medicine to treat tuberculosis and other respiratory
diseases were used for making hexane, methanol, chloroform and water extracts, which were further
evaluated for antimycobacterial activity (Camacho‐Corona et al., 2008). Among the tested extracts, the
activity was shown by hexane (Citrus aurantifolia, C. sinensis, Foeniculum vulgare, Olea europaea), two
chloroform (Larrea tridentata, Nasturtium ofﬁcinale) and one methanol (Musa acuminata) extracts.
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Nasturtium ofﬁcinale chloroform extract exhibited the most prominent activity against both reference and
MDR strains (MICs were 100 µg/mL and < 100 µg/mL, respectively). Other extracts showing activity
against these strains were Foeniculum vulgare and Olea europaea hexane extracts, which exhibited
efficacy against all the resistant MTb variants at concentrations lower than 100 µg/mL.
Study by León-Díaz (2010) showed that hexane extract of Aristolochia taliscana, the herb used in
Mexican traditional medicine, presents an important source of antimycobacterial compounds. This extract
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was tested against a wide range of mycobacteria including standard strain (H37Rv), four mono-resistant
H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria.
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Bioguided fractionation of the obtained extract led to the isolation of the neolignans licarin A, licarin B
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and eupomatenoid-7, which all demonstrated antimycobacterial activity at very low concentrations (3.25-
50.00 µg/mL). Among them, the most prominent action was observed for licarin A, which was active at
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6.25 µg/mL even against MDR isolate resistant to first- and second-line antibiotics (León-Díaz et al.,
2010). Gupta et al. (2010) investigated activity of aqueous extracts of Acalypha indica and Adhatoda
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vasica leaves, bulbs of Allium cepa, cloves of Allium sativum and pure gel of Aloe vera leaves against
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MDR strains of MTb. All extracts were be effective against MDR isolates and drug-susceptible reference
strain H37Rv.
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Among the tested acetone, ethanol and aqueous extracts obtained from 5 plants (Acorus calamus
L. rhizome, Andrographis paniculata Nees. leaves, Ocimum sanctum L. leaves, Piper nigrum L. seeds
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and Pueraria tuberosa DC. tuber), only P. nigrum acetone extract showed to possess antimycobacterial
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activity (Birdi et al., 2012). In the study of Anthony et al. (2012), butanol extracts of Alstonia scholaris
fruits, flowers, bark and leaves were tested for efficacy against one standard strain (H37Rv), one clinical
isolate sensitive to antibiotics, and one MDR clinical strain. The results pointed to significant efficacy of
bark and leaf extracts against MDR strain at 100 µg/mL, while at 500 µg/mL all extracts showed
inhibitory action against all tested strains. Among them, the highest activity was reported for bark extract
of Alstonia scholaris, which showed inhibition of 47.40, 51.46 and 73.09% against standard, clinical
sensitive and clinical MDR strains, respectively.
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Seven mangrove plants (Ceriops decandra, Aegiceras corniculatum, Excoecaria agollacha,
Avicennia officinalis, Rhizophora mucronata, Suaeda monoica and Sesuvium portulacastrum) were
collected and their hexane and methanol extracts were tested for antimycobacterial activity (Prabhu,
2014). The assys were carried against one standard, one clinical strain sensitive to drugs and one strain of
Mycobacterium tuberculosis resistant to streptomycin, isoniazid, rifampicin and ethambutol. Hexane
extracts of all plants failed to exert antimycobacterial activity, while methanol extracts of E. agollacha,
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followed by those extracted from A. corniculatum and A. officinalis exhibited significant activity at
concentrations of 500 µg/mL.
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In another study, fresh leaves of Taxus baccata, Senna alata, Andrographis paniculata, Adhatoda
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vasica, Acalypha indica and Aloe vera were extracted with water (ratio 1:1) and investigated against three
MTb strains, including one MDR strain (DKU-156). The results showed inhibition of the treated MDR
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strain by all tested extracts at concentrations 2, 4 and 6% (Bernaitis et al., 2013). Among the tested
extracts, T. baccata showed the highest potency considering percentage of bacterial growth reduction on
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LJ (Lowenstein Jensen) agar.

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In the study of Deveci et al. (2013), a total of 57 isolates including 17 MDR strains were
investigated for sensitivity to Ankaferd Blood Stopper®, a mixture of plant extracts prepared from
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Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica and Vitis vinifera. The mixture
showed very significant antimycobacterial activity, with inhibitory concentrations ranging from < 1.37
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µg/mL to 21.88 µg/mL. Singh et al. (2013) investigated different solvent extracts of two plants, Urtica
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dioica and Cassia sophera, for antimycobacterial activity. They determined that the hexane extract of U.
dioica and methanol extract of C. sophera possessed this activity. Further testing of semi-purified
fractions of these two extracts showed significant inhibition of clinical MDR strains of MTb.
Gupta et al. (2014) investigated antimycobacterial activity of Alpinia galanga (L.) Willd. under
intracellular and in axenic (aerobic and anaerobic) conditions. Intracellular assay represented a model for
investigating the activity of the extracts against non-replicating dormant bacilli, characterized by the
switch from aerobic/microaerophilic to anaerobic respiratory pathways. Among the tested extracts
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(obtained by water, acetone and ethanol Soxhlet extraction), acetone and etanolic extracts were active in
all tested conditions at low concentrations (25, 50 and 100 µg/ml). Recently, similar investigation (in
axenic and intracelluler conditions) was carried out by Bhatter et al. (2016) who tested the efficacy of
acetone, ethanol and aqueous extracts of four plant species (Acorus calamus L. rhizome, Ocimum
sanctum L. leaves, Piper nigrum L. seeds and Pueraria tuberosa DC. tuber) against MTb H37Rv.
Acetone extract of P. nigrum showed the highest antimycobacterial activity by inhibiting the tested strain
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in aerobic, microaerophilic and anaerobic conditions. Also, water extract of P. tuberosa showed
significant activity under reduced oxygen conditions, which pointed to the importance of anaerobiosis for
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its efficacy.
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Antimycobacterial activity of aqueous extracts of selected Indonesian medicinal plants
(Andrographis paniculata, Annona muricata, Centella asiatica, Pluchea indica and Rhoeo spathacea)
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was investigated in the study of Radji et al. (2015). Their results showed that Pluchea indica and Rhoeo
spathacea ehxibited promising antimycobacterial activity against a MDR strain of Mycobacterium

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tuberculosis, by inhibiting its growth at concentrations of 2.5 and 5 mg/mL.

