Therapeutic Effect Of Nigella Sativa Oil On Different Clinical And Biochemical Parameters In Metabolic Syndrome

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1 ISPUB.COM The Internet Journal of Pharmacology Volume 5 Number 2 Therapeutic Effect Of Nigella Sativa Oil On Different Clinical And Biochemical Parameters In Metabolic A Najmi, S Haque, R Khan, M Nasiruddin Citation A Najmi, S Haque, R Khan, M Nasiruddin. Therapeutic Effect Of Nigella Sativa Oil On Different Clinical And Biochemical Parameters In Metabolic. The Internet Journal of Pharmacology Volume 5 Number 2. Abstract Introduction: The seeds of Nigella sativa plant have been used to promote health and fight disease for centuries especially in the Middle East and Southeast Asia. This plant has been a great focus of research. This clinical study was undertaken to know the adjuvant effect of Nigella sativa oil on various clinical and biochemical parameters of Insulin resistance syndrome. Methodology: This prospective randomized control study was conducted at the tertiary health care centre of north India. After final diagnosis and considering inclusion and exclusion criteria one hundred and sixty one patients were enrolled in this study. Informed and written consent was taken from all the patients enrolled. Approval from institutional ethical committee was taken. Patients were divided into two groups. In-group I (standard group) patients were advised atorvastatin 10 mg once a day, metformin 500 mg twice a day, atenolol 50 mg once a day, amlodipine 5 mg once a day for a period of six weeks. In group II (Nigella sativa) group, patients were advised the above standard medication plus Nigella sativa oil 2.5 twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. Result: The abovementioned methodology was followed and it was found that the difference of percentage improvement in group II was significant with reference to low density lipoprotein, high density lipoprotein and fasting blood glucose (p<.05). Conclusion: Nigella sativa oil was found to be effective as add on therapy in patients of insulin resistance syndrome. Nigella sativa oil has a significant activity in diabetic and dyslipidemic patients. INTRODUCTION The National Cholesterol Education Program's Adult Treatment Panel III report (ATP III) identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The etiology, prevention and treatment of the metabolic syndrome are currently the focus of intense research activities. As public health epidemics go, metabolic syndrome does not seem to pack the punch of more sharply defined health threats, such as lung cancer or heart disease. But statistics expose some harsh realities. According to a 2002 report from the centre for disease control and prevention, about 22% of United States adults have metabolic syndrome. Expert believe that the report, based on data collected between 1988 and 1994 underestimate the current number of persons who have metabolic syndrome. Alternative medicine has opened new door for the treatment of cardiometabolic disorders which has attained epidemic proportion throughout the world. Nigella sativa seed, used for centuries for medicinal and culinary purposes and reported to possess a number of pharmacological properties, including antioxidant, anti-inflammatory, hypoglycemic, antihypertensive and antihyperlipidemic properties 1. But no study had been done previously in patients of metabolic syndrome. Hence it was considered worthwhile to study the adjuvant effect of Nigella sativa oil on various clinical and biochemical parameters in patients of Metabolic. The seeds of Nigella sativa plant have been used to promote health and fight disease for centuries especially in the Middle East and Southeast Asia. In South Asia, it is called Kalonji, its Arabic name is Habat-ul-Sauda and its English 1 of 11

2 name is Black cumin..the plant is widely grown in different parts of the world and is an annual herb cultivated in India. As an oriental spice, Nigella sativa has long been used as a natural remedy for the treatment of many acute as well as chronic diseases. This plant has been a great focus of research and has several traditional uses and consequently has been extensively studied for its chemical constituents and biological activities. Figure 1 Figure 1: Seeds of Nigella sativa plant >88 cms for females 2. Serum triglyceride > 150 mg % 3. Serum HDL <50 mg % 4. Blood pressure > 140/90 mm Hg 5. Fasting blood sugar > 110 mg % To diagnose a patient as a case of metabolic syndrome at least 3 or > 3 criteria should be present. EXCLUSION CRITERIA Pregnancy Type I diabetes mellitus Acute coronary syndromes and cerebrovascular accidents 4. Impaired liver function test 5. Patients of chronic renal disease 6. Familial dyslipidemia Advices about dietary and lifestyle changes were given to both Nigella sativa and standard groups. Dietary advice as recommended by NCEP was given. Eat low fat, low cholesterol foods Use low fat cooking methods e.g. Use nonstick pans, barbeque, roast, boil. MATERIAL AND METHODS After final diagnosis and considering inclusion and exclusion criteria patients were enrolled in this prospective study. Ethical Issues: Approval from institutional ethical committee was taken. Informed and Written Consent: The participants were informed of all possible expected benefits and possible harm ensuing from the study. Written consent was obtained from the study subjects. Study Design: Randomized prospective controlled study INCLUSION CRITERIA: 1. Abdominal obesity: Waist circumference >102 cms for males 2 of 11 Avoid alcohol consumption. Eat more fruits, vegetables and whole grains. Exercise: Patients of both groups were advised to take a brisk 30 minutes walk for 5 days in a week on empty stomach or one hour after having a meal. Waist circumference measurement technique Place measuring tape, holding it parallel to floor, around abdomen at the level of the iliac crest. Hold tape snug but do not compress the skin. Measure circumference at the end of normal expiration. (Identification, evaluation and treatment of overweight and obesity in adults: the practical guide. Bethesda National Institute of Health 2000, NIH publication ).

