PHYTOTHERAPY RESEARCH

Phytother. Res. 14, 303–322 (2000)

REVIEW ARTICLE
A Review of Antimycobacterial Natural
Products

Sandra M. Newton,1* Clara Lau1,2 and Colin W. Wright1

1
The School of Pharmacy, University of Bradford, West Yorkshire, UK
2
Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

Tuberculosis is a chronic infectious disease caused by several species of mycobacteria. Due to multi-
drug resistant strains of mycobacteria and to a high prevalence of tuberculosis in patients who have
acquired human immunodeficiency syndrome (AIDS), the number of patients infected with the disease is
increasing worldwide. Thus there is an urgent need for new effective antimycobacterial agents to replace
those currently in use. In this instance, the plant kingdom is undoubtedly a valuable source for new anti-
tuberculosis agents. The present review article reports the findings from an extensive literature search of
all plants that have been assessed for antimycobacterial/antitubercular activity over the past 20–30 years.
An attempt has been made to summarize the information in order to highlight those promising plant
species which are worthy of further investigation as leads for drug development. Over 350 plant
species from a wide range of families and origins, containing various chemical classes of compounds,
have been screened for such activity. A review of the relevant in vitro assays using different species
of pathogenic and non-pathogenic mycobacteria is also included. Copyright # 2000 John Wiley &
Sons, Ltd.
Keywords: mycobacteria; tuberculosis; plants; antimycobacterial; natural products; traditional medicine.

INTRODUCTION virus (HIV) infection (Zumla and Grange, 1998). With

The infectious killer disease, tuberculosis (TB), is the
leading cause of death worldwide from a single human
pathogen, claiming more adult lives than diseases such as
acquired immunodeficiency syndrome (AIDS), malaria,
diarrhoea, leprosy and all other tropical diseases
combined (Zumla and Grange, 1998). The organism
usually responsible is the tubercle bacillus, Mycobacter-
ium tuberculosis (MT), discovered by Robert Koch in
1882. However, M. bovis, which infects cattle may
also infect man and M. africanum is a cause of TB in
West Africa. Furthermore, a number of normally non-
pathogenic mycobacteria, especially M. avium, M.
intracellulare and M. scrofulaceum, cause opportunistic
infectious disease in patients with AIDS (Horne, 1996).
Pulmonary TB, the most common type of the disease, is
usually acquired by inhalation of the bacillus from an
infectious patient and causes irreversible lung destruc-
tion.
About one third of the world’s population is
currently infected with M. tuberculosis; 10% of those
infected will develop clinical disease, particularly
those who also have the human immunodeficiency
* Correspondence to: Dr S. M. Newton, The School of Pharmacy, University
of Bradford, West Yorkshire, BD7 1DP, UK.
the discovery of effective antimycobacterial agents
(including ethambutol, isoniazid, pyrazinamide, rifam-
picin and streptomycin) and a reduction in poverty,
there was a drastic decline in the number of TB cases,
especially in developed nations. However, since the
late 1980s, the number of cases of TB throughout the
world has been increasing rapidly due partly to the
emergence of multidrug resistant M. tuberculosis.
According to the World Health Organization (WHO,
1993), it was expected that the annual death rate caused
by TB will reach an overwhelming 3.5 million by the
year 2000.
Thus the TB problem requires urgent attention. Short
course anti-TB regimens initially using at least three first-
line drugs (including isoniazid, rifampicin and pyrazina-
mide) are effective. The major problems faced in
tuberculosis control are poor infrastructures for diagnosis
and drug supply and failure of patients to complete their
course of drugs. This is usually due to poor supervision
and medical care and, as a result, drug resistance
develops. Second-line drugs (e.g. capreomycin, kanamy-
cin, cycloserine, ethionamide) which are often more toxic
have to be used in this case. Furthermore, drugs with
broader ranges of activity are also required to target
emerging pathogens, such as those of the M. avium
complex. Hence, there is a great need to search for and
develop new, affordable, anti-TB agents.
For as long as man can remember, plants particularly,
have been used worldwide in traditional medicines for

Copyright # 2000 John Wiley & Sons, Ltd.

304 S. M. NEWTON ET AL.
the treatment of disease. It is estimated that even today
approximately two-thirds to three-quarters of the world’s
population rely on medicinal plants as their primary
source of medicines (McChesney, 1995). Today, many of
the drugs currently used are derived from natural
products or have depended upon a natural product for
their development and the recent discoveries of the
antimalarial artemisinin and the anticancer agent taxol
indicate the continuing importance of plant species in
drug discovery. However, only a small proportion of
plant species have been thoroughly investigated for their
medicinal properties (Frame et al., 1998) and undoubt-
edly there are many novel biologically active compounds
to be discovered. During the past two decades, pharma-
ceutical companies and research scientists have shown an
increased interest in phytomedicine. Currently large
numbers of species are being screened for pharmaco-
logical activities especially those used in traditional/folk
medicine. Although plant species have not so far yielded
antibacterial compounds of comparable potency to the
antibiotics produced by microorganisms, many plant
extracts have been tested for activity against microorgan-
isms in the anticipation that highly active compounds will
be found. With the urgent need for new anti-TB agents, it
is particularly appropriate at this time to review the
literature for information on plant species which have
been assessed for antimycobacterial activity. The present
review attempts to identify those species, which are
worthy of further investigation as leads for drug
development and to stimulate further work in this
important area.
IN VITRO TESTS FOR ANTIMYCOBACTERIAL
ACTIVITY
Screening plant extracts for antimycobacterial activity is
usually carried out using mycobacteria cultured in
various types of broth and agar based media. M.
tuberculosis has the disadvantages of being slow growing
so that tests take several weeks and containment facili-
ties are needed as it is a dangerous pathogen. Many
investigators have therefore used non-pathogenic
species of mycobacteria such as M. avium, M. intracel-
lulare and M. kansaii, which like M. tuberculosis are
slow growing, and other species including M. chelonei,
M. fortuitum and M. smegmatis which are faster growing
allowing tests to be completed in a few days. Most
commonly, the test methods employed are the disc
diffusion and the broth dilution methods. In the disc
diffusion method, paper discs impregnated with the
extract under test are placed on a semi-solid (agar
based) medium which has been inoculated with myco-
bacteria. After incubation, zones of inhibition of bacterial
growth around the discs are measured. The main
disadvantages with this method are that non-polar
compounds may not diffuse into the agar so that active
compounds may be missed and that it is not possible to
obtain reliable quantitative results for comparative
purposes. In the broth dilution method, the minimum
concentration required to inhibit bacterial growth (mini-
mum inhibitory concentration, MIC) is determined using
a series of tubes containing serial dilutions of the extract
in inoculated broth; however solubilization of the extracts
Copyright # 2000 John Wiley & Sons, Ltd.
under test may be a problem (Satim and Washington,
1991).
For high-throughput screening, rapid methods which
can be automated are needed; these have been reviewed
by Gordon et al. (1996). The first rapid methods
developed involved measuring the evolution of 14CO2
from M. tuberculosis cultured in medium containing
14
C-palmitic acid and formed the basis for the BACTEC
system (Becton-Dickinson, Oxford, UK). This is used
for the susceptibility testing of clinical isolates and can
provide results in an average of 5 days compared with
3–4 weeks for conventional methods. However, the
BACTEC system is not suitable for high-throughput
screening due to the technical difficulties involved in
measuring 14CO2. Chung et al. (1995) developed an
assay based on measuring the uptake of radiolabelled
uracil into M. aurum, a fast growing and non-pathogenic
species which appears to be a good model for M.
tuberculosis as it has a similar profile of sensitivity to
anti-TB drugs. The latter method may be used for high-
throughput screening and does not require containment
facilities but the separation of incorporated from unin-
corporated uracil is labour intensive. The major dis-
advantage of the above is the need for radiolabelled
substrates but this has been overcome with the develop-
ment of assays in which mycobacterial viability is
determined using either bacterial or firefly luciferase.
The bacterial enzyme uses reduced flavin (produced by
viable mycobacteria) to oxidize an added aldehyde
substrate (decanal) which is accompanied by the
production of light at 490 nm. Firefly luciferase is
dependent upon ATP generated by the mycobacteria to
decarboxylate luciferin, resulting in the production of
light at 562 nm. Light production may be measured
easily using a luminometer in high-throughput systems.
Several species of mycobacteria, including M. tubercu-
losis, have been genetically modified by inserting the
genes for the production of bacterial luciferase; only
viable bacilli emit light when decanal is added and there
is no requirement for growth so that susceptibility testing
may be carried out rapidly. Similarly, the gene for firefly
luciferase has been incorporated into a number of
mycobacteria species including M. aurum (Chung et
al., 1995).
Colorimetric methods are very suitable for use in
microtitre plates and the results may be easily obtained
using a spectrophotometer. Gomez-Flores et al. (1995)
reported an assay for testing against the M. avium
complex which depends on the ability of viable bacteria
to reduce dimethylthiazoldiphenyltetrazolium (MTT) to
formazan. Another similar method utilizes the redox dye
Alamar blue which changes colour from blue to pink in
the presence of viable M. tuberculosis (Yajko et al.,
1995). These assays have the advantages of being simple
and do not require radioactive substrates but require
several days for growth of the bacteria so that they may
not be as rapid as the bioluminescence methods described
above.
While simple antimycobacterial tests are convenient
for screening crude plant extracts and isolated com-
pounds, it must not be forgotten that M. tuberculosis is
primarily an intracellular pathogen residing in the acidic
vacuoles of macrophage cells. This environment may
affect the action of anti-TB drugs such as streptomycin
(activity reduced) and pyrazinamide (activity increased)
and it may be valuable to evaluate the ability of plant
Phytother. Res. 14, 303–322 (2000)
 Table 1. Medicinal plants/natural products which have been assessed for antimycobacterial activity
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/ extract(s) Activity Side effects/ toxicity Remarks Reference
Actaea spicata ± ± MT Ethanol extract Inhibitory dilution (no growth or ± High activity Grange and
(Ranunculaceae) less than 5 colonies) = 1:320 Davey, 1990
Adhatoda vasica India Leaf BCG Bromhexine Average MIC for 5 clinical ± Both compounds have in vitro inhibitory effects Grange and
(Acanthaceae) MT Ambroxol (semi-synthetic isolates of MT with ambroxol against MT Snell, 1996
derivatives of alkaloid was 64 mg/mL Preparations of the ¯owers, leaves and roots
vasicine) Average MIC for bromhexine have been widely used in India for the treatment
was 128 mg/mL for 3 clinical of tuberculosis, asthma and also as
isolates of MT expectorants (Dymock et al., 1893).
When agent dissolved in DMSO, Compounds are widely used as mucolytic
MIC of bromhexine was lowered agents.
Ambroxol has been shown to be well tolerated
clinically when given orally in up to 500 mg

Copyright # 2000 John Wiley & Sons, Ltd.