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Another recent study on the plant efficacy against mycobacteria was the one performed by
Johanpour et al. (2015). They tested antimycobacterial activity of the ethanol extract from six Iranian
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medicinal plants against six clinical isolates (2 of them were MDR). The results pointed to significant
activity of Peganum harmala and Punica granatum extracts. Owing to the fact that the assay was carried
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out using disc diffusion method, high concentrations (100 and 200 mg/mL) were determined to be active.
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Considering sensitive isolates, the inhibition zones of the P. harmala extract at higher concentration
corresponded to those obtained by rifampin and isoniazid. Another study showed the activity of methanol,
ethyl acetate and n-hexane extracts from plant material of Euphorbia hirta, a medicinal plant used in
India for the treatment of many respiratory disorders (asthma, cough and various acute/chronic respiratory
infections). Among the tested extracts, ethyl acetate extract showed the highest activity against MTb
H37Rv, with concentration of 500 µg/mL reducing microbial growth to 35.27% in comparison with the
untreated, control value (Rajasekar et al., 2015).
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Finally, four clinical isolates including two MDR and two sensitive strains to rifampin and
isoniazid were used to investigate the antimycobacterial activity of the Peganum harmala hydro-alcoholic
seed extract. All tested strains, including the MDR ones, showed sensitivity to this extract (Davoodi et al.,
2015).
5. Conclusions
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The urgent need for development of new drugs to reduce the global burden of TB has greatly
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stimulated the exploration of traditional knowledge as source of novel and effective phytotherapeutic
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agents. Worldwide, many plant species have been and continue to be used in various traditional healing
systems, as well as marine organisms and fungi, thus representing a nearly unlimited source of active
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ingredients.
Noteworthy, besides their antimycobacterial activity, natural products can be useful in adjuvant
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therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse
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effects and to reverse mycobacterial multi drug-resistance, the latter an emerging and very critical topic
because of the genetic plasticity and environmental adaptability of Mycobacterium. Probably, the wide
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use of some traditional herbal remedies in the treatment of tuberculosis may be indicative of their efficacy
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and, above all, safety. Not least, natural products can also be used as a template for the development of
new scaffolds of drugs.