3 Figure 2 Atorvastatin 10 mg once a day Figure 2: Waist circumference measurement technique (With courtesy from McGraw Hill companies, 2004) Metformin 500 mg twice a day Amlodipine 5 mg once a day Atenolol 50 mg once a day Aspirin 150 mg once a day STATISTICAL ANALYSIS Pre and post treatment mean ± standard deviation of each parameter was calculated for both groups. The data were analyzed statistically using unpaired t test between Group I (Standard) and Group II (Nigella sativa).all the statistic were done by using 13 th version of SPSS software. OBSERVATIONS AND RESULTS Specific investigations: Blood sugar both fasting and postprandial Renal function test Fasting lipid profile Urine for albumin Liver function tests Nigella sativa Oil Nigella sativa oil (Kalonji oil, Mohammedia products, Red Hills, Nampally, Hyderabad) was procured from local market at Aligarh. As per manufacturer's information, it was prepared by steam distillation at Hyderabad, A.P., and India STUDY GROUPS: Group I. (Standard): Patients who were kept on standard regimen Group II.(Nigella sativa): Patients who were kept on standard regimen plus Nigella sativa oil 2.5 ml twice daily per orally for a period of six weeks as an add on therapy Standard Treatment: Following drugs were prescribed as a standard treatment for various disorders. 3 of 11 The present study was conducted on newly detected patients of metabolic syndrome in J.N. Medical College A.M.U. Aligarh from October 2005 to March 2007.The study group comprised of 161 patients. There were 115 males and 46 females. The age group of the patients varied from 20 years to 70 years but majority of the patients were in years age group. These patients were diagnosed as having metabolic syndrome according to ATP III criteria. Distribution of patients according to parameters of ATP III definition: Maximum numbers of our patients were suffering from obesity (93.7 %%) followed by low serum HDL (87.5 %) followed by raised serum triglyceride (84.3 %) followed by fasting blood glucose > 110 mg % (63.7 %) followed by hypertension (62.5 %)

4 Figure 3 Figure 5 TABLE: Distribution of patients according to parameters of ATP III definition TABLE 1: Body mass index Figure 4 GRAPH 3. Distribution of metabolic syndrome patients according to ATP III criteria Abdominal circumference: According to ATP III criteria abdominal obesity is calculated by measuring waist circumference. The cut off points for males and females are > 102 cms and > 88 cms respectively. The presence of abdominal obesity is more highly correlated with the metabolic risk factors than is an elevated BMI. Abdominal girth was reduced in both the groups. More reduction was seen in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of abdominal circumference are listed in the following table. Figure 6 TABLE 2: Abdominal circumference Hip circumference: Hip circumference was reduced in both the groups. More reduction was seen in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of hip circumference are listed in the following table. Figure 7 TABLE 3. Hip circumference DIFFERENT CLINICAL AND BIOCHEMICAL PARAMETERS Body mass index (BMI): According to WHO clinical criteria for metabolic syndrome the cut off point for BMI is > 30 Kg / meter 2. There was improvement in BMI of both the groups.improvement was more in Nigella sativa group as compared to Standard group but the difference in improvement between two groups was not significant.mean ± S.D. of pre and post treatment values of BMI are listed in the following table. 4 of 11 Body weight: Body weights were reduced in both the groups. The improvement was more in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of body weight are listed in the following table.