doses twice daily (Oosterhuis et al., 1993).
Ailanthus altissima ± ± MT (Quassinoids) Percentage inhibitions at 12.5 ± Activities of all quassinoids screened were very Rahman et
(Simaroubaceae) mg/mL are: low. <19% inhibition at 12.5 mg/mL. al., 1997
Shinjulactone-K 19% Rifampicin was used as the positive drug
Ailanthone 17% control
Shinjudilactone 15%
Allium sativum ± Bulb MT Diethyl ether extract Inhibitory effect at 0.5 mg/mL ± Inhibitory effect of the two higher Jain, 1998
(Liliaceae) Guinea-pigs and 1.0 mg/mL concentrations of garlic extractÐ0.5 and 1.0
mg/mL.
Guinea-pigs, which were inoculated with MT
and given garlic extract, produced fewer marked
lesions in the viscera.
Positive drug controls included, isoniazid, para-
aminsalicylic acid and streptomycin
± Bulb MT and 16 other Allicin (diallyl thiolsul®nate) Mean MIC (n = 6) is 1.67 mg/mL ± All 17 species of MT were inhibited by various Delaha and
species of isolated from water extract for MT concentrations of extract. Garagusi,
mycobacteria However, the mean MIC demonstrated very low 1985
activity
Garlic has been used in traditional Chinese and
Egyptian medicine for many centuries (Bolton et
al., 1982; Yuang, 1954)
Allium sativum ± Bulb Allicin (diallyl thiosul®nate) MIC (mean) ± Signi®cant activity. Abbruzzese
ANTIMYCOBACTERIAL NATURAL PRODUCTS

(Liliaceae) 1 MT 1 1.72 mg/mL Positive controls included isoniazid, et al., 1987

2 MAC 2 2.29 mg/mL streptomycin, ethambutol, rifampicin.
3 MK 3 1.96 mg/mL
± Leaf MT Aqueous extract MIC (complete inhibition) = ± Signi®cantly active Fitzpatrick,
1:640 dilution 1954
Alnus rubra Bong. Br C Bark MT Methanol extract Both parts of the plant ± Signi®cant activity. McCutcheon
(Betulaceae) Catkin MA completely inhibited growth of Isoniazid was used as positive control. et al., 1997
MT and MA at 50 mg extract/disc Previously used in traditional medicine by First
Nation's people
Aloe chinensis ± Leaf MT Ethanol extract Active. ± Activity against MT. Gottshall et
(Liliaceae) (Concentration not stated) Activity present when screened against SA al., 1949
and EC
Aloe succotrina ± Leaf MT Ethanol extract Active. ± Activity against MT. No activity when screened Gottshall et
(Liliaceae) (Concentration not stated) against SA and EC al., 1949
Alpinia Kumatake China ± MT Alcohol extract No inhibition of MT using a 1:50 ± No signi®cant activity Wang, 1950
Mak. dilution
(Zingiberaceae)

Phytother. Res. 14, 303–322 (2000)

305
 306

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Amyris elemifera L. Guad ± MT Taxalin (Oxazole) MIC (inhibited more than 99% of ± Texalin signi®cantly active Rastogi et
(Rutaceae) MA the bacterial population) al., 1998
MK (mg/mL)
Method 1 (BACTEC) = 25, 25, 25
Method 2 (agar dilution) = 25,
50, 50
For MT, MA, MK respectively
depending on the method used
Antirrhinum majus ± Calyx MT and other Ethanol extract MIC (MT) = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Scrophulariaceae) bacterial species 1951
Arnica montana ± ± MT Ethanol extract Inhibitory dilution (No growth Too toxic in high Used in homeopathic practice for relief of pain Grange and
(Asteraceae) or less than 5 colonies) = 1:160 doses to be and in¯ammation (Wren, 1988) Davey, 1990
clinically useful

Copyright # 2000 John Wiley & Sons, Ltd.

(Wren, 1988)
Azadirachta indica East Stem/ MT Methanol extract Concentration of 2 mg/mL ± No signi®cant activity towards the Fabry et al.,
A. Juss. Africa Bark/ MA allowed the growth of more mycobacterium and very low antibacterial 1998
(Meliaceae) (Kenya) Leaf MC than 10% of the inoculum of the activity.
MI 5 mycobacterial strains. Against Growth controls using Lowenstein-Jensen
and bacterial strains the fast growing bacteria MIC = medium were carried out
8 mg/mL
Azorella madreporica Chile Aerial MT Petroleum ether extract MIC (complete growth IC50 vs Vero cells Signi®cant activity/moderate toxicity Wachter et
Clos (Apiaceae) inhibition) of AC = 20 mg/mL was 184 mg/mL al., 1998
AC = Mulinane Diterpenoid Antitubercular activity also demonstrated in
extracts obtained from seven other Azorella
plants (A. compacta, A. monanthos,
A. patagonica, A. ®lamentosa, A. trifurcata,
A. crassipes, A. cryptantha)
Myroxylon ± ± MT Ethanol extract MIC (no growth or less than 5 ± High activity Grange and
balsamum var. colonies) = 1:640 dilution. Davey, 1990
pereirae
S. M. NEWTON ET AL.

(Leguminoseae)
Balsoamorhiza Br C Root MT Methanol extract Completely inhibited growth of ± Signi®cant activity McCutcheon
sagittata MA MT at 50 mg extract/disc No inhibition of MA with 50 mg extract/disc. et al., 1997
Pursh Nutt. Positive control - isoniazid
(Asteraceae)
Barbarea vulgaris ± Flower MT and other Ethanol extract MIC (MT) = 1:80 dilution ± Signi®cantly active Lucas et al.,
(Cruciferae) bacterial species 1951
Bidens pilosa L. Rwanda Leaf MT Ethanol extract Active against MT at 100 mg/mL ± Weak activity. Van Puyvelde
(Asteraceae) MAC No activity against MAC, MSi Used in Rwandese traditional medicine (Van et al., 1994
MSi and SLM at 1000 mg/mL Puyvelde et al., 1975, 1977, 1982)
SLM Controls using conventional antituberculosis
drugs
Borrichia frutescens USA Flower MT 1 (24R)- 24,25- MIC IC50 vs. Signi®cant activity of both compounds 1 and 2 Cantrell et al.,
L. (Sea Daisy) Leaf epoxycycloartane 1 8 mg/mL Vero cells = Highest level of anti-mycobacterial activity 1996
(Asteraceae) Stem 2 (3aH, 24R)-24,25- 2 8 mg/mL 1 71.8 mg/mL found in ¯ower extract
epoxycycloartane 3 128 mg/mL 2 39.8 mg/mL
3 (23R)-3-oxolanosta-8,24- 3 103.6 mg/mL
dien-23-ol
All isolated from
dichloromethane extract
Borrichia frutescens USA Flower MT Dichloromethane extract 100% inhibition against MT at ± Signi®cant activity Cantrell et al.,
L. (Asteraceae) MA 0.1 mg/mL. Positive controls include rifampicin, 1998a
99% inhibition against MA at clarithromycin
1 mg/mL.

Phytother. Res. 14, 303–322 (2000)

 Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Brucea ± ± MT Inhibition at 12.5 mg/mL ± Activities of quassinoids were very low. 0±19% Rahman et al.,
antidysenterica 1 Dehydrobruceantin 1 15% inhibition at 12.5 mg/mL 1997
(Simaroubaceae) 2 Bruceantin 2 9% Rifampicin was used as the positive control
3 Dehydrobruceantarin 3 8% drug
4 Bruceanol-F 4 3%
5 Dehydrobruceantinol 5 1%
(Quassinoids)
Brucea javanica ± ± MT Bruceoside-D 7% inhibition of MT at 12.5 ± Activities of quassinoids were very low. 0±19% Rahman et al.,
(Simaroubaceae) (Quassinoid) mg/mL inhibition at 12.5 mg/mL 1997
Rifampicin was used as the positive control
drug
Callistemon citrinus Puerto Leaf MSm Ethanol extract Inhibition zones for MSm LC50 = 168 mg (Brine Signi®cant activity. Positive (streptomycin) and Frame et al.,
(Myrtaceae) Rico MT ranged from 27 mm (1000 mg/ shrimp) negative (untreated) controls were included. 1998

Copyright # 2000 John Wiley & Sons, Ltd.

Mice mL) to 8 mm (25 mg/mL). No toxicity to mice Transitory inhibition of MT similar to growth
Artemia salina Leech MT sensitive at 100 mg/mL when given 500 mg/ inhibitory effects for known bacteriostatic
(Brine shrimp) 100 mL of plant agents
extract/ mouse i.p.
over 15 days
Canella winterana Guad Leaf MT Canellal (Sesquiterpene MIC (inhibited more than 99% of ± No signi®cant activity against MT, MA, MK Rastogi et al.,
(Canellaceae) MK dialdehyde) isolated from bacterial population) of AC was 1998
MA chloroform extract greater than 100 mg/mL for each
test organism
Guad Oil from MT Essential oil made up of MIC (inhibited more than 99% of ± No signi®cant activity Rastogi et al.,
leaf MK myrcene, b- farnesene linalol bacterial population) of essential 1998
MA and nerolidiol (all non-cyclic oil was greater than 100 mg/mL
terpenoids) for each test organism
Canscora decussata India ± MT Xanthone 1 (Mangiferin) MIC (concentration required for No obvious toxicity Signi®cant activity of total xanthones and MIC Ghosal and
Schult Albino rats Xanthone 2 growth inhibition) of total or side effects in was comparable to that of streptomycin Chaudhuri,
(Gentianaceae) Xanthone 3 xanthones = 10 mg/mL albino rats with Xanthone 1 showed only weak inhibitory 1975;
Xanthone 4 isolated from MIC of xanthone 1 alone = 200 total xanthones activity Ghosal et al.,
ethanol extract mg/mL (50 mg/kg i.p.) Used in traditional Indian medicine to treat 1978
tuberculosis (Chopra et al., 1956)
Centella asiatica India ± MT No reduction in the number of ± No signi®cant activity on the acid fastness and Herbert et al.,
Linn. (Umbelliferae) acid-fast bacilli with various viability of MT in vitro. 1994
concentrations of the active Asiaticoside (glycoside) has been isolated
ANTIMYCOBACTERIAL NATURAL PRODUCTS

extract previously from this plant and has been used to

treat leprosy patients from very early times
(Boiteau et al., 1949; Kakkar, 1988)
Cetraria islandica L. Iceland ± MAu Proto-lichesterinic acid MIC = 250 mg/mL ± Reputed to be effective in treatment of Ingolfsdottir
(Parmeliaceae) pulmonary tuberculosis (Vartia, 1973). et al., 1998
Controls included rifampicin, streptomycin,
isoniazid
Chaenactis douglasi Br C ± MT Methanol extract Complete inhibition of MT at ± Signi®cantly active McCutcheon
Hook. (Asteraceae) MA 50 mg extract/disc. et al., 1997
Small zone of clearing of MA at
50 mg extract/disc.
Chrysoma USA Root MT MIC (MT)= ± Signi®cantly active Lu et al., 1998
pauci¯osculosa MA 1 (4Z,8Z)-Matricaria ester 1 12.5 mg/mL Positive controls are rifampicin against MT and
Michx. (Asteraceae) 2 (2Z,8Z)-Matricaria ester 2 25 mg/mL clarithromycin against MA
3 (2Z,8-dehydro)-Matricaria 3 25 mg/mL
ester and other related MIC (MA)=
compounds 1 50 mg/mL
2 25 mg/mL
3 25 mg/mL

Phytother. Res. 14, 303–322 (2000)

307
 308

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Chrysanthum sinense China ± MT Alcoholic extract MIC = 1:50 dilution ± Signi®cant activity Wang, 1950
Sab.
(Asteraceae)
Chrysanthemum ± Leaf MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
segetum (Asteraceae) Calyx bacterial species 1951
Cinnamomum ± ± MT Ethanol extract MIC (no growth or less than 5 Likely to be too High activity Grange and
camphora colonies) = 1:1280 dilution toxic for clinical use Davey, 1990
(Lauraceae) (Wren, 1988).
Cinnamomum ± Leaf MT Water extract MIC (complete growth ± Signi®cantly active Fitzpatrick,
zeylanicum inhibition) = 1:640 dilution 1954

Copyright # 2000 John Wiley & Sons, Ltd.