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In any case, crude natural product extracts are complex mixtures of hundreds of different
compounds that may be synergistically active once administered. Therefore, discovery and development
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of new pure products involve isolation, purification and identification of target compounds from complex
crude extracts is sometimes a major drawback in natural products research. Not least, even if some natural
products have still been investigated in clinical trials, the validation of their efficacy and safety as
antituberculosis agents is far from being reached, and, hence, according to an evidence-based approach,
more high-level randomized clinical trials are urgently needed.
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References
Abbruzzese, M.R., Delaha, E.C., Garagusi, V.F., 1987 Absence of antimycobacterial synergism between
garlic extract and antituberculosis drugs. Diagn. Microbiol. Infect. Dis. 8 (2), 79-85.
Adhvaryu, M., Vakharia, B., 2011. Drug-resistant tuberculosis: emerging treatment options. Clin.
Pharmacol. 3, 51-67.
Ahmad, I., Aqil, F., Owais, M., 2006. Modern Phytomedicine: Turning Medicinal Plants into Drugs.
USA: Wiley.
T
Ahmed, H.M., 2016. Ethnopharmacobotanical study on the medicinal plants used by herbalists in
Sulaymaniyah Province, Kurdistan, Iraq. J. Ethnobiol. Ethnomed. 12, 8.
IP
Ahuja, S., Ahuja, S., Ahuja, U., 2015. Nirgundi (Vitex negundo) – Nature’s Gift to Mankind. Asian
Agrihist. 19, 5-32.
CR
Alvin, A., Miller, K.I., Neilan, B.A., 2014. Exploring the potential of endophytes from medicinal plants
as sources of antimycobacterial compounds. Microbiol Res. 169 (7-8), 483-95.
Antony, M., James, J., Misra, C.S., Sagadevan, L.D.M., Veettil, A.T., Thankamani, V., 2012. Anti
mycobacterial activity of the plant extracts of Alstonia scholaris. Int. J. Curr. Pharm. Res. 4, 40-
US
422.
Arai, M., Yamano, Y., Setiawan, A., Kobayashi, M., 2014. Identification of the Target Protein of
Agelasine D, a Marine Sponge Diterpene Alkaloid, as an Anti-dormant Mycobacterial Substance.
AN
Chem. Bio.Chem. 15(1), 117-123
Arya, V., 2011. A Review on Anti-Tubercular Plants. Int. J. Phar.Tech Res. 3 (2), 872-880.
Atanasov, A.G., Waltenberger, B., Pferschy-Wenzig, E.M., Linder, T., Wawrosch, C., Uhrin, P., Temml,
V., Wang, L., Schwaiger, S., Heiss, E.H., Rollinger, J.M., Schuster, D., Breuss, J.M., Bochkov,
M
V., Mihovilovic, M.D., Kopp, B., Bauer, R., Dirsch, V.M., Stuppner, H., 2015. Discovery and
resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv.
33(8), 1582-614.
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Ayyanar, M., Ignacimuthu, S., 2008. Medicinal uses and pharmacological actions of five commonly used
Indian medicinal plants: a mini-review. Iran. J. Pharmacol. Ther. 7,107-14.
Batugal, P.A., Kanniah, J., Young, L.S., Oliver, J.T., 2004. Medicinal Plants Research In Asia. Serdang,
PT
Selangor DE, Malaysia: International Plant Genetic Resources Institute – Regional Office for
Asia, the Pacific and Oceania (IPGRI-APO);
Bedi, R.S., 2005. Management of tuberculosis in special situations. Lung India 22, 138-41.
CE
Bernaitis, L., Shenoy, V.P., Ashok, M., Nath, M., Shenoy, R.P., 2013. Effects of selective medicinal
plants against multi drug resistance Mycobacterium tuberculosis strains. Res. J. Pharm. Biol.
Chem. Sci. 4 (3), 812-7.
Bhatter, P.D., Gupta, P.D., Birdi, T.J., 2016. Activity of Medicinal Plant Extracts on Multiplication of
AC
Mycobacterium tuberculosis under Reduced Oxygen Conditions Using Intracellular and Axenic
Assays. Int. J. Microbiol. 2016, 8073079.
Birdi T, D'souza D, Tolani M, Daswani P, Nair V, Tetali P, Toro J.C. Hoffner S., 2012. Assessment of the
activity of selected Indian medicinal plants against Mycobacterium tuberculosis: a preliminary
screening using the Microplate Alamar Blue Assay. European J. Med. Plants. 2 (4), 308-323.
Bunalema, L., 2010. Anti-mycobacterial activity and acute toxicity of Erythrina abyssinica, Cryptolepis
sanguinolenta and Solanum incanum Uganda: Makerere University Kampala.
Camacho‐Corona, M.R., Ramírez‐Cabrera, M.A., Santiago, O.G., Garza‐González, E., Palacios, I.P.,
Luna‐Herrera, J., 2008. Activity against drug resistant‐tuberculosis strains of plants used in
Mexican traditional medicine to treat tuberculosis and other respiratory diseases. Phytother. Res.
22 (1), 82-5.
52
ACCEPTED MANUSCRIPT
Cardona, P., Ruiz-Manzano, J., 2004. On the nature of Mycobacterium tuberculosis-latent bacilli. Eur.
Respir. J. 24 (6), 1044-51.
Chandra, S., Rawat, D.S., 2015. Medicinal plants of the family Caryophyllaceae: a review of ethno-
medicinal uses and pharmacological properties. Integr. Med. Res. 4(3), 123-31.
Chiang, C.Y., Centis, R., Migliori, G.B., 2010. Drug‐resistant tuberculosis: past, present, future.
Respirology 15 (3), 413-32.
Coronado-Aceves, E.W., Sánchez-Escalante, J.J., López-Cervantes, J., Robles-Zepeda, R.E., Velázquez,
C., Sánchez-Machado, D.I., Garibay-Escobar, A., 2016. Antimycobacterial activity of medicinal
plants used by the Mayo people of Sonora, Mexico. J. Ethnopharmacol. 190, 106-15.
Cragg, G.M., Newman, D.J., 2013. Natural products: a continuing source of novel drug leads. Biochim.
Biophys. Acta. 1830 (6), 3670-95.
T
Daletos, G., Ancheeva, E., Chaidir, C., Kalscheuer, R., Proksch, P., 2016. Antimycobacterial Metabolites
IP
from Marine Invertebrates. Archiv. Der Pharmazie. 349, 763-773
