Journal of Medicinal Plants Research Vol. 5(31), pp.

6885-6889, 23 December, 2011

Available online at http://www.academicjournals.org/JMPR
ISSN 1996-0875 2011 Academic Journals
DOI: 10.5897/JMPR11.1425

Full Length Research Paper

Alternate therapy of Type 2 diabetes mellitus (T2DM)

with Nigella (Ranunculaceae)
M. S. H. Akash1, K. Rehman1, F. Rasool2, A. Sethi3, M. A. Abrar4, A. Irshad5, A. Abid6
and G. Murtaza7*
1

Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang
University Hangzhou (PR) China.
2
University College of Pharmacy, the University of Punjab, Lahore, Pakistan.
3
Department of Pharmacy, GC University, Faisalabad, Pakistan.
4
Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
5
Department of Agriculture, Bahauddin Zakariya University, Multan, Pakistan.
6
Institute of Pure and Applied Biology, Bahauddin Zakariya University, Multan, Pakistan.
7
Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Accepted 8 November, 2011

Type 2 diabetes mellitus (T2DM) is being more incurable due to its complex patho-physiology and
failure of conventional anti-diabetic agents to restore the normal architecture and morphology of
pancreatic islets and some potential side effects and weight gain. Many agents of plant origin have
been used as anti-diabetic agents since ancient time. Among them Nigella sativa L. (Ranunculaceae) is
being more popular day by day due to its potential and broad spectrum effects on many diseases but
unfortunately, no sufficient scientific data is available. A comprehensive literature (in English only)
search was conducted using electronic databases: Medline (1966 to 2010) and EMBASE (1980 to 2010).
For a simple search, initially the search terms used were anti-diabetic agent, and N. sativa, for each
search term separately, and then an advanced search was made by combining all search fields in
abstract, key words, or title. Recently, a lot of work has been done for the evaluation of anti-diabetic
(against type-II diabetes) effect of N. sativa, significant results have been achieved. However, further
studies are required to investigate the anti-diabetic (against type-II diabetes) of N. sativa at molecular
levels.
Key words: Anti-diabetic agent, in vitro analysis, in vivo studies.
INTRODUCTION
Type 2 diabetes mellitus (T2DM) is characterized by the
hyperglycemia, dyslipidemia and imbalanced proinflammatory/oxidative mediators along with various
transcriptional pathways that decisively provoke the
impairment of pancreatic islets and their apoptosis, and
ultimately overt diabetes, and affects millions of people
every year. The prevalence of diabetes is increasing
worldwide (Wild et al., 2004) and among the cases of

*Corresponding author. E-mail: gmdogar356@gmail.com. Tel:

92-314-2082826. Fax: 92-992-383441.

diabetes make a diagnosis, more than 95% are T2D

(Sachdeva et al., 2009), and it is unspecified that if its
pervasiveness is not stopped properly then it may have
an effect on more than 366 million population in 2030
(Wild et al., 2004). It is one of the 5 major causes of the
death in the world (Rahimi et al., 2005). Among various
factors that are being involved in the progression of
T2DM, oxidative stress plays its crucial role in the
etiology of diabetes and diabetic complications (Noor et
al., 2008; Prasad et al., 2009) and it not only damage
function of islets but also demolish them (Martim et al.,
2003). From various studies performed on alloxan or
streptozotocin (STZ) induced diabetic rats and mice