(Lauraceae)
Cladonia arbuscula Iceland ± MAu Usnic acid (dibenzofuran MIC of active constituent was ± Activity but lower than the MIC for control Ingolfsdottir
Wallr. Rabenh. derivative) isolated from 32 mg/mL drugs, rifampicin (2 mg/mL), streptomycin et al., 1998
(Cladoniaceae) diethyl ether extract (0.25 mg/mL) and isoniazid (0.03 mg/mL)
Effective in the treatment of pulmonary
tuberculosis (Vartia, 1973)
Clematis integrifolia ± Leaf MT Water extract MIC (complete inhibition) = ± Signi®cant activity Fitzpatrick,
(Ranunculaceae) 1:640 dilution 1954
Clematis virginiana ± Leaf MT Water extract MIC (complete inhibition) = ± Signi®cant activity Fitzpatrick,
(Ranunculaceae) 1:640 dilution 1954
Coptis coinensia China Root MT Berberine bisulphate MIC = 1:800 dilution Berberine highly Signi®cant activity but highly toxic Wang, 1950
French (alkaloid) toxic by parenteral
(Ranunculaceae) injection (Chang,
1948)
Empetrum nigrum L. Br C Stem MT Methanol extract Complete inhibition of MT and ± Signi®cant activity. McCutcheon
(Empetraceae) MA MA at 50 mg extract/disc Positive control-isoniazid et al., 1997
Methanol extract Concentration of 2 mg/mL ± No signi®cant activity against the mycobacteria. Fabry et al.,
S. M. NEWTON ET AL.

Entada abyssinica A. East Stem MT

Rich (Leguminosae) Africa MA allowed the growth of more MIC 50% (mg/mL) ranged from 0.5±4 depending 1998
(Kenya) MC than 10% of the inoculum of the on bacteria
MI ®ve mycobacterial species
MTe
and 5 bacterial
species
Erigeron ± ± MT Matricaria lactones MIC (mg/mL), for both ± Signi®cant activity of one particular compound Lu et al., 1998
philadelphicus L. MA organisms, ranged from 12.5 ÿ (4Z, 8Z-matricaria ester) which gave a MIC of
(Asteraceae) >100 for each of the 12.5 mg/mL against MT
compounds tested
Erigeron strigosus USA Roots MT Dichloromethane extract 100% inhibition against MT and ± Signi®cant activity Cantrell et al.,
Muhl. (Asteraceae) MA MA at 0.1 mg/mL Positive controlsÐrifampicin, clarithromycin 1998a
Eriodictyon ± Leaf MT Ethanol extract Active (concentration not stated) ± Activity Gottshall et
glutinosum Also active against SA al., 1949
(Hydrophyllaceae)
Erythrina gibbosa Panama ± MT MIC (MT) ± ± Mitscher and
(Papilionaceae) MSm 1 Phaseollidin 1 8±25 mg/mL Baker, 1998a
2 Erythrabyssin II 2 8±25 mg/mL
3 Erygibiso-¯avone 3 >25 mg/mL
(All ¯avonoids) MIC (MSm)
2 0.78 mg/mL

Phytother. Res. 14, 303–322 (2000)

 Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Eucalyptus Brazil Leaf MDR MT Essential oil Only the slow growing ± Very weak activity Moreira et al.,
botryoides Smith MT mycobacteria were sensitive 1997; Leite et
(Myrtaceae) and 8 other species using 10mg/mL of essential oil al., 1998
Eucalyptus Brazil Leaf MDR MT Essential oil Only the slow growing ± Very weak activity Moreira et al.,
camadulensis Dehn MT and 8 other mycobacteria were sensitive 1997; Leite et
(Myrtaceae) species using 10 mg/mL of essential oil. al., 1998
MT, MA and MDR MT were
sensitive at 5 mg/mL of essential
oil
Eucalyptus citriodora Brazil Leaf MDR MT Essential oil Only slow growing were ± Very weak activity Moreira et al.,
Hook (Myrtaceae) MT and 8 other sensitive at 5mg/mL except MK 1997; Leite et
species of al., 1998
mycobacteria

Copyright # 2000 John Wiley & Sons, Ltd.

Eucalyptus deglupta Brazil Leaf MDR MT Essential oil MA and MSc were sensitive at ± Very weak activity against MA and MS. No Moreira et al.,
Smith (Myrtaceae) MT and 8 other 10 mg/mL of essential oil. All activity against all other species of mycobacteria 1997; Leite et
species of other fast and slow growing al., 1998
mycobacteria ones were resistant
Eucalyptus globulus Brazil Leaf MDR MT Essential oil Only MDR, MT, MT, MSc, MA ± Very weak activity Moreira et al.,
Labil (Myrtaceae) MT and 8 other were sensitive at 10 mg/mL 1997; Leite et
species of al., 1998
mycobacteria
± Leaf MT Ethanol extract Active (concentration not stated) ± Very weak activity Gottshall et
al., 1949
Eucalyptus grandis Brazil Leaf MDR MT Essential oil Only active against all slow ± Very weak activity Moreira et al.,
Smith (Myrtaceae) MT and 8 other growing mycobacteria, except 1997; Leite et
species of MA and MG, at 5 mg/mL al., 1998
mycobacteria
Eucalyptus maculata Brazil Leaf MDR MT Essential oil Only active against all the slow ± Very weak activity Moreira et al.,
Hook (Myrtaceae) MT and 8 other growing mycobacteria at 5 mg/ 1997; Leite et
species of mL, except MK al., 1998
mycobacteria
Eucalyptus Brazil Leaf MDR MT Essential oil Only active against all the slow ± Very weak activity Moreira et al.,
tereticornis Smith MT and 8 other growing bacteria at 5 mg/mL, 1997; Leite et
(Myrtaceae) species of except MK and MM al., 1998
mycobacteria
Euthamia USA Aerial MT Dichloromethane extract 100% inhibition of MT and MA ± Activity Cantrell et al.,
ANTIMYCOBACTERIAL NATURAL PRODUCTS

leptocephala Greene MA at 1 mg/mL 1998a

(Asteraceae)
Ferula communis Saudi Rhizome MI Ferulenol (Coumarino- MIC (mg/mL) of AC = 1.25 for ± Signi®cant activity. Al-Yahya et
(Umbelliferae) Arabia MX sesquiterpene) each of the mycobacterial Ferchromone was another compound identi®ed al., 1998
MC species which had an MIC of 50 mg/mL for each of the
MSm mycobacterial species and an MIC of 12.5 mg/mL
and other bacterial for each of the bacterial species
species Used in traditional medicine for skin infections,
fever and dysentery
Fragaria vesca Br C Leaf MT Methanol extract Small zone of clearing of MT at ± Positive controlÐisoniazid McCutcheon
L. var. bracteata MA 50 mg extract/disc. et al., 1997
Heller No activity against MA at 50 mg
Davis extract/disc
(Rosaceae)
Galipea of®cinalis ± ± MT Ethanol extract MIC (no growth or less than 5 ± High activity Grange and
(Angustura vera) colonies) = 1:320 dilution Used to treat diarrhoea and fevers Davey, 1990
(Rutaceae) Preparation listed in the British
pharmaceutical codex, 1934.

Phytother. Res. 14, 303–322 (2000)

309
 310

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Galipea of®cinalis ± Bark MT Ethanol extract (Alkaloids) MIC (mg/mL) ± Active, however, none of the compounds Houghton et
(also known as 1 Cusparine Ranged from 6.25±629 showed activity as great as the two positive al., 1999
Cusparia febrifuga 2 Galipine depending on the fraction and controls usedÐisoniazid and rifampicin
Humb) (Rutaceae) 3 4-methoxy-2-n- the strain of MT Traditionally used as a bitter tonic and febrifuge
(Angostura bark) pentylquinoleine Similar alkaloids from other Galipea species
4 N-Methyl-2-quinolone have shown activity against Leishmania,
Trypanosoma, Plasmodium species (Spath and
Pikl, 1930; Fournet et al., 1993, 1994, 1996) and
snails (Vieira and Kubo, 1990)
Geum macrophyllum Br C ± MT Methanol extract Complete inhibition of MT at ± Signi®cant activity McCutcheon
Willd.var. MA 50 mg extract/disc. Positive controlÐisoniazid et al., 1997

Copyright # 2000 John Wiley & Sons, Ltd.

macrophyllum No inhibition of MA at 50 mg
(Rosaceae) extract/disc
Glehnia littoris Br C Root MT Methanol extract Complete inhibition of MT and ± Signi®cant activity McCutcheon
F. Schmidt ssp MA MA at 50 mg extract/disc Positive control±isoniazid et al., 1997
Leiocarpa (Mathias)
Hult. (Umbellifereae)
Glycyrrhiza glabra L. China ± MT Licoiso-¯avone (Flavonoid) Less active against MSm (50 mg/ ± ± Mitscher and
(Leguminoseae) MSm mL) than MT (25 mg/mL) Baker, 1998a,b
Guaiacum of®cinale ± ± MT Ethanol extract MIC (no growth or less than 5 Likely to be toxic for High activity Grange and
(Zygophyllaceae) colonies) = 1:160 dilution clinical use Davey, 1990
Harrisonia abyssinica East Root MT Methanol extract No signi®cant activity against ± Against the fast growing bacteria, the extract Fabry et al.,
Oliv. Africa MA the mycobacteria showed MICs and MBCs of 8 mg/mL 1998
(Simaroubaceae) (Kenya) MC
MTe
MI and 6
bacterial species
Heracleum maximum Br C Root MT Methanol extract Complete inhibition of MT and ± Signi®cant activity. McCutcheon
S. M. NEWTON ET AL.