Davoodi, H., Ghaemi, E., Mazandarani, M., Shakeri, F., Javid, S., Klishadi, M., 2015. Anti-mycobacterial
and anti-inflammatory activity of Peganum harmala. J. Chem. Pharm. Res. 7 (4), 1611-6.
CR
Debnath, P.K., Chattopadhyay, J., Mitra, A., Adhikari, A., Alam, M.S., Bandopadhyay, S.K., Hazra, J.,
2012. Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic
management of pulmonary tuberculosis. J. Ayurveda Integr. Med. 3 (3), 141–149.
US
Delaha, E.C., Garagusi, V.F., 1985. Inhibition of mycobacteria by garlic extract (Allium sativum).
Antimicrob. Agents. Chemother. 27 (4), 485-486.
Deveci, A., Coban, A.Y., Tanrıverdi, Ç.Y., Acicbe, O., Taşdelen, F.N., Akgüneş, A., Ozatlı, D., Uzun,
M., Durupınar, B., 2013. In Vitro Effect of Ankaferd Blood Stopper®, a Plant Extract Against
AN
Mycobacterium tuberculosis Isolates. Mikrobiyol. Bul. 47 (1),71-8.
Dhanabal, S.P., Lall, N., Pavithra, N., Chaitanya, M.V.N.L. 2015. Natural products as an important leads
for discovery of new antitubercular agents: A review. Int. J. Pharm. Pharm. Sci. 7(10), 2-7.
M
Diacon, A.H., Pym, A., Grobusch, M., Patientia, R., Rustomjee, R., Page-Shipp, L., Pistorius, C., Krause,
R., Bogoshi, M., Churchyard, G., Venter, A., Allen, J., Palomino, J.C., De Marez, T., Van
Heeswijk, R.P., Lounis, N., Meyvisch, P., Verbeeck J., Parys, W., De Beule, K., Andries, K., Mc
ED
Neeley, D.F., 2009. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl. J.
Med. 360 (23), 2397-405.
Dini, C., Fabbri, A., Geraci, A., 2011. The potential role of garlic (Allium sativum) against the multi-drug
PT
resistant tuberculosis pandemic: a review. Ann Ist Super Sanita. 47 (4), 465-73.
Dong, M., Pfeiffer, B., Altmann, K.H. 2017. Recent developments in natural product-based drug
discovery for tuberculosis. Drug Discov. Today. 22(3), 585-591.
Faleyimu, O.I., Akinyemi, O., Adejoba, O.R., 2009. Herbal solution to the treatment of tuberculosis
CE
infection in Kaduna south local government, Kaduna, Nigeria. J. Environ. Ext. 8(3), 40-3.
Farshidpour, M., Ebrahimi, G., Mirsaeidi, M., 2013. Multidrug-resistant tuberculosis treatment with
linezolid-containing regimen. Int. J. Mycobacteriol. 2 (4), 233-236.
AC
Ganihigama, D.U., Sureram, S., Sangher, S., Hongmanee, P., Aree, T., Mahidol, C., Ruchirawat, S.,
Kittakoop, P., 2015. Antimycobacterial activity of natural products and synthetic agents:
pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant
isolates of Mycobacterium tuberculosis. Eur. J. Med. Chem. 89,1-12.
Gautam, H.A., Sharma, R., Rana, A.C., 2012. Review on herbal plants useful in tuberculosis. Int. Res. J.
Pharm. 3 (7), 64-7.
Gautam, R., Saklani, A., Jachak, S.M., 2007. Indian medicinal plants as a source of antimycobacterial
agents. J. Ethnopharmacol. 110 (2), 200-34.
Ghanashyam, B., 2016. Changing the game for multidrug-resistant tuberculosis. Lancet. 387 (10024),
1149-50.
Green, E., Samie, A., Obi, C.L., Bessong, P.O., Ndip, R.N., 2010. Inhibitory properties of selected South
African medicinal plants against Mycobacterium tuberculosis. J. Ethnopharmacol. 130 (1),151-7.
53
ACCEPTED MANUSCRIPT
Gupta P, Bhatter P, D’souza D, Tolani M, Daswani P, Tetali P, Birdi T., 2014. Evaluating the anti
Mycobacterium tuberculosis activity of Alpinia galanga (L.) Willd. axenically under reducing
oxygen conditions and in intracellular assays. BMC Complement. Altern. Med. 4, 14, 84.
Gupta, K., Viswanathan, R., 1955. Combined Action of Streptomycin and Chloramphenicol with Plant
Antibiotics against Tubercle Bacilli. Part I: Streptomycin and Chloramphenicol with
Cepharanthine. Part II: Streptomycin and Allicin. Antibiot. Chemother. 5 (1), 24-7.
Gupta, R., Thakur, B., Singh, P., Singh, H.B., Sharma, V.D., Katoch, V.M., Chauhan, S.V., 2010. Anti-
tuberculosis activity of selected medicinal plants against multi-drug resistant Mycobacterium
tuberculosis isolates. Indian J. Med. Res. 131, 809-13.
Hannan, A., Ikram Ullah, M., Usman, M., Hussain, S., Absar, M., Javed, K., 2011. Anti-mycobacterial
activity of garlic (Allium sativum) against multi-drug resistant and non-multi-drug resistant
T
Mycobacterium tuberculosis. Pak. J. Pharm. Sci. 24, 81-5.
IP
Holtz, T., Cegielski, J., 2007. Origin of the term XDR-TB. Eur. Respir J. 30 (2), 396.
Holzgrabe, U., 2015. New griselimycins for treatment of tuberculosis. Chem. Biol. 22 (8), 981-2.
Hussain, S., Haq, A., Nisar, M., Ahmad, T., Bhardwaj, P., 2014. Evaluation of in-vitro anti-mycobacterial
CR
activity and isolation of active constituents from Crocus sativus L. (Iridaceae). Asian J. Med.
Pharma. Res. 4, 130-5.
Jahanpour, S., Ghazisaidi, K., Davoodi, H., Mazandarani, M., Samet, M., Jahanpour, N., Ghaemi E.A.,
US
2015. Antimicrobial Effects of Folk Medicinal Plants From the North of Iran Against
Mycobacterium tuberculosis. Arch. Pediatr. Infect. Dis. 3 (1 TB), e18098.
Jiang, R.H., Xu, H.B., Fu, J., 2015. Outcomes of Chinese herb medicine for the treatment of multidrug-
resistant tuberculosis: a systematic review and meta-analysis. Complement. Ther. Med.
AN
23(4):544-54.
Jyoti, M.A., Nam, K.W., Jang, W.S., Kim, Y.H., Kim, S.K., Lee, B.E., Song, H.Y., 2016.
Antimycobacterial activity of methanolic plant extract of Artemisia capillaris containing ursolic
M
acid and hydroquinone against Mycobacterium tuberculosis. J. Infect. Chemother. 22 (4), 200-8.
Jyoti, M.A., Zerin, T., Kim, T.H., Hwang, T.S., Jang, W.S., Nam, K.W., Song, H.Y., 2015. In vitro effect
of ursolic acid on the inhibition of Mycobacterium tuberculosis and its cell wall mycolic acid.
ED
Pulm. Pharmacol. Ther. 33, 17-24.