6886

J. Med. Plants Res.

(Bhatti et al., 2009) and some diabetic patients, high

insensitivity of oxidative stress due to persistent and
chronic hyperglycemia, deplete the activity of antioxidative defense mechanism by promoting the
generation of free radicals (Baynes, 1991). STZ induced
diabetic animals have also been used to investigate the
effect of diabetes on the induction of neuropathy
(Jakobsen and Lundbaek, 1976; Sharma et al., 1977),
and certain interactive pathogenic mechanisms of
diabetic peripheral nephropathy have been developed
both in human and experimental animal models, and
chronic hyperglycemia have been considered as primary
risk factor for the induction of nephropathy. This chronic
hyperglycemia could augment the enhanced oxidative
stress, increased aldose reductase activity (Cameron et
al., 1997), and cause the accumulation of advance
glycation end products (Karachalias et al., 2003).
Majority of infections are at the epidemic levels in the
world, although a variety of drugs have been discovered
from natural source or are being synthesized in the
laboratories for the treatment of these chronic diseases
but their side or adverse effects are overall off-putting the
clinical uses of these medicines. For its traditional
therapy, many agents of plant origin along with synthetic
agents are also being used for the treatment of T2DM
(Arayne et al., 2007). According to the world
ethnobotanical report, almost 800 plants posses
antidiabetic potential (Alarcon-Aguilara et al., 1998) and
due to known potential, known complications such as
known toxicity (Kahn et al., 2006; Alvarsson et al., 2008;
Yki-Jrvinen, 2004) and weight gain during therapy
(DeFronzo et al., 2011; McFarlane, 2009; Purnell and
Weyer, 2003; Bonora, 2007; Mitri and Hamdy, 2009) with
conventional anti-diabetic agents, research has been
focused on scientific evaluation of traditional drugs of
plant origin and trying to screen out more effective and
safe hypoglycemic agents (Arayne et al., 2007), and
open new door for the investigators and researchers to
think about these traditional anti-diabetic plants with
histories thousands years back due to their traditional
uses when synthetic agents have not been invented. Yet
in developing countries, almost 80% population still use
these plants in primary medical problems (Grover and
Yadav, 2004; Paarakh, 2010) and such remedies remain
important in many developing and developed countries
despite the lack of scientific study. Since 1980, World
Health Organization (WHO) has started to encourage
countries to investigate these traditional medical plants,
however, evaluation of their active constituents has also
open immense area for research and development
(Paarakh, 2010).
MATERIALS AND METHODS
A comprehensive literature (in English only) search was conducted
using electronic databases: Medline (1966 to 2010) and EMBASE
(1980 to 2010). For a simple search, initially the search terms used

were anti-diabetic agent, and Nigella sativa, for each search

term separately, and then an advanced search was made by
combining all search fields in abstract, key words, or title. To make
certain a comprehensive review, investigation of literature was
supplemented by probing the reference lists of the papers created
from the original investigations. The authors selected the potentially
appropriate papers identified by the electronic searches. The
published literature eligible for inclusion were reviewed, in vitro and
in vivo studies and the randomized trials are presented in English
language. All the literature selected was confirmed for duplications,
which, if observed were excluded.

RESULTS
Nigella sativa
N. sativa L. (Ranunculaceae) is a herbal plant known as
black cumin (Arayne et al., 2007), most commonly
cultivated in Europe, Middle East and Asia, and is most
commonly used as traditional medicine in Arabian
countries, the subcontinent and Europe (Sayed, 1980). In
subcontinent, it is known as Kalonji or kalajeera while in
China it is referred as Hak Jung Chou (Mathur et al.,
2011). Recently, its pharmacological and potential
therapeutic activities have also been proved for the
treatment of many diseases such as bronchodilatation,
immunomodulative (El-Kadi and Kandil, 1987), antibacterial (Hanafy and Hatem, 1991), hypotensive (Zaoui
et al., 2000), hepatoprotective (Kanter et al., 2003,
2005a), gastroprotective (Kanter et al., 2005b),
antihistaminic and anti-oxidative (Kanter et al., 2006a)
and neuroprotective (Kanter et al., 2006b). According to
Islam, it can cure all diseases except death (Paarakh,
2010). Even though, this plant has many beneficial
effects to avert many chronic diseases but unfortunately,
these effects have not been satisfactorily scrutinized.
Only limited studies are available for the use of N. sativa
as anti-diabetic agent in some diabetic patients to
maintain the normoglycemia (Tahraoui et al., 2007;
Otoom et al., 2006), and also there is no sufficient data
available about the effect of N. sativa on the diabetic
induced complications and syndromes.
Anti-diabetic properties of Nigella sativa
N. sativa is being used as antidiabetic agent since
ancient time but unfortunately, no one has ever focus on
this plant to study how and under which mechanism,
could cause the normoglycemia. Recently, in this decade,
numerous
studies
have
been
performed
on
experimentally induced diabetic animals (Mathur et al.,
2011) to check its effects on diabetes and confirmed that
this plant has also anti-diabetic activity as it reduced the
significant levels of blood glucose in these animals
(Fararh et al., 2002, Rchid et al., 2004, Kaleem et al.,
2006; Kanter et al., 2003). These anti-diabetic properties
of N. sativa plant are due to insulinotropic action (Fararh
et al., 2002; Rchid et al., 2004), anti-oxidant properties

Akash et al.