Bartr. (Umbelliferae) MA MA at 50 mg and 10 mg extract/ Positive controlÐisoniazid et al., 1997

disc
Humulus lupulus ± Flower MT Ethanol extract Active (concentration not stated) ± Signi®cant activity Gottshall et
(Cannabinaceae) Activity also towards SA and EC al., 1949
Hydrastis canadensis Eastern Root MSm Ethanol extract MIC of AC ± Active. Gentry et al.,
(Golden Seal) North MAC Berberine (alkaloid) MSm = 25 mg/mL Berberine has been demonstrated to reduce the 1998
(Ranunculaceae) America BCG and various BCG = 200 mg/mL infectivity of bacteria, fungi and protozoa in
bacterial species MAC = 50 mg/mL animals and humans by inhibiting the adherence
of microorganisms to the host cells (Amin et al.,
1969; Preininger, 1975; Subbaiah and Amin,
1967; Sun et al., 1988)
North ± MSm Berberine (alkaloid) More active in vitro against ± The anti-TB effect was probably due to the large Mitscher and
America MT MSm (25 mg/mL) than against amount of berberine contained in the plant Baker, 1998a,b
MA MT
Hypericum calycinum ± Leaf MT Ethanol extract Active. (concentration not stated) ± Signi®cant activity Gottshall et
(Hypericaceae) al., 1949
Hypericum Br C ± MT Methanol extract Small zone of clearing of MT at ± Signi®cant activity at 10 mg extract/disc McCutcheon
perforatum L. MA 50 mg extract/disc. towards MA et al., 1997
(Hypericaceae) Greatly inhibited growth of MA Positive controlÐisoniazid
at 10 mg extract/disc
Inula helenium L. USA Root MT Dichloromethane and hexane 100% inhibition against MT at ± Signi®cant activity Cantrell et al.,
(Asteraceae) extracts 0.1 mg/mL Positive controlsÐrifampicin, clarithromycin 1998a

Phytother. Res. 14, 303–322 (2000)

 Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
± Root MT 1 alantolactone 100 mg/mL crude hexane and ± Signi®cant activity Cantrell et al.,
2 iosalantolactone chloroform extracts exhibited Rifampicin was used as the positive control 1996b
3 11,13-dihydroisoalantolac- 100% inhibition of MT. Used in traditional medicine for treatment of
tone (Eudesmanolides) 100 mg/mL methanol extract lung disorders and against TB (Moerman, 1986)
isolated from hexane, exhibited 83% inhibition Eudesmanolides are also found in Montanoa
dichloromethane and MIC of AC (mg/mL) = speciosa and Rudbeckia subtomentosa
methanol extracts. 1 32
2 32
3 >128
Ipomoea purga ± ± MT Ethanol extract MIC (no growth or less than 5 Has purgative Signi®cantly active, but may be unsuitable due Grange and
(Jalapa) colonies) = 1:160. properties to purgative property Davey, 1990

Copyright # 2000 John Wiley & Sons, Ltd.

(Convolvulaceae) Partial inhibition = 1:320 dilution

Juniperus communis Br C ± MT Methanol extract Greatly inhibited growth of MT ± Signi®cant activity. McCutcheon
L. (Cupressaceae) MA at 50 mg extract/disc. Positive control-isoniazid et al., 1997
Small zone of clearing of MA at
50 mg extract/disc
Juniperus excelsa Saudia Leaf MSm Ethanol extract followed by MIC(mg/mL)= ± Signi®cant activity, particularly of compound 1, Muhammad et
M.Bieb. Arabia MI partition between n-hexane 1 5 mg/mL against each species against all the mycobacterium species and al., 1992
(Cupressaceae) MX and acetonitrile 2 32 mg/mL (only tested on compound 2 against MSm.
MC Ethanol extraction yielded MSm) Controls included streptomycin and isoniazid
the compounds, 3 Inactive (only tested on MSm) (MIC = 10 mg/mL)
1 Ferruginol 4 Not tested
2 Sandaracopimeric acid
3 Hinokinol
4 3b-hydroxy-sandaracopi-
meric acid
Juniperus procera Saudi Bark MI Ethanol extract, which was MIC of compound 1 = 1.25mg/mL ± Signi®cantly active but less potent than the Muhammad et
Hochst Arabia MX further partitioned between for each species of mycobacteria positive control, amikacin sulphate (MIC = 0.25 al., 1996
(Cupressaceae) MC chloroform and aqueous More potent than its abietane mg/mL against each species.) However, MIC
MSm and bacteria MeCN. derivatives. (MIC = 5.0 mg/mL and values for streptomycin and isoniazid were
genera Chloroform fraction yielded 2.5 mg/mL for (‡)-ferruginol and higher at 10 mg/mL.
diterpenes, 1 7b-Hydro- (‡)-totarol respectively) Compounds 2 and 3 were not tested against the
xyabieta-8,13-dien-11,12- Also active against the genera of mycobacteria but compound 2 was weakly active
ANTIMYCOBACTERIAL NATURAL PRODUCTS

dione bacteria against the bacteria species and compound 3

Other abietane derivatives of was inactive
compound 1 which were
tested included (‡)-ferruginol
and (‡)-totarol
2 Cryptotrienolic acid
3 Isocupressic acid
Karwinskia USA Root MSm and 6 other Dichloromethane and Karwinaphthol A inhibited ± Signi®cant activity. Mitscher et al.,
humboldtiana types of bacteria ethanol extract. growth of MSm at 12.5 mg/mL Seeds are poisonous but fruit pulp is edible. 1985
(Rhamnaceae) Karwinaphthol A and Karwinaphthol B at 50 Used locally in Mexico to treat convulsions
Karwinaphthol B mg/mL (Usher, 1974)
Lavandula France Flower MC Essential lavandino oils Diameter of the zones of ± Signi®cant antimycobacterial activity on all the Gabbrielli et
angustifolia Mill. MF inhibition (in mm) ranged from species al., 1988
(lavender) (Labiatae) MK 20±35 depending on the year the Extracts also were comparable to the standards
MM samples were harvested and the Standards included Amikacin and Kanamycin
MSc species tested against.

Phytother. Res. 14, 303–322 (2000)

311
 312

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Leucas volkensii Kenya Aerial MT Methanol extract MIC ± Signi®cant activity from all the compounds. (E)- Rajab et al.,
Gurke (Labiatae) 1 (E)-phytol 1 2 mg/mL phytol, phytanol, (Z)-phytol and the mixture of 1998
2 Phytanol 2 2 mg/mL (E)- and (Z)-phytol were the most active and their
3 (Z)- phytol 3 2 mg/mL activities were in same range as ethambutol
4 Mixture of E)-and (Z)-phytol 4 2 mg/mL (0.95±3.8 mg/mL)
5 Geraniol 5 64 mg/mL
6 Farnesol 6 8 mg/mL
Lomatium dissectum Br C Root MT Methanol extract Complete inhibition of MT and ± Signi®cant activity. McCutcheon
Nutt (Umbelliferae) MA MA at 50 mg extract/disc Positive control±isoniazid et al., 1997
Lonicera japonica Th. China ± MT ± MIC (complete inhibition) = 1:50 ± Signi®cant activity Wang, 1950
(Caprifoliaceae) dilution
Lupinus hirsutus ± Root MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Leguminosae) bacterial species 1951

Copyright # 2000 John Wiley & Sons, Ltd.

Lupinus polyphyllus ± Leaf MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Leguminosae) Stem bacterial species 1951
Root
Magnolia acuminata USA Bark MT Dichloromethane extract 100% inhibition against MT and ± Signi®cantly active. Cantrell et al.,
(Magnoliaceae) MA MA at 0.1 mg/mL Positive controlsÐrifampin, clarithromycin 1998a
Magnolia grandi¯ora ± ± MT MIC (mg/mL) vs MT and MA ± Signi®cant activity Fischer et al.,
and Magnolia MA respectively are Parthenolide was the most active 1998
virginiana 1 Costunolide 1 32, 128 germacranolide against both MT and MA
(Magnoliaceae) 2 Parthenolide 2 16, 64 Other a-methylene-g-lactone-bearing
3 1(10)-epoxycostunolide 3 64, 128 sesquiterpene lactones are moderately active
(Germacranolides) against MT with MICs of 64 mg/mL and below
Positive controls include rifampicin and
clarithromycin
Magnolia grandi¯ora USA Flower MT Dichloromethane extract 100% inhibition of MT at ± Weak activity Cantrell et al.,
L. (Magnoliaceae) Fruit MA 1000 mg/mL. 1998a
Leaf 84%±92% inhibition of MA
S. M. NEWTON ET AL.

depending on part of plant used

Mammea americana Puerto Leaf MSm Ethanol extract 10 mm inhibition zone at 25 mg/ LC50 = 224.6 mg/mL Signi®cantly active Frame et al.,
(Guttiferaceae) Rico MT disc for MSm. (Brine shrimp). Bactericidal inhibitory pattern on MT growth 1998
Mice Activity towards MT at 50 mg No toxicity to mice comparable to that of streptomycin (used as
Artemia salina at 500 mg/100 mL of a positive control)
Leach (Brine shrimp) plant extract mouse
given i.p. over 15
days
Mangifera indica Puerto Leaf MSm Ethanol extract 12 mm inhibiton zone at 1000 mg/ LC50=1000 mg/mL Active. Low degree of toxicity at 500 mg/100 mL of Frame et al.,
(Anacardiaceae) Rico Mice disc for MSm. (Brine shrimp) plant extract/mouse given i.p. over for 15 days 1998
Artemia salina Active towards MT at 250 mg Streptomycin used as positive control
Leach (Brine shrimp) Bacteriostatic activity towards MT at 250 mg/mL
Marchantia Puerto Leaf MSm Ethanol extract 7 mm inhibition zone at 50 mg/ LC50 = 1000 mg/mL Signi®cantly active. Frame et al.,
polymorpha Rico MT disc for MSm. (Brine shrimp) Low toxicity. Transitory inhibition of MT growth 1998
(Marchantiaceae) Mice Active towards MT at 100 mg No toxicity in mice similar to the growth inhibitory effects for known
Artemia salina at 500 mg/100 mL of bacteriostatic effects.
Leach (Brine shrimp) plant extract mouse Streptomycin used as negative control
given i.p. over 15
days
Melia volkensii Kenya Seeds MT Methanol extract MIC(mg/mL) However it is Signi®cantly active. Cantrell et al.,
Gurke 112b hydroxykulactone 1 16 poisonous at higher Used in folk medicine to alleviate pain - tea 1999a
(Meliaceae) 2 6b hydroxykulactone 2 4 dose levels prepared from bark.
3 Kulonate 3 16 (Kokwaro, 1976) Kulonate previously isolated from Melia
azedarach (Chiang and Chang, 1973; Ochi et al.,
1977)

Phytother. Res. 14, 303–322 (2000)

 Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Momordica charantia Puerto Leaf MSm Ethanol extract 30 mm inhibition zone at 500 mg/ LC50 = 33 mg/mL Signi®cantly active Frame et al.,
L. (Cucurbitaceae) Rico MT disc for MSm. Active against MT (shrimp). No 1998
Mice at 500 mg toxicity in mice at
Artemia salina 500 mg/100 mL of
Leach (Brine shrimp) plant extract/mouse
given i.p. over 15
days
Moneses uni¯ora L. Br C Aerial MT Methanol extract Complete inhibition of MT and ± Signi®cant activity. Positive control-isoniazid McCutcheon
(Ericaceae) MA MA at 50 mg and 10 mg extract/ et al., 1997
disc

Copyright # 2000 John Wiley & Sons, Ltd.