Kaufmann, S., Evans, T.G., Hanekom, W.A., 2015. Tuberculosis vaccines: time for a global strategy. Sci.
Transl. Med. 7, 276fs8.
PT
Kinghorn, A.D., Pan, L., Fletcher, J.N., Chai, H., 2011. The relevance of higher plants in lead compound
discovery programs. J. Nat. Prod. 74 (6), 1539-55.
Koul, A., Arnoult, E., Lounis, N., Guillemont, J., Andries, K., 2011.The challenge of new drug discovery
for tuberculosis. Nat. 469, 483-90.
CE
Kumar, P., Singh, A., Sharma, U., Singh, D., Dobhal, M., Singh, S., 2013. Anti-mycobacterial activity of
plumericin and isoplumericin against MDR Mycobacterium tuberculosis. Pulm. Pharmacol. Ther.
26 (3), 332-5.
AC
Lakshmanan, D., Werngren, J., Jose, L., Suja, K.P., Nair, M.S., Varma, R.L., Mundayoor, S., Hoffner, S.,
Kumar, R.A. 2011. Ethyl p-methoxycinnamate isolated from a traditional anti-tuberculosis
medicinal herb inhibits drug resistant strains of Mycobacterium tuberculosis in vitro. Fitoterapia.
82 (5), 757-61.
Lall, N., Meyer, J.J.M., 1999. In vitro inhibition of drug-resistant and drug-sensitive strains of
Mycobacterium tuberculosis by ethnobotanically selected South African plants. J.
Ethnopharmacol. 66 (3), 347-54.
Lalvani, A., Sridhar, S., Von Reyn, C.F., 2013. Tuberculosis vaccines: time to reset the paradigm?
Thorax. 68 (12),1092-4.
Lawal, I.O., Grierson, D.S., Afolayan, A.J., 2014. Phytotherapeutic Information on Plants Used for the
Treatment of Tuberculosis in Eastern Cape Province, South Africa. Evid. Based Complement.
Alternat. Med. 2014, 735423.
54
ACCEPTED MANUSCRIPT
Lee, H., Suh, J.W., 2016. Anti-tuberculosis lead molecules from natural products targeting
Mycobacterium tuberculosis ClpC1. J. Ind. Microbiol. Biotechnol. 43 (2-3), 205-12.
Lee, M., Cho, S.N., Barry, C.E. 3rd, Song T, Kim, Y., Jeong, I., 2015. Linezolid for XDR-TB--Final
Study Outcomes. N. Engl. J. Med. 373 (3), 290-1.
Leitão, F., Leitão, S.G., De Almeida, M.Z., Cantos, J., Coelho, T., Da Silva, PE., 2013. Medicinal plants
from open-air markets in the State of Rio de Janeiro Brazil as a potential source of new
antimycobacterial agents. J. Ethnopharmacol. 149 (2), 513-21.
León-Díaz, R., Meckes, M., Said-Fernández, S., Molina-Salinas, G.M., Vargas-Villarreal, J., Torres, J.,
Luna-Herrera, J., Jiménez-Arellanes, A., 2010. Antimycobacterial neolignans isolated from
Aristolochia taliscana. Mem. Inst. Oswaldo Cruz. 105 (1), 45-51.
Ling, L.L., Schneider, T., Peoples, A.J., Spoering, A.L., Engels, I., Conlon, B.P., Mueller, A., Schäberle,
T
T.F., Hughes, D.E., Epstein, S., Jones, M., Lazarides, L., Steadman, V.A., Cohen, D.R., Felix,
IP
C.R., Fetterman, K.A., Millett, W.P., Nitti, A.G., Zullo, A.M., Chen, C., Lewis, K., 2015. A new
antibiotic kills pathogens without detectable resistance. Nat. 517 (7535), 455-459.
Liu, Q., Garner, P., Wang, Y., Huang, B., Smith, H., 2008. Drugs and herbs given to prevent
CR
hepatotoxicity of tuberculosis therapy: systematic review of ingredients and evaluation studies.
BMC Public Health 8, 365.
Lu, J., Ye, S., Qin, R., Deng, Y., Li, C.P., 2013. Effect of Chinese herbal medicine extracts on cell-
US
mediated immunity in a rat model of tuberculosis induced by multiple drug-resistant bacilli. Mol.
Med. Rep. 8 (1), 227-32.
Maarisit, W., Abdjul, D.B., Yamazaki, H., Kato, H., Rotinsulu, H., Wewengkang, D.S., Sumilat, D.A.,
Kapojos, M.M., Ukai, K., Namikoshi, M., 2017. Anti-mycobacterial alkaloids, cyclic 3-alkyl
AN
pyridinium dimers, from the Indonesian marine sponge Haliclona sp. Bioorg Med Chem Lett.
pii: S0960-894X(17)30564-4.
Madikizela, B., 2014. Pharmacological evaluation of South African medicinal plants used for treating
M
tuberculosis and related symptoms South Africa: University of KwaZulu-Natal.