5 Figure 8 Figure 11 TABLE 4: Body weight TABLE 7: Diastolic blood pressure Waist hip ratio: According to WHO criteria of metabolic syndrome, the cut off point of waist hip ratio for males and females are respectively > 0.9 and >0.85 respectively. Waist hip ratio was improved in both the groups. Improvement was more in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of waist hip ratio are listed in the following table. Blood glucose: According to ATP III criteria the cut off point for fasting blood glucose is > 110 mg %. Cut points for several of these are less stringent than usually required to identify a categorical risk factor because multiple marginal risk factors can impart significantly increased risk for cardiovascular disease. Fasting blood glucose was reduced in both the groups but the reduction was significantly more (P value <.05) in Nigella sativa group. Postprandial blood glucose was reduced in both the groups. There was more improvement in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of fasting blood glucose are listed in the following table Figure 9 TABLE 5: Waist hip ratio Figure 12 TABLE 8: Fasting blood glucose Blood pressure: According to ATP III criteria for metabolic syndrome the cut off limit of blood pressure is > 130 /85 but in our study we had taken inclusion criteria of > 140 / 90 mm Hg because of convenience. Both systolic and diastolic blood pressure was reduced in both the groups. There was more reduction in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of systolic blood pressure are listed in the following table. Figure 13 TABLE 9: Postprandial blood glucose Figure 10 TABLE 6: Systolic blood pressure Total cholesterol (TC): Total cholesterol was reduced in both the groups. Reduction was more in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of TC are listed in the following table. 5 of 11

6 Figure 14 Figure 17 TABLE 10: Total cholesterol Table 13: LDL Triglyceride (TG): According to ATP III criteria dyslipidemia was defined as TG > 150 mg %. Triglyceride was reduced in both the groups. Reduction was more in Nigella sativa group but the difference between two groups was not significant. Mean ± S.D. of pre and post treatment values of TG are listed in the following table. Table below showing Post treatment mean ± S. D of standard and Nigella sativa group, t values and P values Figure 18 Table 14: Group statistics: Independent sample t test Figure 15 TABLE 11: Triglyceride High density lipoprotein (HDL): According to ATP III criteria the cut off point for HDL is < 40 mg % for males and < 50 mg % for females but in our study we had taken single cut off point of < 50 mg % both for males and females because of the purpose of convenience and feasibility. HDL was increased in both the above groups. Improvement in HDL was significant in Nigella sativa group (P<.05) as compared to standard group. Mean ± S.D. of pre and post treatment values of HDL are listed in the following table. Figure 16 Table 12: HDL Low density lipoprotein (LDL): According to ATP III guidelines dyslipidemia was defined as LDL > 130 mg %. LDL was reduced in both the groups but the reduction was significantly more (P<.05) in Nigella sativa group as compared to standard group. Mean ± S.D. of pre and post treatment values of LDL are listed in the following table. Number of patients in Group I = 82 Number of patients in Group II = 79 P value <.05 is taken as significant 6 of 11