Myrica aspleni¯ora ± Leaf MT Ethanol extract, Boiling water Active against MT with both ± Signi®cant activity Gottshall et
(Myricaceae) EC extract extracts (concentration not al., 1949
SA stated).
No activity against EC and SA
Nuphar lutea L. Br C Rhizome MT Methanol extract Complete inhibition of MT at ± Signi®cant activity at 50 mg/mL McCutcheon
(Nymphaceae) MA 50 mg extract/disc. Small zone of Positive control-isoniazid et al., 1997
clearing of MA with 50 mg
extract/disc
Ocimum sanctum ± Leaf MT Aqueous Complete inhibition of all strains ± Signi®cant activity. Controls included Reddi et al.,
Linn. Mant (two with a 1:1 dilution of the extract streptomycin, isoniazid and ethambutol 1986
(Unknown) resistant strains)
Oplopanax horridus Br C Inner MT Methanol extract Complete inhibition of MT and ± Signi®cant activity McCutcheon
Smith Miq. bark MA MA with 10 mg extract/disc Positive control-isoniazid et al., 1997
(Araliaceae)
Oplopanax horridus North Inner MT 1 Falcarindol All active constituents methanol ± All compounds signi®cantly active against MT Kobaisy et al.,
(Devil's club) America bark Isoniazid 2 Falcarinol and chloroform extracts were Used by ®rst nations people in traditional 1997
(Araliaceae) resistant-MA 3 Oplopandiol active at a concentration of medicine for a variety of ailments such as
Other bacterial and 4 Active oil 1 (C20H28O4) 10 mg/disc against MT and diabetes, rheumatism, tuberculosis, colds,
fungal species 5 Active oil 2 (C20H30O4) isoniazid resistant MA headaches and lung ailments (Turner, 1982;
All polyynes isolated from Falcarinol and active oil 2 Turner et al., 1990)
extraction with methanol (C20H30O4) completely inhibited
followed by dichloromethane growth of MT and isoniazid
ANTIMYCOBACTERIAL NATURAL PRODUCTS

resistant MA at 20 mg/disc
Panax ginseng ± Root MT Methanol extract, ethanol Mycobacterial growth inhibited ± Ginseng is used in traditional medicine Chang et al.,
(Araliaceae) extract, ether extract by 100 mg/mL ether extract and 1979
by 500 mg/mL of ethanol and
methanol extracts
Parmelia saxatilis L. ± ± MAu Salazinic acid MIC = 250 mg/mL ± Weak activity Ingolfsdottir et
(Parmeliaceae) Controls included rifampicin, streptomycin, al., 1998
isoniazid
Pentas longi¯ora Rwanda Root MT Ethanol extract Showed activity against MT and ± Weak activity. Van Puyvelde
Oliv. (Rubiaceae) MAC MSi at 1000 mg/mL Used in Rwandese traditional medicine for the et al., 1994
MSi No activity against all other treatment of pulmonary diseases (Van Puyvelde
SLM species et al., 1975, 1977, 1982)
Controls using conventional anti-tuberculosis
drugs
Petasites japonicas ± Root MT Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Compositae) 1951

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313
 314

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Picrasma ailanthoides ± ± MT Inhibitions at 12.5 mg/mL are ± Activities of quassinoids were very low ranging Rahman et al.,
(Simaroubaceae) 1 Nigakihemiacetal 1 12% from 1±19% inhibition at 12.5 mg/mL 1997
2 Nigakilactone-L 2 9% Positive control-rifampicin
3 Neoquassin 3 8%
4 Nigakihemiacetal-A 4 8%
5 Quassin 5 7%
6 Nigakilactone-H 6 5%
7 Nigakilactone-E 7 5%
8 Picrasin-A (Quassinoids) 8 4%
Pieris ¯oribunda ± Leaf MT Water extract MIC (complete inhibition) = 1:640 ± Signi®cant activity Fitzpatrick,

Copyright # 2000 John Wiley & Sons, Ltd.

(Ericaceae) dilution 1954
Pieris japonica ± Leaf MT Water extract MIC (complete inhibition) = 1:640 ± Signi®cant activity Fitzpatrick,
(Ericaceae) dilution 1954
Pilocarpus racemosus Guad ± MT Pilocarpine (alkaloid) MIC (mg/mL) was greater than ± No signi®cant activity against MT, MA, MK Rastogi et al.,
(Rutaceae) MK 100 for each test organism 1998
MA
Pinus contorta Br C ± MT Methanol extract Complete inhibition of MT with ± Signi®cant activity at 50 mg extract/disc for MT McCutcheon
(Pinaceae) MA 50 mg extract/disc. et al., 1997
Small zone of clearing of MA
with 50 mg extract/disc
Piper cubeba Indo- ± MT Ethanol extract MIC (no growth or less than 5 ± High speci®c activity. Used to treat pulmonary Grange and
(Piperaceae) nesia colonies) = 1:320 dilution and urinary infections and is antibacterial in vitro Davey, 1990
(Wren, 1988)
Polystitchum Br C ± MT Methanol extract Small zone of clearing of MT and ± Positive control-isoniazid McCutcheon
munitum Kaulf MA MA with 50 mg extract/disc et al., 1997
(Polypodiaceae)
Populus tremuloides Br C ± MT Methanol extract Complete inhibition of MT with ± Signi®cant activity of 50 mg extract/disc against McCutcheon
S. M. NEWTON ET AL.

(Salicaceae) MA 50 mg extract/disc. MT. et al., 1997

Small zone of clearing of MA Positive control-isoniazid
with 50 mg extract/disc
± ± MT Ethanol extract MIC (no growth or less than 5 Appears to be non- High activity Grange and
colonies) = 1:320 dilution. Partial toxic. Has been Davey, 1990
inhibition of MT at 1:640 given by inhalation
to treat pulmonary
infections (Nikulin et
al., 1979)
Propolis Chile Resin MT Methanol extract partitioned MIC (mg/mL) of crude extract = ± Signi®cant activity of all compounds against MT Valcic et al.,
MA between dichloromethane 128 mg/mL for both species and compound 1 against MA 1999
and water MIC (mg/mL) of compounds = Controls included rifampicin and clarithromycin
Organic phase yielded 17 1 64 mg/mL (MT and MA)
compounds. Active ones 2 64 mg/mL (MT) and 128 mg/mL
included, (MA)
1 Viscidone-14-acetate 3 64 mg/mL (MT) and 128 mg/mL
2 Coniferyl aldehyde (MA)
3 Dihydrobenzofuran ligan
aldehyde
Primula malacoides ± Flower MT Ethanol extract MIC = 1:80 dilution ± Signi®cantly active Lucas et al.,
(Primulaceae) Peduncle 1951

Phytother. Res. 14, 303–322 (2000)

 Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Prunus mume USA Berry MT Citric acid Citric acid extract inhibited ± Citric acid was shown to have speci®c and Roper and
(Rosaceae) Hong Malic acid growth of MT on agar, giving a signi®cant activity against MT Ma., 1968; Ma
Kong and various other acids 7.1 mm mean radial width of Used in traditional Chinese medicine (Li Shih- and Roper,
inhibition. This was highest of all Chen, 1930; Kariyone and Kimura, 1962) 1968
acids tested
Bioactivity is rather low when
compared with drugs such as
INH
Punica granatum L. China ± MT Alcohol extract MIC (complete inhibition) = 1:50 ± Signi®cant activity Wang, 1950
(Punicaceae) dilution
Pyrus atrosanguinea ± Leaf MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Rosaceae) bacterial species 1951
Rauwol®a Guad ± MT Lochnerin (Indole alkaloid) MIC was 100 mg/mL for each test ± No signi®cant activity against MT, MA, MK Rastogi et al.,

Copyright # 2000 John Wiley & Sons, Ltd.

biauriculata MA organism 1998
(Apocynaceae) MK
Rheum of®cinale ± Root MT Ethanol extract Active (concentration not stated) ± Signi®cant activity Gottshall et
(Polygonaceae) al., 1949
Rhamnus cathartica ± ± MT Ethanol extract MIC (no growth or less than 5 Has a purgative High speci®c activity but purgative property Grange and
(Rhamnaceae) colonies) = 1:160 dilution property Davey, 1990
Rosa canina ± Leaf MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Rosaceae) Stem bacterial species 1951
Flower
Rosa nutkana Presl Br C ± MT Methanol extract Small zone of clearing of MT and ± Positive control±isoniazid McCutcheon
var. nutkana MA MA with 50 mg extract/disc et al., 1997
(Rosaceae)
Rudbeckia ± Root MT 1 Allolantolactone 3 100 mg/mL dichloromethane ± Signi®cant activity Cantrell et al.,
submentosa Leaf 2 oxoalloalantolactone extract of root gave a 99% Rifampicin was used as the positive control 1999b
(Asteraceae) Stem isolated from inhibition. Compounds previously isolated from
Flower dichloromethane extract MIC (mg/mL) = Eupatorium quadrangularae (Okunade and
1 32 Wiemer, 1985)
2 128
Salix caprea ± Flower MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Salicaceae) bacterial species 1951
Salvia Hypargeia Eastern Root MT and bacterial Hypargenin F isolated from Activity against MT at 250 mg/mL ± Active against MT Ulubelen et
Fisch. Et Mey. Turkey strains acetone extract Active also against various genera of bacteria al., 1988
ANTIMYCOBACTERIAL NATURAL PRODUCTS

(Labiatae) with MIC values (mg/mL) ranging from 62.5±125

Salvia multicaulis Turkey Root MT MIC ± All signi®cantly active but Norabietanes 2, 4, 5, Ulubelen et
Vahl. (Labiatae) 1 Norabietane 1 1 5.6 mg/mL and Abietane 2 are most potent al., 1997
2 Norabietane 2 2 0.46 mg/mL Test compounds 1±7 gave comparable values to
3 Norabietane 3 3 2.0 mg/mL standard anti-tubercular agents i.e. rifampicin
4 Norabietane 4 4 1.2 mg/mL Salvia species used in traditional medicine and
5 Abietane 1 5 1.2 mg/mL have been associated with antibacterial,
6 Abietane 2 6 0.89 mg/mL antituberculous, and antiphlogistic activities (Lin
7 Primarane 7 7.3 mg/mL et al., 1989)
All isolated from an acetone
soluble extract
Salvia of®cinalis ± Leaf MT Ethanol extract Active ± Signi®cant activity. Gottshall et
(Labiatae) Also active against SA al., 1949
Sanguinaria ± Root MT Ethanol extract Active ± Signi®cant activity. Gottshall et
canadensis Also active against SA al., 1949
(Papaveraceae)
Sanguisorba China ± MT Alcohol extract MIC (complete inhibition) = 1:50 ± Signi®cant activity Wang, 1950
of®cinalis L. dilution
(Rosaceae)

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315
 316

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Santolina ± Root MT and other Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
chamaecyparissus bacterial species 1951
(Asteraceae)
Saussurea lappa ± ± MT Dehydrocostus lactone MIC (mg/mL = ± Signi®cant activity Cantrell et al.,
(Asteraceae) MA 2 (MT) 1998b
16 (MA)
Schizandra chinensis China Berry MT Citric acid, Malic acid and Citric acid inhibited growth of ± Citric acid was shown to have low activity Roper and Ma,
(Schisandraceae) various other acids MT on agar giving a mean radial against MT 1968

Copyright # 2000 John Wiley & Sons, Ltd.

width of 7.1 mm. However the hydrazides (from other acids) Ma and Roper,
This was the highest of all acids produce even greater activity than the parent 1968
tested. acids
Bio-activity is rather low when Used in traditional Chinese medicine (Li Shih-
compared with drugs such as Chen, 1930; Kariyone and Kimura, 1962)
INH
Solanum Libya Berry MI Solsodomine A Solsodomine A MIC = 10 mg/mL No cytotoxic activity Signi®cant activity of Solsodomine A towards El Sayed et
sodomaeum L. Solsodomine B Solsodomine B had no activity towards Vero cells MI. al., 1998
(Solanaceae) (Pyrrole alkaloids) on MI (dose not stated) Solsodomines A and B did not show in vitro
antimalarial, antifungal or cytotoxic activity
(concentrations not stated).
Solidago canadensis ± ± MT C-10-O-acylated matricaria MIC values (mg/mL) for MT and ± Signi®cant activity Lu et al., 1998
L. (Asteraceae) MA esters and a dehydro- MA ranged from 12.5 to >100
matricaria ester mg/ml
Solidago rugosa North Root MT (Diterpenes) MIC > 100 mg/mL against MT and ± All show no signi®cant anti-mycobacterial Lu et al., 1995
Mill. (Asteraceae) America Aerial MA 1 Kolavenol MA for all 6 compounds tested activity
S. M. NEWTON ET AL.