Mangtani, P., Abubakar, I., Ariti, C., Beynon, R., Pimpin, L., Fine, P.E.M., Rodrigues L.C., Smith, P.G.,
Lipman, M., Whiting, P.F., Sterne, J.A., 2014. Protection by BCG vaccine against tuberculosis: a
ED
systematic review of randomized controlled trials. Clin. Infect. Dis. 58 (4), 470-480.
Mansour, A., Sepideh, S., Mohammad, H., 2009. Antimycobacterial activity of partial purified extract of
Allium ascalonicum. Jundishapur J. Microbiol. 2 (40), 144-147.
PT
Mariita, M.A.R., 2006. Efficacy of medicinal plants used by communities around Lake Victoria
Region and the Samburu against mycobacteria, selected bacteria and Candida albicans
Kenya: Kenyatta University.
Masjedi, M., Tabarsi, P., Chitsaz, E., Baghaei, P., Mirsaeidi, M., Amiri, M.V., Farnia, P., Javanmard, P.,
CE
Mansouri, D., Velayati, A.A., 2008. Outcome of treatment of MDR-TB patients with standardised
regimens, Iran, 2002–2006. Int. J. Tuberc. Lung. Dis. 12 (7), 750-5.
Masjedi, M.R., Farnia, P., Sorooch, S., Pooramiri, M.V., Mansoori, S.D., Zarifi, A.Z., Velayati, A.A.,
AC
Hoffner, S., 2006. Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran. Clin.
Infect. Dis. 43(7):841-7.
Masjedi, M.R., Tabarsi, P., Marjani, M., Shiva, P.B., Nasehi, M., Gooya, M.M., Farnia, P., Velayati A.A.,
2013. Management of MDR-TB: Review of Iran's Experience. Tanaffos 12 (1),6-15.
Mativandlela, S.P.N., Lall, N., Meyer, J.J.M., 2006. Antibacterial, antifungal and antitubercular activity
of (the roots of) Pelargonium reniforme (CURT) and Pelargonium sidoides (DC) (Geraniaceae)
root extracts. S. Afr. J. Bot. 72, 232-7.
Mehta, A., Srivastva, G., Kachhwaha, S., Sharma, M., Kothari, S., 2013. Antimycobacterial activity of
Citrullus colocynthis (L.) Schrad. against drug sensitive and drug resistant Mycobacterium
tuberculosis and MOTT clinical isolates. J. Ethnopharmacol. 149 (1), 195-200.
Mehta, P.K., King, C.H., White, E.H., Murtagh, J., Quinn, F.D., 1996. Comparison of in vitro models for
the study of Mycobacterium tuberculosis invasion and intracellular replication. Infect. Immun. 64
(7), 2673-2679.
55
ACCEPTED MANUSCRIPT
Meyer, J.J.M., Lall, N., Mathekga, A.D.M., Jäger, A.K., 2002. In vitro inhibition of drug-resistant and
drug-sensitive strains of Mycobacterium tuberculosis by Helichrysum caespititium. S. Afr. J. Bot.
68 (1), 90-93.
Millard, J., Ugarte-Gil, C., Moore, D.A. 2015. Multidrug resistant tuberculosis. BMJ 350, h882.
Mishra, R., Shukla, P., Huang, W., Hu, N., 2015. Gene mutations in Mycobacterium tuberculosis:
Multidrug-resistant TB as an emerging global public health crisis. Tuberculosis (Edinb) 95 (1), 1-
5.
Mohamad, S., Zin, N.M., Wahab, H.A., Ibrahim, P., Sulaiman, S.F., Zahariluddin, A.S., Noor, S.S., 2011.
Antituberculosis potential of some ethnobotanically selected Malaysian plants. J.
Nair, C.K.N., 1998. Medicinal plants of India. New Delhi: Nag Publishers.
T
Nam, K.W., Jang, W.S., Jyoti, M.A., Kim, S., Lee, B.E., Song, H.Y., 2016. In vitro activity of (-)-
IP
deoxypergularinine, on its own and in combination with anti-tubercular drugs, against resistant
strains of Mycobacterium tuberculosis. Phytomedicine 23 (5), 578-82.
Namita, P., Mukesh, R., 2012. Medicinal Plants used as antimicrobial agents: review. Int. Res. J. Pharm.
CR
3, 31-40.
Newman, D.J., Cragg, G.M., 2007. Natural Products as Sources of New Drugs over the Last 25 Years⊥. J.
Nat. Prod. 70 (3), 461–477.
US
Nguta, J.M., Appiah-Opong, R., Nyarko, A.K., Yeboah-Manu, D., Addo, P.G.A., 2015. Medicinal plants
used to treat TB in Ghana. Int. J. Mycobacteriol. 4 (2), 116-23.
Nguyen, L., 2016. Antibiotic resistance mechanisms in M. tuberculosis: an update. Arch. Toxicol. 90 (7),
1585-604.
AN
Nieves, K., Prudhomme, J., Le Roch, K.G., Franzblau, S.G., Rodríguez, A.D. (2016). Natural product-
based synthesis of novel anti-infective isothiocyanate-and isoselenocyanate-functionalized
amphilectane diterpenes. Bioorg. Med. Chem. Lett. 26 (3), 854-857
M
Ofukwu, R.A., Ayoola, A., Akwuobu, C.A., 2008. Medicinal plants used in the treatment of tuberculosis
in humans and animals by Idoma tribe of North-central Nigeria. Nig. Vet. J. 29 (2), 25-30.
Ogbole, O.O., Ajaiyeoba, E.O. 2010. Traditional Management of Tuberculosis in Ogun State of Nigeria:
ED
The Practice and Ethnobotanical Survey. Afr. J. Tradit. Complement. Altern. Med. 7 (1), 79–84.
Orodho, J.A., Okemo, P., Otieno, N., Kirimuhuzya, C.M.J.J., 2014. Indigenous knowledge of
communities around Lake Victoria Basin regarding treatment and management of tuberculosis
PT
using medicinal plants. Int. J. Med. Med. Sci. 6,16-23.