(Kanter et al., 2003, 2004; Altan et al., 2007; Ilaiyaraja

and Khanum, 2010), hepatic gluconeogenesis inhibition
(El-Dakhakhny et al., 2002; Fararh et al., 2004; Pari and
Sankaranarayanan, 2009). N. sativa exhibits its
antioxidative effects by the inhibition of eicosanoid
generation and membrane lipid peroxidation (Ilaiyaraja
and Khanum, 2010).
Several studies have also been performed to confirm
its effects on insulin sensitivity and release (Fararh et al.,
2002; Kanter et al., 2004; Benhaddou-Andaloussi et al.,
2008, 2010). Recently, some studies have also been
conducted on N. sativa and, they proposed that this plant
improves insulin sensitivity by preventing the intensity of
oxidative stress (Bloch-Damti and Bashan, 2005; Houstis
et al., 2006; Song et al., 2007). From the results of
homeostasis model assessment which is a computer
aided program, it has been observed that N. sativa
improves insulin sensitivity in peripheral tissues and
enhances its secretion in the -cells of pancreatic islets
(Kanter, 2008; Bamosa et al., 2010; Sankaranarayanan
and Pari, 2011), because it had been proposed that N.
sativa has the ability to restore the structural integrity of
the pancreatic islets in diabetic rats (El-Zawahrawy and
Al-Zahrra, 1998) and STZ induced diabetic rats (Kanter,
2008),
and later some histopathological
and
immunohistochemical studies has been performed in
order to investigate the architecture of pancreatic islets
and observed that N. sativa has the ability to recover the
integrity of -cells of pancreatic islets (BenhaddouAndaloussi et al., 2008, 2010; Kanter et al., 2009).
Insulin secretory effects of N. sativa have also been
checked on in vitro isolated rat pancreatic islets in the
presence of 8.3 mmol/L glucose and observed that
secretion of insulin is increased in the presence of N.
sativa (Rchid et al., 2004, Benhaddou-Andaloussi et al.,
2008, 2010). It has been proposed from previous studies
that reactive oxygen species (ROS) are generated by
chronic exposure of hyperglycemia and that ROS are
directly neurotoxic and promotes neuronal apoptosis (Luo
et al., 1998; Kanter, 2008). N. sativa also has the ability
to abate the diabetes associated complications, like
diabetic nephropathy (Kanter, 2008). Results of these
studies show that N. sativa has antidiabetic properties by
different mechanisms (Benhaddou-Andaloussi et al.,
2010).
In vitro and in vivo studies on Nigella sativa
Various in vitro and in vivo studies have also been
conducted in order to confirm its antidiabetic effects on
T2DM and diabetes associated complications but
unfortunately on body the novel techniques used in order
to find out its effects at molecular levels in different
diseases. Conventional studies have been performed to
confirm its traditional claimed effects. As we now know
that T2DM is becoming more fatal disease, conventional