2 Hardwickiic acid Compound 2 also present in Hardwickia pinnata

3 Hydroxymanool Compound 4 also present in Juniperus
4 Monoacetate pseudosabina
5 Diacetate
6 Entabietic acid isolated
from the dichloromethane
extract
Solidago arguta USA Root MT Dichloromethane extract 100% inhibition against MT at ± Signi®cantly active Cantrell et al.,
Ait. (Asteraceae) MA 0.1 mg/mL. 80% inhibition Positive controls include rifampicin and 1998a
against MA at 0.1 mg/mL clarithromycin
Spilanthes East Root MT Methanol extract Concentration of 2 mg/mL ± No signi®cant activity against the mycobacteria Fabry et al.,
mauritiana Africa Flower MA allowed the growth of more than 1998
A. Rich. DC. (Kenya) MC 10% of the inoculum of the 5
(Asteraceae) MTe mycobacterial strains
MI
and bacterial strains
Stereocaulon Iceland ± MAu MIC = ± Controls included rifampicin, streptomycin, Ingolfsdottir et
alpinum 1 Atranorin 1 250 mg/mL isoniazid al., 1998
(Stereocaulonaceae) 2 Lobaric acid 2 125 mg/mL

Phytother. Res. 14, 303–322 (2000)

 Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Strobilanthus cusia China/ ± 1 MT Tryptanthrin (indole- MIC ± Potency of compound in same range as that of Mitscher and
(Acanthaceae) Taiwan 2 MSm quinazolinone alkaloid) 1 1 mg/mL antitubercular drugs already in use, i.e. Baker, 1998a
3 MAC 2 4 mg/mL streptomycin and ethambutol
3 2 mg/mL Positive controls included various standard
(1 and 3 using BACTEC method antitubercular drugs
and 2 using agar dilution Active against MDR MT
method) Chinese/Taiwanese medicinal plant. Has folkloric
reputation for the topical treatment of athletes
foot
China/ ± 1 MT Tryptanthrin (indole- More potent against MT (1 mg/ ± High signi®cant activity. Mitscher and

Copyright # 2000 John Wiley & Sons, Ltd.

Taiwan 2 MA quinazolinone alkaloid) mL) and MA (4 mg/mL) than Also active against drug sensitive and drug Baker, 1998b
3 MSm against MSm (6 mg/mL) resistant MT and MAC.
Compound also isolated from Polygonum
tinctorium and Isatis tinctoria
Syringa vulgaris ± Leaf MT Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Oleaceae) Flower 1951
Syzgium jambos Puerto Leaf MSm Ethanol extract 30 mm inhibition zone at 500 mg/ LC50 = 93mg/ml Signi®cant activity Frame et al.,
(Myrtaceae) Rico MT disc for MSm. (brine shrimp). No 1998
Mice Active against MT at 500 mg toxicity to mice at
Artemia salina 500mg/100ml of
Leach (Brine shrimp) plant extract/mouse
given i.p. over 15
days.
Tabernaemontana Guad ± MT MIC (mg/mL) ± Signi®cant activity by both compounds Rastogi et al.,
citrifolla MA 1 Ibogaine 1 50, 100, 50, 1998
(Apocynaceae) MK 2 Voacangine 2 50, 50, 100
(Indole alkaloids) for MT, MA, MK respectively
Taxus canadensis ± Leaf MT Ethanol extract MIC = 1:80 dilution ± Signi®cant activity Lucas et al.,
(Taxaceae) 1951
Tetradenia riparia Rwanda Leaf MT Diterpenediol in ethanol Signi®cant activity of AC against ± Used in Rwandese traditional medicine in the Van Puyvelde
Hochst. Codd. MAC extract MT, ranging between 25±100 mg/ treatment of pulmonary diseases (Van Puyvelde et al., 1994
(Lamiaceae) MSi mL, depending on the strain et al., 1975, 1977, 1982)
ANTIMYCOBACTERIAL NATURAL PRODUCTS

SLM No activity from AE against MAC Controls using conventional antituberculosis

and SLM at 1000 mg/mL. drugs
Terminalia spinosa East Stem MT Methanol extract Concentration of 2 mg/mL ± No signi®cant activity against mycobacteria Fabry et al.,
Engl. (Combretaceae) Africa MA allowed the growth of more than 1998
(Kenya) MC 10% of the inoculum of the 5
MTe mycobacterial strains
MI and bacterial
strains
Teucrium ± Whole MT Ethanol extract MIC = 1:80 dilution ± Signi®cantly active Lucas et al.,
chamaedrys plant 1951
(Labiateae)
Triphasia trifolia Guad Leaf MT Isomeranzin MIC was 100 mg/mL for each ± No signi®cant activity Rastogi et al.,
(Rutaceae) MA Heraclenol test organism and active 1998
MK (Coumarins) isolated from constituent
chloroform extract

Phytother. Res. 14, 303–322 (2000)

317
 318

Copyright # 2000 John Wiley & Sons, Ltd.

Table 1. Continued.
Model used/ Route
Plant/Natural product Origin Part used of administration Active Constituent(s)/extract(s) Activity Side effects/ toxicity Remarks Reference
Ximenia caffra East Root MT Methanol extract Extract concentrations of 2 mg/ ± No signi®cant activity against mycobacteria Fabry et al.,
Sond. (Olacaceae) Africa MA mL allowed the growth of more 1998
(Kenya) MC than 10% of each of the 5
MTe mycobacterial strains
MI and bacterial
strains
Zingiber of®cinale ± Rhizome MT MIC (mg/L) ± 10-Gingerol was the most active compound for Hiserodt et al.,
(Ginger) MA 1 10-gingerol 1 25 (MA) 50 (MT) the inhibition of MA. However this compound 1998
(Zingiberaceae) 2 8-gingerol 2 50 (MA) 50 (MT) was less active against MT
3 6-gingerol isolated from 3 >100 (MA) >100 (MT)
dichloromethane extract
S. M. NEWTON ET AL.

BCG, Bacillus Calmette Guerin; Br C, British Columbia; DMSO, dimethyl sulphoxide; EC, Escherichia coli; Guad, Guadeloupe; IC50 50% inhibitory concentration (concentration required to
inhibit growth of the bacterial population by 50%); INH, isonicotinic acid hydrazide; LC50, 50% lethal concentration (concentration required to kill 50% of the population of organisms); MA,
Mycobacterium avium; MAu, Mycobacterium aurum; MAC, Mycobacterium avium complex; MBC, minimum bactericidal concentration; MC, Mycobacterium chelonae/chelonei; MDR,
multi-drug resistant; MF, Mycobacterium fortuitum; MG, Mycobacterium gordonae; MI, Mycobacterium intracellulare; MIC, minimum inhibitory concentration; MK, Mycobacterium
kansaii; MM, Mycobacterium marinum; MSc, Mycobacterium scrofulaceum; MSi, Mycobacterium simiae; MSm, Mycobacterium smegmatis; MT, Mycobacterium tuberculosis; MTe,
Mycobacterium terrae; MX, Mycobacterium xenopi; SA, Staphylococcus aureus; SLM, Simiae-like mycobacterium; TB, tuberculosis.

Phytother. Res. 14, 303–322 (2000)