Parrish, N.M., Dick, J.D., Bishai, W.R., 1998. Mechanisms of latency in Mycobacterium tuberculosis.
Trends Microbiol. 6 (3), 107-12.
Paulson, T., 2013. Epidemiology: a mortal foe. Nat. 502, S2-S3.
CE
Poonam, K., Singh, G.S. 2009. Ethnobotanical study of medicinal plants used by the Taungya community
in Terai Arc Landscape, India. J. Ethnopharmacol. 123 (1), 167-76.
Prabhu, A., 2014. Antimycobacterial activity of certain mangrove plants against multi-drug resistant
AC
Mycobacterium tuberculosis. Asian J. Med Sci. 5(3), 54-7.

Radji, M., Kurniati, M., Kiranasari, A., 2015. Comparative antimycobacterial activity of some Indonesian
medicinal plants against multi-drug resistant Mycobacterium tuberculosis. J. App. Pharm. Sci. 5
(1), 019-022.
Rajani, S.D., Desai, P.B., Rajani, D.P., 2015. Anti-mycobacterial activity of garlic (Allium sativum)
against multi-drug resistant and reference strain of Mycobacterium tuberculosis. Int. J. Appl. Res.
1 (13), 767-770.
Rajasekar, T., Anbarasu, S., Manikkam, R., Joseph, J., Kumar V., 2015. Inhibitory activity of Euphorbia
hirta (Tawa-tawa) extracts against Mycobacterium tuberculosis and other non mycobacterial
pathogens. Der Pharma Chemica 7 (8), 213-216.
Ratnakar, P., Murthy, P.S., 1996. Preliminary studies on the antitubercular activity and the mechanism of
action of the water extract of garlic (Allium sativum) and its two partially purified proteins (Garlic
defensins?). Indian J. Clin. Biochem.11 (1), 37-41.
56
ACCEPTED MANUSCRIPT
Saganuwan, A.S. 2010. Some medicinal plants of Arabian Pennisula. Med. Plants Res. 4, 766-88.
Samad, A., Sultana, Y., Akhter, M.S., Aqil, M., 2008. Treatment of tuberculosis: use of active
pharmaceuticals. Recent Pat. Antiinfect. Drug Discov. 3, 34-44.
Samal, J., 2016. Ayurvedic management of pulmonary tuberculosis: A systematic review. J. Intercult.
Sansinenea, E., Ortiz, A., 2016. Antimycobacterial Natural Products from Marine Pseudopterogorgia
elisabethae. Curr. Org. Synth. 13 (4), 556-568.
Silva, J.P., Appelberg, R., Gama, F.M., 2016. Antimicrobial peptides as novel anti-tuberculosis
therapeutics. Biotechnol. Adv. 34 (5), 924-940.
Singh, R., Hussain, S., Verma, R., Sharma, P., 2013. Anti-mycobacterial screening of five Indian
medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica.
T
Asian Pac. J. Trop. Med. 6 (5), 366-71.
IP
Smith, C.B., Battin, M.P., Jacobson, J.A., Francis, L.P., Botkin, J.R., Asplund, E.P., Domek, G.J.,
Hawkins, B., 2004. Are there characteristics of infectious diseases that raise special ethical
issues?. Dev. World Bioeth. 4 (1), 1-16.
CR
Smith, I., 2003. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin.
Microbiol. Rev. 16 (3), 463-96.
Storey, C., Salem, J.I., 1997. Lay use of amazonian plants for the treatment of tuberculosis. Acta Amaz..
US
27 (3), 175-82.
Sureram, S., Senadeera, S.P., Hongmanee, P., Mahidol, C., Ruchirawat, S., Kittakoop, P., 2012.
Antimycobacterial activity of bisbenzylisoquinoline alkaloids from Tiliacora triandra against
multidrug-resistant isolates of Mycobacterium tuberculosis. Bioorg. Med. Chem. Lett. 22 (8),
AN
2902-5.
Tabuti, J.R.S., Kukunda, C.B., Waako, P.J., 2010. Medicinal plants used by traditional medicine
practitioners in the treatment of tuberculosis and related ailments in Uganda. J. Ethnopharmacol.
M
127 (1), 130-6.

Talavera, W., Miranda, R., Lessnau, K., Klapholz, A., 2001. Extrapulmonary tuberculosis. Tuberculosis:
current concepts and treatment, 2nd ed CRC Press, Inc, Boca Raton, Fla, pp. 139-90.
ED
Tascon, R., Soares, C., Ragno, S., Stavropoulos, E., Hirst, E., Colston, M., 2000. Mycobacterium
tuberculosis‐activated dendritic cells induce protective immunityin mice. Immunology 99 (3),
473–480.
PT
Tewari, U., Bahadur, A.N., Soni, P., 2015. Study of some Ethno Medicinal plants cultivated in Botanical
garden, Science College, Bilaspur (C.G.). Int. J. Adv. Res. Biol. Sci. 2, 353-9.
Tiemersma, E.W., Van der Werf M.J., Borgdorff, M.W., Williams, B.G., Nagelkerke, N.J., 2011. Natural
history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative
CE
patients: a systematic review. PloS one 6, e17601.

Tran, A.T., Watson, E.E., Pujari, V., Conroy, T., Dowman, L.J., Giltrap, A.M., Pang, A., Wong, W.R.,
Linington, R.G., Mahapatra, S., Saunders, J., Charman, S.A., West, N.P., Bugg, T.D., Tod, J.,
AC
Dowson, C.G., Roper, D.I., Crick, D.C., Britton, W.J., Payne, R.J., 2017. Sansanmycin natural
product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis. Nat
Commun. 8, 14414.
Uc-Cachón, A., Molina-Salinas, G., Said-Fernández, S., Méndez-González, M., Cáceres-Farfán, M.,
Borges-Argáez, R., 2013. A new dimeric naphthoquinone from Diospyros anisandra. Nat. Prod.
Res. 27 (13), 1174-8.
Uc-Cachón, A.H., Borges-Argáez, R., Said-Fernández, S., Vargas-Villarreal, J., González-Salazar, F.,
Méndez-González, M., Cáceres-Farfán, M., Molina-Salinas, G.M., 2014. Naphthoquinones
isolated from Diospyros anisandra exhibit potent activity against pan-resistant first-line drugs
Mycobacterium tuberculosis strains. Pulm. Pharmacol. Ther. 27 (1), 114-20.
Velayati, A.A., Farnia, P., Masjedi, M.R., 2012. Letter to Editor Recurrence after treatment success in
pulmonary multidrug-resistant tuberculosis: predication by continual PCR positivity. Int. J. Clin.
Exp. Med. 5 (3), 271-272.
57
ACCEPTED MANUSCRIPT
Viswanathan, V., Phadatare, A.G., Mukne, A., 2014. Antimycobacterial and Antibacterial Activity of
Allium sativum Bulbs. Indian J. Pharm. Sci. 76 (3), 256-61.
Wang, J.F., Dai, H.Q., Wei, Y.L., Zhu, H.J., Yan, Y.M., Wang, Y.H., Long, C.L., Zhong, H.M., Zhang,
L.X., Cheng, Y.X., 2010. Antituberculosis Agents and an Inhibitor of the para-Aminobenzoic
Acid Biosynthetic Pathway from Hydnocarpus anthelminthica Seeds. Chem. Biodivers. 7 (8),
046-53.
Wang, M., Guan, X., Chi, Y., Robinson, N., Liu, J.P., 2015. Chinese herbal medicine as adjuvant
treatment to chemotherapy for multidrug-resistant tuberculosis (MDR-TB): a systematic review
of randomised clinical trials. Tuberculosis 95, 364-72.
Warrier, P.K., 2002. Indian medicinal plants. Hyderabad: Orient Longman.
Wayne, L.G., Sohaskey, C.D., 2001. Nonreplicating persistence of Mycobacterium tuberculosis. Annu.
T
Rev. Microbiol. 55, 139-63.
IP
World Health Organization (WHO), 2013. The use of bedaquiline in the treatment of multidrug-resistant
tuberculosis: interim policy guidance.
World Health Organization (WHO), 2015. Global Tuberculosis Report.
CR
World Health Organization (WHO). 1998. Medicinal Plants in the South Pacific. Philippines: World
Health Organization, Regional Office for the Western Pacific in Manila.
World Health Organization (WHO). Global tuberculosis report 2016: World Health Organization; 2015.
US
Zhang, L., Li, R., Li, M., Qi, Z., Tian, J., 2015. In vitro and in vivo study of anti-tuberculosis effect of
extracts isolated from Ranunculi Ternati Radix. Sarcoidosis Vasc. Diffuse. Lung Dis. 31 (4), 336-
42.
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Highlights
Pulmonary tuberculosis is a human disease.