6887

therapies have failed due to some side effects (Kahn et

al., 2006; Alvarsson et al., 2008; Yki-Jrvinen, 2004; Li et
al., 2003) and weight gain problems with some
antidiabetic agents (DeFronzo et al., 2011, McFarlane
2009, Purnell, 2003; Bonora, 2007; Mitri and Hamdy,
2009), from now, we need such therapeutic agent which
not only abate the infuriating effects of inducers of T2DM
but also do not cause the weight gain during therapy.
Various experimental studies have also been performed
on N. sativa in order to point out any kind of cytotoxicity.
However, some possible cytotoxicity had been noted
(Khader et al., 2007; Ilaiyaraja and Khanum, 2010) which
does not induce weight gain during therapy (Kanter
2008), thus, this drug will act as palliative for large
number of chronic diseases and syndromes. Latest
techniques are required to investigate the traditional
effects of N. sativa on T2DM, diabetes induced
complications and syndromes such as diabetic induced
neuropathy and nephropathy. There is also need to
investigate either N. sativa acts as therapeutic agent or
its active constituent thymoquinone, induces its
therapeutic activity.
Cross sectional survey and clinical trial of Nigella
sativa
In south-eastern Morocco, N. sativa has been traditionally
used for the treatment of diabetes and hypertension
(Tahraoui et al., 2007), and in one cross sectional survey
of 310 diabetic patients in Jorden, 7.3% were revealed to
use N. sativa to treat diabetes (Otoom et al., 2006).
Recently, a double blind placebo controlled experimental
trial was conducted in Indonesia and it was observed that
N. sativa has the ability to significantly decrease the body
weight but due to low dose, fasting of blood glucose
along with lipid profile was not significant (Datau et al.,
2010), and it has also been used in clinical trials for
diseases other than diabetes (Mathur et al., 2011). Since
this plant has no toxicity of kind (Otoom et al., 2006;
Bloch-Damti and Bashan, 2005), it does not induce the
weight gain during therapy (Kanter, 2008) and it is being
used as therapeutic agent for many diseases, and from
the last decade, various studies are also being conducted
to confirm its traditional effects on different diseases.
T2DM is manifestation of an autoinflammatory
syndrome (Dinarello, 2011; Donath et al., 2008) which is
usually associated with the state of low-grade
inflammation in intra-islets (Holberg and Hotamisligil,
2006; Wellen and Hotamisligil, 2005). This low-grade
inflammation is characterized by various factors such as
IL-1, TNF-, IL-1 dependent cytokines and chemokines,
elevated NF-KB activity, leptin, immune cells infiltration,
amyloid deposits and fibrosis (Donath et al., 2008,
Holberg and Hotamisligil, 2006; Wellen and Hotamisligil,
2005) and induces the -cells dysfunction and apoptosis
of these -cells (Donath and Halban, 2004). So it is better

6888

J. Med. Plants Res.

way to use those agents that have the ability to abate this
inflammation. It has been proved that N. sativa has antiinflammatory properties (AL-Ghambi, 2001; Ali and
Blunden, 2003; Tekeoglu et al., 2007) but this antiinflammatory property of N. sativa to reduce the intra-islet
inflammation still needs to be confirmed, but it has been
confirmed that thymoquinone the active constituent of N.
sativa has the ability to reduce TNF- and IL-L1 in
rheumatoid arthritis (Salem, 2005; Tekeoglu et al., 2007)
N. sativa has antioxidant properties and due to this effect,
it improves glycemia (Kanter, 2008) but further studies
are also needed to investigate if N. sativa has ability to
reduce pro-inflammatory cytokines which are the main
inducers of T2DM or not and if it has, then, which
mechanism is involved to reduce these pro-inflammatory
cytokines. So, we suggest that molecular level studies
are needed to confirm its broad spectrum effects not only
on T2DM but on various diseases in which N. sativa is
traditionally used as palliative to cure these diseases.

Conclusion
Anti-diabetic effects of N. sativa has been studied in the
recent years and satisfactory results have obtained but
still, it is unclear under what exactly mechanism, it averts
the symptoms of diabetes. Furthermore, pre-clinical and
clinical trials are needed to confirm its exact mechanism
against T2DM.
REFERENCES
Alarcon-Aguilara FJ, Roman-Ramos R, Perez-Gutierrez S, AguilarContreras A, Contreras-Weber CC, Flores-Saenz JL (1998). Study of
the anti-hyperglycemic effect of plants used as antidiabetics. J.
Ethnopharmacol., 61: 101-110.
Al-Ghambi MS (2001). Anti-inammatory, analgesic and antipyretic
activity of Nigella sativa. J. Ethnopharmacol., 76: 45-48.
Ali BH, Blunden G (2003). Pharmacological and Toxicological
Properties of Nigella sativa. Phytother. Res., 17: 299-305.
Altan MF, Kanter M, Donmez S, Kartal ME, Buyukbas S (2007).
Combination therapy of Nigella sativa and human parathyroid
hormone on bone mass, biomechanical behavior and structure in
streptozotocin-induced diabetic rats. Acta Histochem., 109: 304-314.
Alvarsson M, Arayne MS, Sultana N, Mirza AZ, Zuberi MH, Siddiqui FA
(2007). In vitro hypoglycemic activity of methanolic extract of some
indigenous plants. Pak. J. Pharm. Sci., 20: 261-268.
Bamosa AO, Kaatabi H, Lebda FM, Elq AMA, Sultan AA (2010). Effect
of Nigella sativa seeds on the glycemic control of patients with type 2
diabetes. Indian J. Physiol. Pharmacol., 54: 344-354.
Baynes JW (1991). Role of oxidative stress in development of
complications in diabetes. Diabetes, 40: 405-412.
Benhaddou AA, Martineau LC, Spoor D, Vuong T, Leduc C, Joly E, Burt
A, Meddah B, Settaf A, Amason JT, Prentki M, Haddad PS (2008).
Antidiabetic activity of Nigella sativa seed extract in cultured
pancreatic cells, skeletal muscle, and adipocytes. Pharm. Biol., 46:
96-104.
Benhaddou AA, Martineau LC, Vallerand D, Haddad Y, Afshar A, Settaf
A, Haddad PS (2010). Multiple molecular targets underlie the
antidiabetic effect of Nigella sativa seed extract in skeletal muscle,
adipocyte and liver cells. Diabetes Obes. Metabol., 12: 148-157.
Bhatti AU, Berntorp K, Rehman FU (2009). Effect of prophetic medicine
Kalonji (Nigella sativa L.) on lipid profile of human beings, an in vivo