 ANTIMYCOBACTERIAL NATURAL PRODUCTS
compounds to inhibit M. tuberculosis within cultured
human macrophages. This may be carried out using the
methodology of Crowle and May (1990).
PLANT SPECIES INVESTIGATED FOR
ANTIMYCOBACTERIAL ACTIVITY
The crude extracts of many plant species, especially those
with ethnomedical uses have been assessed for in vitro
antimycobacterial properties but relatively few active
compounds have been isolated. In many cases, work will
have been discontinued because the extracts exhibited
little or no activity at the highest concentrations tested.
For the purpose of this review, we have selected mostly
those species which have been tested for activity against
one or more species of mycobacteria and which have
been further investigated to determine the nature of the
constituents likely to be responsible for the activity. This
information, summarized in Table 1, has been compiled
mainly from the literature of the last 20–30 years.
An extensive literature search was carried out using the
Science Citation Index of BIDS (Bath Information Data
Services), 1981 to date and PubMed (Medline), 1966 to date.
The keywords used (in various combinations) in the
search were: Plants; Natural; Remedies; Chinese medi-
cine; Traditional; Herbal; Indian medicine; Tuberculosis;
Mycobacteria; Antimycobacterial; Antituberculosis;
Tubercle bacilli.
Furthermore, detailed searches through journals such
as Reviews of Aromatic and Medicinal Plants, for
papers and articles which are not included in the two
databases (BIDS and Medline), were also included.
Note that in some of the studies cited such as those
reported by Cantrell et al., 1998a; Fitzpatrick, 1954;
Grange and Davey, 1990; Lucas et al., 1951, large
numbers of plant species were tested but only those
that appear to have the most potent activities are
included. In addition, a recent article (prepared at the
same time as this present review article) by Lall and
Meyer (1999) has also reported significant antimyco-
bacterial activity of some plants which are not incor-
porated into Table 1. An attempt has been made to
summarize all the relevant information available so that
species can be assessed for their potential as leads to
anti-TB agents. In studies where standard anti-TB drugs
have been used as positive controls, this is indicated in
the remarks column of the table as the results may be
REFERENCES
Abbruzzese MR, Delaha EC, Garagusi VF. 1987. Absence of
antimycobacterial synergism between garlic extract
and antituberculosis drugs. Diag Microbiol Infect Dis 8:
79±85.
Al-Yahya MA, Muhammad I, Mirza HH, El-Feraly FS. 1998.
Antibacterial constituents from the rhizomes of Ferula
communis. Phytother Res 12: 335±339.
Amin AH, Subbaiah TV, Abbasi KM. 1969. Berberine sulfate:
Antimicrobial activity, bioassay and mode of action. Can
J Microbiol 15: 1067±1076.
Boiteau P, Buzas A, Lederer E, Polonsky J. 1949. Derivatives
of Centella asiatica used against leprosy. Nature 163: 258.
Bolton S, Null G, Troetel WM. 1982. The medical uses of
garlicÐfact and ®ction. J Am Pharm Assoc 22: 40±43.
Cantrell CL, Lu T, Fronczek FR, Fischer NH, Adams LB,
Copyright # 2000 John Wiley & Sons, Ltd.
319
more reliable than those from studies where controls
were not included.
PLANT SPECIES AS A SOURCE OF NEW
ANTIMYCOBACTERIAL AGENTS
Compared with microorganisms, plant species have so far
proved disappointing as a source of potent antibacterial
agents. However, as is well illustrated in Table 1, a
number of plant extracts and compounds do have potent
antimycobacterial properties. Examples of the species
which appear to be among the most active include Allium
sativum, Borrichia frutescens, Ferula communis, Her-
acleum maximum, Karwinskia humboldtiana, Leucas
volkensii, Moneses uniflora, Oplopanax horridus, Salvia
multicaulis and Strobilanthus cusia.
In some cases, compounds have been isolated which
have antimycobacterial activities comparable to standard
anti-TB drugs, for example (E)- and (Z)-phytol and
phytanol which were isolated from Leucas volkensii
(Rajab et al., 1998). It is hoped that natural products such
as the latter may prove to be useful agents for TB
treatment or may be lead compounds from which new
drugs may be developed. Bromhexine is a semi-synthetic
derivative of the alkaloid vasicine, which is found in
Adhatoda vasica, an Indian shrub that has long been used
in India for the treatment of TB. Although bromhexine
and its metabolite ambroxol have been widely used as
mucolytics, these compounds exert a pH dependent
inhibitory effect against M. tuberculosis in vitro and they
are also concentrated in macrophages. It is suggested that
they may be useful as adjucts in TB therapy (Grange and
Snell, 1996).
CONCLUSION
The data compiled in Table 1 reveal that extracts of
plant species from a wide range of families have been
shown to have significant in vitro antimycobacterial
activities and that a number of active plant-derived
compounds belonging to various chemical classes have
been isolated. These findings should stimulate the search
for novel natural product leads towards new anti-TB
agents.
Franzblau SG. 1996. Antimycobacterial cycloartanes from
Borrichia frutescens. J Nat Prod 59: 1131±1136.
Cantrell CL, Fischer NH, Urbatsch L, McGuire MS, Franzblau
SG. 1998a. Antimycobacterial crude plant extracts from
South, Central, and North America. Phytomedicine 5:
137±145.
Cantrell CL, Nunez IS, Castaneda-Acosta J, et al. 1998b.
Antimycobacterial activities of dehydrococtus lactone
and its oxidation products. J Nat Prod 61: 1181±1186.
Cantrell CL, Rajab MS, Franzblau SG, Fischer NH. 1999a.
Antimycobacterial triterpenes from Melia volkensii. J Nat
Prod 62: 546±548.
Cantrell CL, Abate L, Fronczek FR, Franzblau SG, Quijano L,
Fischer NH. 1999b. Antimycobacterial eudesmanolides
Phytother. Res. 14, 303–322 (2000)
320 S. M. NEWTON ET AL.
from Inula helenium and Rudbeckia subtomentosa.
Planta Med 65: 351±355.
Chang PWH. 1948. Chin Med J 67: 648; 11. per Wang VFL.
1950. In vitro antibacterial activity of some common
Chinese herbs on Mycobacterial tuberculosis. Chin Med J
(Engl) 68: 169±172.
Chang MW, Tasaka H, Kuwabara M, Watanabe T, Matsuo Y.
1979. Effects of Panax ginseng on the growth of
Mycobacterium tuberculosis H37Rv. Hiroshima J Med
Sci 28: 115±118.
Chiang C, Chang FC. 1973. Tetracyclic triterpenoids from
Melia azadarach, L.-III. Tetrahedron 29: 1911±1929.
Chung AC, Aktar Z, Jackson S, Duncan K. 1995. A
high throughput screen for detecting novel antimyco-
bacterial agents. Antimicrob Agents Chemother 39: 2235±
2238.
Crowle AJ, May MH. 1990. Inhibition of tubercle bacilli in
cultured human macrophages by chloroquine used alone
and in combination with streptomycin, isoniazid, pyrazi-
namide and two metabolites of vitamin D. Antimicrob
Agents Chemother 34: 2217±2222.
Delaha EC, Garagusi VF. 1985. Inhibition of mycobacteria by
garlic extract (Allium sativum). Antimicrob Agents Che-
mother 27: 485±486.
Dymock W, Warden C, Hooper D. 1893. Pharmacographia
Indica. A History of the Principal Drugs of Vegetable
Origin Met within a British India, Vol 3, Kegan, Paul,
Trench, Trubner and Co.: London, 49±51; 18.
El Sayed KA, Hamann MT, Abd El-Rahman HA, Zaghloul AM.
1998. New pyrrole alkaloids from Solanum sodomaeum.
J Nat Prod 61: 848±850.
Fabry W, Okemo PO, Ansorg R. 1998. Antibacterial activity of
East African medicinal plants. J Ethnopharmacol 60: 79±
84.
Fischer NH, Lu T, Cantrell CL, Casteneda-Acosta J, Quijano L,
Franzblau SG. 1998. Antimycobacterial evaluation of
germacranolides. Phytochemistry 49: 559±564.
Fitzpatrick FK. 1954. Plant substances active against
Mycobacterium tuberculosis. Antibiot Chemother 4: 528±
536.
Fournet A, Hoquemillar R, Roblot F, Cave A, Richomme P,
Bruneton J. 1993. Les chimanines, nouvelles quinoleines
substituees en 2, isoleesd'une plante bolivienne anti-
parasitaire: Galipea longi¯ora. J Nat Prod 56: 1547±
1552.
Fournet A, Barrios AA, Munoz V et al. 1994. Antiprotozoal
activity of Quinoline alkaloids isolated from Galipea
longi¯ora, a Bolivian plant used as a treatment for
cutaneous Leishmaniasis. Phytother Res 8: 174±178.
Fournet A, Ferreira ME, Dearias AR et al. 1996. Sapriolactone,
a cytotoxic norditerpene from Salvia prionitis. Antimicrob
Agents Chemother 40: 2447±2451.
Frame AD, Rios-Olivares E, De Jesus L, Ortiz D, Pagan J,
Mendez S. 1998. Plants from Puerto Rico with anti-
Mycobacterium tuberculosis properties. P R Health Sci J
17: 243±252.
Gabbrielli G, Loggini F, Cioni PL, Giannaccini B, Mancuso E.
1988. Activity of lavandino essential oil against non-
tubercular rapid grown mycobacteria. Pharmacol Res
Commun 20 (Suppl. 5): 37±40.
Gentry EJ, Jampani HB, Keshavarz-Shokri A et al. 1998.
Antitubercular natural products: Berberine from the roots
of commercial Hydrastis canadensis powder. Isolation of
inactive 8-oxotetrahydrothalifendine, canadine, b-hydras-
tine, and two new quinic acid esters, hycandinic acid
esters-1 and -2. J Nat Prod 61: 1187±1193.
Ghosal S, Chaudhuri RK. 1975. Chemical constituents of
Gentianaceae XVI: antitubercular activity of xanthones
of Canscora decussata Schult. J Pharm Sci 64: 888±
889.
Ghosal S, Biswas K, Chaudhuri RK. 1978. Chemical constitu-
ents of Gentianaceae XXIV: Anti-Mycobacterium tuber-
culosis activity of naturally occurring xanthones and
synthetic analogs. J Pharm Sci 67: 721±722.
Gomez-Flores R, Gupta S, Tamez-Guerra R, Mehta RT. 1995.
Determination of MICs for Mycobacterium avium±M.
intracellulare complex in liquid medium by a colorimetric
method. J Clin Microbiol 33: 1842±1846.
Gordon S, Houldsworth S, Duncan K, Roberts IS, Andrew PW.
Copyright # 2000 John Wiley & Sons, Ltd.
1996. Rapid measurement of antimycobacterial drug
activity. Res Microbiol 147: 79±86.
Gottshall RY, Lucas EH, Lickfeldt A, Roberts JM. 1949. The
occurrence of antibacterial substances active against
Mycobacterium tuberculosis in seed plants. J Clin Invest
28: 920±921.
Grange JM, Davey RW. 1990. Detection of antituberculous
activity in plant extracts. J Appl Bacteriol 68: 587±591.
Grange J, Snell N. 1996. Activity of bromhexine and
ambroxol, semi-synthetic derivatives of vasicine from
the Indian shrub Adhatoda vasica, against Mycobac-
terium tuberculosis in vitro. J Ethnopharmacol 50: 49±
53.
Herbert D, Paramasivan CN, Prabhakar R, Swaminathan
G. 1994. In vitro experiments with Centella asiatica:
investigation to elucidate the effect of an indigenously
prepared powder of this plant on the acid-fastness and
viability of M. tuberculosis. Indian J Lepr 66: 65±68.
Hiserodt RD, Franzblau SG, Rosen RT. 1998. Isolation of 6-,8-,
and 10-gingerol from ginger rhizome by HPLC and
preliminary evaluation of inhibition of Mycobacterium
avium and Mycobacterium tuberculosis. J Agric Food
Chem 46: 2504±2508.
Horne N. 1996. Tuberculosis and other mycobacterium
diseases. In Mansons Tropical Diseases, 20th edn, Cook
FEG (ed). WB Saunders: London; 971±1015.
Houghton PJ, Woldemariam TZ, Watanabe Y, Yates M. 1999.