Multi-drug-resistant tuberculosis cause to an urgent need for discovery and development of new drugs to
reduce the global burden of this disease.
Many plant species have been and continue to be used in various traditional healing systems around the
world to treat tuberculosis.
Evidence-based approach, suggested for more high-level randomized clinical trials.
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Medicinal plants used in the treatment of

Article in Biotechnology advances · July 2017

Javad Sharifi-Rad Bahare Salehi

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Zorica Stojanović-Radić Patrick Valere Tsouh Fokou

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Biotransformation of a potent anabolic steroid, mibolerone, with Cunninghamella blakesleeana, C.

The user has requested enhancement of the downloaded file.

Medicinal plants used in the treatment of tuberculosis -

Javad Sharifi-Rad, Bahare Salehi, Zorica Z. Stojanović-Radić,

Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and

Javad Sharifi-Rada,*, Bahare Salehib*, Zorica Z. Stojanović-Radićc, Patrick Valere Tsouh

Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation

Traditional healing systems

strategy from ”Stop TB” to ”End TB“ strategy.

2. Traditional knowledge on plants used against tuberculosis

with considerable success in affected communities. Even though ethnobotanical and

Chinese, Ayurveda and so on.

pathogenesis accompanied by metabolic dysfunction (Dhatwagninasana): fluid, blood, muscle, adipose

administering herbs to protect the liver (Liu et al., 2008).

M. smegmatis) growing mycobacteria (Mariita, 2006). A. cepa anti-mycobacterial activities have

previously been reported (Arya, 2011).

of TB Ghana Ajaiyeoba, 2010;

Combretum apiculatum Sond.

related symptoms 2010)

Leaf tincture is used in the treatment of 2010)

Malvaceae Adansonia digitata L.

Cymbopogon citratus (DC.) Stapf. Leaf infusion is used in TB treatment

Used in Bhringarajasava, a liquid formulation (30 mL) Ayurveda (Samal,

Hook. f. & Thoms. et al., 2011)

Used in Bhringarajasava, a liquid formulation (30 mL) Ayurveda (Samal,

Used in Bhringarajasava, a liquid formulation (30 mL) 2016)

Ranunculus ternatus Thunb.

Simaroubaceae Brucea javanica (L.) Merr. Indonesia (Alvin et al.,

activity has been reported previously (Ahmad et al., 2016).

Table 3. Medicinal plants used against tuberculosis in Americas.

Plant family Botanical name Mode of preparation/administration Locations References

Lythraceae Punica granatum L.

In New Guinea, the bark is used to make a

Zingiberaceae Used in the treatment of TB-related symptoms Amazonia (Storey and

3. Targeting multidrug resistance in tuberculosis: management with phytochemicals and

3.1. Impact of MDR- and XDR-TB on public health

2011; Mishra et al., 2015; WHO, 2016).

As a consequence, there is an urgent need to develop novel anti-tuberculosis agents, particularly

3.3. Bisbenzylisoquinolone alkaloids

In a study by Sureram et al. (2012) bisbenzylisoquinoline alkaloids including tiliacorinine, 20-

3.4. Cinnamic acid derivatives

current anti-TB drugs (Lakshmananet al., 2011).

3.5. Fungal metabolites

fibroblast cells), with IC50 value of 6.97 µg/mL.

was reported for other cell lines.

3.7 Marine natural products

2016). The compound (–)-8,15-diisocyano-11(20)-amphilectene, a diterpene isolated from the Carribean

and Suh, 2016).

inhibition of peptidoglycan biosynthesis, though, noteworthy, teixobactin-resistant strains of M.

tuberculosis could not be generated (Ling et al., 2015).

3.9. Quinones and terpenes

MTb H37Ra, UA decreased mycolic acid biosynthesis in a dose-dependent manner as determined by

also identified as cucurbitacin E 2-O-β-D-glucopyranoside and cucurbitacin I 2-O-β-D-glucopyranoside

against the clinical isolates (Mehta et al., 2013).

In a publication by Uc-Cachón et al. (2014), naphthoquinones with anti-MTb activity were

and C2 (1,2-naphthoquinones) or positions C1 and C4 (1,4-naphthoquinones), and are found as

of biological activities, including antibacterial, antifungal, antiparasitic, antiviral, antiinflammatory and

Javad Sharifi-Rada,, Bahare Salehib, Zorica Z. Stojanović-Radićc, Patrick Valere Tsouh