approach. W. Appl. Sci. J., 6: 1053-1057.

Bloch-Damti A, Bashan N (2005). Proposed mechanisms for the
induction of insulin resistance by oxidative stress. Antioxid. Redox
Signal, 7: 1553-1567.
Bonora E (2007). Antidiabetic medications in overweight/obese patients
with type 2 diabetes, drawbacks of current drugs and potential
advantages of incretin-based treatment on body weight. Int. J. Clin.
Pract, 61(Suppl. 154): 19-28.
Cameron NE, Cotter MA, Basso M, Hohman TC (1997). Comparison of
the effects of inhibitors of aldose reductase and sorbitol
dehydrogenase on neurovascular function, nerve conduction and
tissue polyol pathway metabolites in streptozotocin-diabetic rats.
Diabetol. 40: 271-281.
Datau EA, Wardhana, Surachmanto EE, Pandelaki K, Langi JA, Fias
(2010). Efficacy of Nigella sativa on serum free testosterone and
metabolic disturbances in central obese male. Acta Med. Indones.,
42: 130-134.
DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA,
Buchanan TA, Clement SC, Henry RR, Hodis HN, Kitabchi AE, Mack
WJ, Mudaliar S, Ratner RE, Williams K, Stentz FB, Musi N, Reaven
PD (2011). Pioglitazone for Diabetes Prevention in Impaired Glucose
Tolerance. N. Engl. J. Med., 364: 1104-1115.
Dinarello CA (2011). Blocking interleukin-1 in acute and chronic
autoinflammaotry diseases. J. Intern. Med., 269: 16-28.
Donath MY, Halban PA (2004). Decreased beta-cell mass in diabetes,
significance, mechanisms and therapeutic implications. Diabetol., 47:
581-589.
Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Perren A,
Ehses JA (2008). Islet Inammation in Type 2 Diabetes, From
metabolic stress to therapy. Diabetes Care, 31(Suppl. 2): S161
S164.
El-Dakhakhny M, Mady N, Lembert N, Ammon HP (2002). The
hypoglycemic effect of Nigella sativa oil is mediated by extra
pancreatic actions. Planta Med., 68: 465-466.
El-Kadi A, Kandil M (1987). The black seed (Nigella sativa) and
immunity, its effect on human T cell subset. Fed. Proc., 46: 12221228.
El-Zawahrawy M, Al-Zahrra S (1998). Effect of Nigella sativa on blood
level and structure of liver and pancreas in adult male albino rats. AlAzhar Med. J., 27: 479-483.
Fararh KM, Atoji Y, Shimizu Y, Shiina T, Nikami H, Takewaki T (2004).
Mechanisms of the hypoglycaemic and immunopotentiating effects of
Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Res.
Vet. Sci., 77: 123-129.
Fararh KM, Atoji Y, Shimizu Y, Takewaki T (2002). Isulinotropic
properties of Nigella sativa oil in Streptozotocin plus Nicotinamide
diabetic hamster. Res. Vet. Sci., 73: 279-282.
Grover JK, Yadav SP (2004). Pharmacological actions and potential
uses of Momordica charantia: A review. J. Ethnopharmacol., 93: 123132.
Hanafy MS, Hatem ME (1991). Studies on the antimicrobial activity of
Nigella sativa seed (black cumin). J. Ethnopharmacol., 34: 275-278.
Holberg MA, Hotamisligil GS (2006). Inflammation and metabolic
disorders. Nature, 444: 860-867.
Houstis N, Rosen ED, Lander ES (2006). Reactive oxygen species
have a causal role in multiple forms of insulin resistance. Nature, 440:
944-948.
Ilaiyaraja N and Khanum F (2010). Nigella sativa L, A review of
therapeutic applications. J. Herb. Med. Toxicol., 4: 1-8.
Jakobsen J, Lundbaek K (1976). Neuropathy in experimental diabetes,
an animal model. Br. Med. J., 2: 278-279.
Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP,
Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G (2006).
Glycemic durability of rosiglitazone, metformin, or glyburide
monotherapy. N. Engl. J. Med., 355: 2427-2443.
Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B (2006). Biochemical
effects of Nigella sativa L. seeds in diabetic rats. Indian J. Exp. Biol.,
44: 745-748.
Kanter M (2008). Effects of Nigella sativa and its Major Constituent,
Thymoquinone on Sciatic Nerves in Experimental Diabetic
Neuropathy. Neurochem. Res. 33: 87-96.
Kanter M, Akpolat M, Aktas C (2009). Protective effects of the volatile