Activity against Mycobacterium tuberculosis of alkaloid
constituents of angostura bark, Galipea of®cinalis. Planta
Med. 65: 250±254.
Ingolfsdottir K, Chung GAC, Skulason VG, Gissurarson SR,
Vilhelmsdottir M. 1998. Antimycobacterial activity of
lichen metabolites in vitro. Eur J Pharm Sci 6: 141±144.
Jain RC. 1998. Anti-tubercular activity of garlic oil. Indian J
Pathol Microbiol 41: 131.
Kakkar KK. 1988. MandukapamiÐMedicinal uses and ther-
apeutic ef®cacy. Indian Drugs 26: 92±96; 42.
Kariyone T, Kimura Y. 1962. Japanese and Chinese Medicinal
Plants (in Japanese), 3rd edn. Hirokawa: Tokyo, 250±290;
43. per Roper R, Ma TS. 1968. Microchemical investiga-
tion of medicinal plants. II. The antitubercular activity of
some plant acids and their hyrazides. Mikrochimica Acta
(Wien): 212±218.
Kobaisy M, Abramowski Z, Lermer L, Saxena G, Hancock
REW, Towers GHN. 1997. Antimycobacterial Polyynes of
Devil's Club (Oplopanax horridus), a North American
native medicinal plant. J Nat Prod 60: 1210±1213.
Kokwaro JO. 1976. Medicinal Plants of East Africa. East
African Literature Bureau: Nairobi, Kenya; 157.
Lall N, Meyer JJM. 1999. In vitro inhibition of drug resistant
and drug sensitive strains of Mycobacterium tuberculosis
by ethnobotanically selected South African plants. J
Ethnopharmacol 66: 347±354.
Leite CQF, Moreira RRD, Neto JJ. 1998. Action of Eucalyptus
oils against Mycobacterium avium. Fitoterapia LXIX: 282±
283.
Lin L-Z, Wang X-M, Huang X-I, Huang Y, Cordell GA. 1989.
In vitro ef®ciency of oral and intralesional administration
of 2-substituted quinolines in experimental treatment of
new world cutaneous leishmaniasis caused by Leishma-
nia amazonensis. Phytochemistry 28: 3542±3543.
Li Shih-Chen. 1930. Compendium of Materia Medica (in
Chinese), 1st edn, Naking, 1593; revised and reprinted.
Shanghai: Commercial Press; 49. per Roper R, Ma TS.
1968. Microchemical investigation of medicinal plants. II.
The antitubercular activity of some plant acids and their
hyrazides. Mikrochimica Acta (Wien): 212±218.
Lu T, Vargas D, Franzblau SG, Fischer NH. 1995. Diterpenes
from Solidago rugosa. Phytochemistry 38: 451±456.
Lu T, Cantrell CL, Robbs SL, Franzblau SG, Fischer NH. 1998.
Antimycobacterial matricaria esters and lactones from
Astereae species. Planta Med 64: 665±667.
Lucas EH, Lickfeldt A, Gottshall RY, Jennings JC. 1951. The
occurrence of antibacterial substances in seed plants
with special reference to Mycobacterium tuberculosis.
Bull Torrey Bot Club 78: 310±321.
Ma TS, Roper R. 1968. Microchemical investigation of
medicinal plants. I. The antitubercular principle in Prunus
mume and Schizandra chinensis. Mikrochimica Acta
(Wien): 167±181.
Phytother. Res. 14, 303–322 (2000)
 ANTIMYCOBACTERIAL NATURAL PRODUCTS
McChesney JD. 1995. The promise of natural products for the
development of new pharmaceuticals and agrochem-
icals. In Chemistry of the Amazon Symposium Series,
American Chemicals Society: D.C.; 54.
McCutcheon AR, Stokes RW, Thorson LM, Ellis SM, Hancock
REW, Towers GHN. 1997. Antimycobacterial screening of
British Columbian medicinal plants. Int J Pharmacog 35:
77±83.
Mitscher LA, Gollapudi SR, Oburn DS, Drake S. 1985.
Antimicrobial agents from higher plants: Two dimethyl-
benzisochromans from Karawinskia humboldtiana. Phy-
tochemistry 24: 1681±1683.
Mitscher LA, Baker W. 1998a. Tuberculosis: A search for
novel therapy starting with natural products. Med Res
Rev 18: 363±374.
Mitscher LA, Baker WR. 1998b. A search for novel che-
motherapy against tuberculosis amongst natural pro-
ducts. Pure Appl Chem 70: 365±371.
Moerman DE. 1986. Medicinal Plants of Native America II,
Ann Arbor, Michigan, USA, 642.
Moreira RRD, Anno IS, Leite CQF. 1997. Sensitivity of
mycobacteria to different species of Eucalyptus L'Herit.
Rev Microbiol 28: 256±260.
Muhammad I, Mossa JS, El-Feraly FS. 1992. Antibacterial
diterpenes from the leaves and seeds of Juniperus
excelsa M. Bieb. Phytother Res 6: 261±264.
Muhammad I, Mossa JS, El-Feraly FS. 1996. Additional
antibacterial diterpenes from the bark of Juniperus
procera. Phytother Res 10: 604±607.
Nikulin IM, Lisitsyna LY, Tikhonov AI, Shcherbina VD,
Stebliuk PN. 1979. Propolis in the treatment of in¯amma-
tory diseases of the airways. Zhurnal Ushnykh Nosovykh
I. Gorlovykh Boleznei (Kiev) Nov-Dec, 9±12 (in Russian
with English summary); 64. per Grange JM, Davey RW.
1979. Propolis in the treatment of in¯ammatory diseases
of the airways. Zhurnal Ushnykh Nosovykh I. Gorlovykh
Boleznei (Kiev) Nov-Dec, 9±12 (in Russian with English
summary); 64. per Grange JM, Davey RW. 1990. Detec-
tion of antituberculous activity in plant extracts. J Appl
Bacteriol 68: 587±591.
Ochi M, Kotsuki H, Tokoroyama T, Kubota T. 1977. Bull Chem
Soc Jpn 50: 2499±2500; 65. per Cantrell CL, Rajab MS,
Franzblau SG, Fischer NH. 1977. Bull Chem Soc Jpn 50:
2499±2500.
Okunade AL, Wiemer DF. 1985. Ant-repellent sesquiterpene
lactones from Eupatorium quadrangulare. Phytochemis-
try 24: 1199±1201.
Oosterhuis B, Storm G, Cornelissen P, Su C, Sollie F,
Jonkman J. 1993. Dose dependent uricosuric effect of
ambroxol. Eur J Clin Pharm 44: 237±241.
Preininger V. 1975. In The Alkaloids; Manske RHF (ed.)
Academic Press: New York: 15: 231±236.
Rahman S, Fukamiya N, Okano M, Tagahara K, Lee KH. 1997.
Antituberculosis activity of quassinoids. Chem Pharm
Bull 45: 1527±1529.
Rajab MS, Cantrell CL, Franzblau SG, Fischer NH. 1998.
Antimycobacterial activity of (E)-phytol and derivatives:
A preliminary structure±activity study. Planta Med 64:
2±4.
Rastogi N, Abaul J, Goh KS, Devallois A, Philogene E,
Bourgeois P. 1998. Antimycobacterial activity of chemi-
cally de®ned natural substances from the Caribbean ¯ora
in Guadeloupe. FEMS Immuno. Med. Microbiol 20: 267±
273.
Reddi GS, Shukla NP, Singh KV. 1986. Chemotherapy of
tuberculosis. Antitubercular activity of Ocimum sanctum
leafy extract. Fitoterapia LVII: 114±116.
Roper R, Ma TS. 1968. Microchemical investigation of
medicinal plants. II. The antitubercular activity of some
plant acids and their hyrazides. Mikrochimica Acta
(Wien): 212±218.
Satim DF, Washington JA II. 1991. Antibacterial susceptibility
tests: dilution methods. In Manual of Clinical Micro-
biology, 5th edn. Balows A (ed.) American Society for
Microbiology: Washington, DC: 1105±1116.
Spath E, Pikl J. 1930. Monatsh Chem 55: 352±357; 75. per
Houghton PJ, Woldemariam TZ, Watanabe Y, Yates M.
1999. Activity against Mycobacterium tuberculosis of
alkaloid constituents of angostura bark, Galipea of®cina-
lis. Planta Med 65: 250±254.
Copyright # 2000 John Wiley & Sons, Ltd.
321
Subbaiah TV, Amin AH. 1967. Effect of berberine sulphate on
Entamoeba histolytica. Nature 215: 527±528.
Sun D, Abraham SN, Beachy EH. 1988. In¯uence of berberine
sulfate on synthesis and expression of ®mbrial adhesin in
uropathogenic Escherichia coli. Antimicrob Agents Che-
mother 32: 1274±1277.
Turner NJ. 1982. Traditional use of Devil's-club (Oplopanax
horridus; Araliaceae) by native peoples in Western North
America. J Ethnobiol 1: 17±38.
Turner NJ, Thompson L, York A. 1990. Thompson Ethnobo-
tany; Royal British Columbia Museum Memoir No.3;
Royal British Columbia Museum: Victoria, B.C., 44±45, 47,
49; per Kobaisy M, Abramowski Z, Lermer L, Saxena G,
Hancock REW, Towers GHN. 1997. Antimycobacterial
Polyynes of Devil's Club (Oplopanax horridus), a North
American native medicinal plant. J Nat Prod 60: 1210±
1213.
Ulubelen A, Evren N, Tuzlaci E, Johansson C. 1988.
Diterpenoids from the roots of Salvia hypargeia. J Nat
Prod 51: 1178±1183.
Ulubelen A, Topcu G, Bozok Johansson C. 1997.
Norditerpenoids and diterpenoids from Salvia multi-
caulis with antituberculous activity. J Nat Prod 60:
1275±1280.
Usher G. 1974. A Dictionary of Plants Used by Man.
Macmillan: New York; 82.
Valcic S, Montenegro G, Mujica AM et al. 1999. Phyto-
chemical, morphological and biological investigations
of propolis from central Chile. Z Naturforsch 54: 406±
416.
Van Puyvelde L, Pagezy H, Kayonga A. 1975. Plantes
medicinales et toxiques du Rwanda (I). Afrique Medicale
14: 925±930; 84. per Van Puyvelde L, Ntawukiliyayo JD,
Portaels F, Hakizamungu E. 1975. Plantes medicinales
et toxiques du Rwanda (I). Afrique Medicale 14: 925±
930; 84. per Van Puyvelde L, Ntawukiliyayo JD, Portaels
F, Hakizamungu E. 1994. In vitro inhibition of myco-
bacteria by Rwandese medicinal plants. Phytother Res 8:
65±69.
Van Puyvelde L, Ngaboyisonga M, Rwangabo PC, Mukar-
ugambwa S, Kayonga A, Runyinya-Barabwiliza. 1977.
Enquetes Ethnobotaniques sur la Medecine Tradion-
nelle. Tome 1: Prefecture de Kibuye U.N.R., Butare;
85. per Van Puyvelde L, Ntawukiliyayo JD, Portaels F,
Hakizamungu E. 1994. In vitro inhibition of myco-
bacteria by Rwandese medicinal plants. Phytother Res
8: 65±69.
Van Puyvelde L, Rwangabo PC, Barabwiliza-Runyinya
Ayobangira FX, Mungarulire J. 1982. Plantes medici-
nales et toxiques du Rwanda (iii). Afrique Medicale 21:
401±404; 86. per Van Puyvelde L, Ntawukiliyayo JD,
Portaels F, Hakizamungu E. 1982. Plantes medicinales et
toxiques du Rwanda (iii). Afrique Medicale 21: 401±404;
86. per Van Puyvelde L, Ntawukiliyayo JD, Portaels F,
Hakizamungu E. 1994. In vitro inhibition of myco-
bacteria by Rwandese medicinal plants. Phytother Res
8: 65±69.
Van Puyvelde L, Ntawukiliyayo JD, Portaels F, Hakizamungu
E. 1994. In vitro inhibition of mycobacteria by Rwandese
medicinal plants. Phytother Res 8: 65±69.
Vartia KO. 1973. Antibiotics in lichens. In The Lichens.
Ahmadijian V, Hale ME (eds). Academic Press: New York;
547±561; 88. per Ingolfsdottir K, Chung GAC, Skulason
VG, Gissurarson SR, Vilhelmsdottir M. 1998. Antimyco-
bacterial activity of lichen metabolites in vitro. Eur J
Pharm Sci 6: 141±144.
Vieira PC, Kubo I. 1990. Molluscicidal quinoline alkaloids
from Galipea bracteata. Phytochemistry 29: 813±815.
Wachter GA, Franzblau SG, Montenegro G et al. 1998. A new
antitubercular mulinane diterpenoid from Azorella
madreporica Clos. J Nat Prod 61: 965±968.
Wang VFL. 1950. In vitro antibacterial activity of some
common Chinese herbs on Mycobacterial tuberculosis.
Chin Med J (Engl) 68: 169±172.
World Health Organization. 1993 92. per Besra GS, Brennan
PJ. 1997. The mycobacterium cell envelope: a target for
novel drugs against tuberculosis. J Pharm Pharmacol 49
(Suppl.1): 25±30.
Phytother. Res. 14, 303–322 (2000)
322 S. M. NEWTON ET AL.

Wren RC. 1988. Potters New Cyclopaedia of Botanical Drugs
and Preparations. Revised by Williamson EM, Evans FJ.
CW Daniel Co: Saffron Walden.
Yajko DM, Madej JJ, Lancaster MV et al. 1995. Colorimetric
method for determining MICs of antimicrobial agents for
Mycobacterium tuberculosis. J Clin Microbiol 33: 2324±
2327.
Yuang S. 1954. Garlic. Chin J Med (Engl. Ed) 2: 254; 95. per
Delaha EC, Garagusi VF. 1985. Inhibition of mycobacteria
by garlic extract (Allium sativum). Antimicrob Agents
Chemother 27: 485±486.
Zumla A, Grange J. 1998. Clinical review: Tuberculosis. B M J
316: 1962±1964.

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