Akash et al.

oil of Nigella sativa seeds on -cell damage in streptozotocin-induced

diabetic rats, a light and electron microscopic study. J. Mol. Hist., 40:
379385.
Kanter M, Coskun O, Budancamanak M (2005A). Hepatoprotective
effects of Nigella sativa L. and Urtica dioica L. on lipid peroxidation,
antioxidant enzyme systems and liver enzymes in carbon
tetrachloride-treated rats. W. J. Gastroenterol., 11: 66846688.
Kanter M, Coskun O, Korkmaz A, Oter S (2004). Effects of Nigella
sativa on oxidative stress and beta-cell damage in streptozotocininduced diabetic rats. Anat. Rec. A. Discov. Mol. Cell Evol. Biol., 279:
685691.
Kanter M, Coskun O, Uysal H (2006A). The antioxidative and
antihistaminic effect of Nigella sativa and its major constituent,
thymoquinone on ethanol-induced gastric mucosal damage. Arch.
Toxicol., 80: 217224.
Kanter M, Demir H, Karakaya C, Ozbek H (2005B). Gastroprotective
activity of Nigella sativa L oil and its constituent, thymoquinone
against acute alcohol-induced gastric mucosal injury in rats. W. J.
Gastroenterol., 11: 66626666.
Kanter M, Meral I, Yener Z, Ozbek H, Demir H (2003). Partial
regeneration/proliferation of the -cells in the islets of Langerhans by
Nigella sativa L. in streptozocin-induced diabetic rats. Tohoku J. Exp.
Med., 20: 213219.
Kanter M, O Coskun, M Kalayc, S Buyukbas, F Cagavi (2006B).
Neuroprotective effects of Nigella sativa on experimental spinal cord
injury in rats. Hum. Exp. Toxicol., 25: 127133.
Karachalias N, Babaei-Jadidi R, Ahmed N, Thornalley PJ (2003).
Accumulation of fructosyl-lysine and advanced glycation end
products in the kidney, retina and peripheral nerve of streptozotocininduced diabetic rats. Biochem. Soc. Trans., 31: 14231425.
Khader M, Eckl PM, Bresgen N (2007). Effects of aqueous extracts of
medicinal plants on MNNG-treated rat hepatocytes in primary
cultures. J. Ethanophormacol., 112: 199202.
Luo Y, Kirksaether N, Lager I, Umegaki H, Wang X, Abe R, Roth GS
(1998). Dopamine induces apoptosis through an oxidation-involved
SAPK/JNK activation pathway. J. Biol. Chem., 273: 37563764.
Maritim AC, Sanders RA, Watkins JB 3rd (2003). Oxidative stress and
antioxidants. A review. J. Biochem. Mol. Toxicol., 17: 2438.
McFarlane SI (2009). Antidiabetic medications and weight gain,
implications for the practicing physician. Curr. Diab. Rep., 9: 249
254.
Mitri J, Hamdy O (2009). Diabetes medications and body weight. Expert
Opin. Drug Saf., 8: 573584.
Mathur ML, Jyoti G, Ruchika S, Kripa RH (2011). Antidiabetic Properties
of a Spice Plant Nigella sativa. J. Endocrinol. Metab.,
Doi,10.4021/jem12e.
Otoom SA, Orn T, Al-Safi SA, Kerem ZK, Alkofahi A (2006). The use of
medicinal herbs by diabetic Jordanian patients. J. Herb.
Pharmacother., 6: 31-41.
Paarakh PM (2010). Nigella sativa Linn.- A comprehensive review.
Indian J. Nat. Prod. Resourc. 1: 409-429.

6889

Pari L, Sankaranarayanan C (2009). Benecial effects of thymoquinone

on hepatic key enzymes in streptozotocinnicotinamide induced
diabetic rats. Life Sci., 85: 830-834.
Prasad SK, Kulshreshtha A, Qureshi TN (2009). Antidiabetic activity of
some herbal plants in streptozotocin induced diabetic albino rats.
Pak. J. Nutr., 8: 551-557.
Purnell JQ, Weyer C (2003). Weight effect of current and experimental
drugs for diabetes mellitus, from promotion to alleviation of obesity.
Treat. Endocrinol., 2: 33-47.
Rahimi R, Nikfar S, Larijani B, Abdollahi M (2005). A review on the role
of antioxidants in the management of diabetes and its complications .
Biomed. Pharmacother., 59: 365-373.
Rchid H, Chevassus H, Nmila R, Guiral C, Petit P, Chokari M, Sauvaire
Y. (2004). Nigella sativa seed extracts enhance glucose-induced
insulin release from rat-isolated Langerhans islets. Fundam. Clin.
Pharmacol., 18: 525-529.
Sachdeva MM, Stoffers DA (2009). Mini-review, Meeting the Demand
for Insulin, Molecular Mechanisms of Adaptive Postnatal -Cell Mass
Expansion. Mol. Endocrinol., 23: 747-758.
Salem ML (2005). Immunomodulatory and therapeutic properties of the
Nigella sativa L. seed. Int. Immunopharmacol., 5: 1749-1770.
Sankaranarayanan C, Pari L (2011). Thymoquinone ameliorates
chemical induced oxidative stress and -cell damage in experimental
hyperglycemic
rats.
Chem.
Biol.
Interact.,
Doi,10.1016/j.cbi.2011.02.029.
Sayed M (1980). Traditional medicine in health care. J.
Ethnopharmacol., 2: 19-22.
Sharma AK, Thomas PK, De-Molina AF (1977). Peripheral nerve ber
size in experimental diabetes. Diabetes, 26: 689-692.
Song F, Jia W, Yao Y, Hu Y, Lei L, Lin J, Sun X, Liu L (2007). Oxidative
stress, antioxidant status and DNA damage in patients with impaired
glucose regulation and newly diagnosed Type 2 diabetes. Clin. Sci.
(Lond), 112: 599-606.
Tekeoglu I, Dogan A, Ediz L, Budancamanak M, Demirel A. (2007).
Effects of Thymoquinone (Volatile Oil of Black Cumin) on
Rheumatoid Arthritis in Rat Models. Phytother. Res., 21: 895-897.
Wellen KE, Hotamisligil GS (2005). Inflammation, stress, and diabetes.
J. Clin. Invest., 115: 1111-1209.
Wild S, Roglic G, Green A, Sicree R, King H (2004). Global prevalence
of diabetes, estimates for the year 2000 and projections for 2030.
Diabetes Care, 27: 1047-1053.
Yki-Jrvinen H (2004). Thiazolidinediones. N. Engl. J. Med., 351: 11061118.
Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar
M (2000). Diuretic and hypotensive effects of Nigella sativa in the
spontaneously hypertensive rat. Therapy, 55: 379-382.