7 DISCUSSION In our study we had taken five parameters for the measurement of obesity. They were body mass index, waist circumference, hip circumference, body weight and waist hip ratio. Advices about dietary and lifestyle changes as recommended by National Cholesterol Education Programme were given to both Nigella sativa and standard groups. In addition Nigella sativa oil 2.5 ml twice daily was added as add on therapy in Nigella sativa group. There was improvement in all the five abovementioned parameters in both groups but the improvement was more in Nigella sativa group as compared to standard group. Obesity is a major risk factor for type 2 diabetes and cardiovascular disease. It also is an important component of metabolic syndrome, although in a minority of obese persons, insulin resistance does not develop. Insulin resistance may also develop in persons classified as lean by body mass index (BMI) standards, who could thus be considered metabolically obese. Visceral adipose tissue has been proposed as the major site of fat deposition associated with the metabolic consequences of obesity 2. It is thought that visceral, or central, adiposity is the initial physical event that results in insulin resistance, by an increase in free fatty acid flux in portal and systemic circulations. No such clinical study had been done previously on antiobesity activity of Nigella sativa.antiobesity activity of Nigella sativa is being reported for the first time by us. The exact mechanism regarding antiobesity action is not known. In an animal study on rats 3 showed that petroleum ether extract of Nigella sativa had slight anorexic effect.the various constituents of Nigella sativa seeds for example lipase 4 may be responsible for its antiobesity action. It is the android obesity or apple shaped obesity that is associated with metabolic syndrome. The distribution of body fat is more important than the total quantity of fat in predicting the diabetes mellitus and associated macro vascular disease. The measurement of central obesity can be done by (1) measuring waist hip ratio, desired ratio, women < 0.8, men < 0.9 (2) measurement of waist: more than 88 cms in women and more than 102 cms in men, places them in high risk category for the development of metabolic syndrome. (ATP III guidelines 2001). Waist circumference has very crucial role in the detection and diagnosis of metabolic syndrome. Overweight and obesity are associated with insulin resistance and the metabolic syndrome. However, the presence of abdominal obesity is more highly correlated with the metabolic risk factors than is an elevated BMI. Therefore, the simple 7 of 11 measure of waist circumference is recommended to identify the body weight component of the metabolic syndrome. In our study for the treatment of hypertension we advised atenolol 50 mg plus amlodipine 5 mg in standard group.in Nigella sativa group we added Nigella sativa oil 2.5 ml twice daily. Reduction in both systolic and diastolic blood pressure was more in Nigella sativa group as compared to standard group. Our results were the same as reported previously in various studies. The various mechanism that were proposed for its antihypertensive effect of Nigella sativa were centrally acting antihypertensive agent, 5 calcium channel blocking activity 6 and its diuretic activity. 7 The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provides guidelines for intensive treatment of hypertension. Although use of thiazide diuretics and betablockers has been avoided in patients with glucose tolerance abnormalities, the safety and efficacy of such medications have been demonstrated in large clinical trials Drugs of these classes can be used in treatment of hypertension in patients with metabolic syndrome. We had taken a combination of atenolol and amlodipine because of certain advantages. Although Joint National Committee six (JNC VII) emphasize on single drug therapy, in practice a large majority of hypertensive ultimately require two or more drugs. In the Hypertension Optimal Treatment (HOT) study, a multicenter trial conducted in 26 countries, 70 % patients who achieved target blood pressure (BP) were being treated with two drugs. Even initial treatment of mild to moderate hypertension with a low dose combination is being advocated as an alternative strategy. Since BP is kept up by several interrelated factors, an attempt to block one of them tends to increase compensatory activity of the others. It is rational in such cases to combine drugs with different mechanism of actions for example drugs which increase plasma rennin activity diuretics, calcium channel blockers, Angiotensin converting enzyme inhibitors may be combined with drugs which lower plasma rennin activity beta blockers, clonidine, methyldopa. Atenolol is cardioselective beta one antagonist. Because of longer duration of action once daily dose is often sufficient. Side effects related to central nervous system action are less likely. No deleterious effect on lipid profile has been noted. Amlodipine is calcium channel blocker of dihydropyridine (DHP) group. It has complete but slow oral absorption. The early vasodilator side effects like palpitation, flushing, and postural dizziness are largely avoided. Diurnal fluctuation in blood level is small

8 and actions extend over the next morning. Its bioavailability is higher and more consistent. cholesterol 12. Further research is necessary to identify the mode of action of black cumin seeds. In our study for the treatment of elevated blood glucose we advised metformin 500 mg twice daily in standard group. In Nigella sativa group we added Nigella sativa oil 2.5 ml twice daily. Reduction in fasting and postprandial blood sugar in Nigella sativa group was more as compared to standard group. This reduction was statistically significant (P value < 0.05) in case of fasting blood glucose but not significant in case of postprandial blood glucose. We had taken metformin because of certain advantages. Metformin is a biguanide agent that lowers blood glucose primarily by decreasing hepatic glucose output and reducing insulin resistance. When used as monotherapy, metformin does not cause hypoglycemia and is thus termed an antihyperglycemic. The reported incidence of lactic acidosis during metformin treatment is less than 0.1 cases per thousand patient years and the mortality risk is even lower. Metformin does not promote weight gain and can reduce plasma triglyceride by 15 % to 20 %.Metformin is the only therapeutic agent that has been demonstrated to reduce macrovascular events in type 2 diabetes mellitus.(u.k. Prospective Diabetes Study Group, 1998). The Diabetes Prevention Program demonstrated the effectiveness of lifestyle change in persons with impaired fasting glucose, but metformin hydrochloride was also effective in delaying progression to overt diabetes in patients with impaired fasting glucose. 8 The same results were reported previously in various animal models of diabetes. The various mechanism proposed for its hypoglycemic activity were insulin sensitizing action 3 and stimulatory effect on beta cell function 9 Increase in High density lipoprotein (HDL) was more in Nigella sativa group as compared to standard group. This difference was significant (P value < 0.05). The same result was also reported previously 13 in rats. Reduction in Low density lipoprotein (LDL) cholesterol was significantly more (P value < 0.05) in Nigella sativa group as compared to standard group. LDL-c level may be decreased by increasing the production of LDL-c receptors. 14 Improvement in triglyceride (TG) was more in Nigella sativa group as compared to standard group but this difference was not significant. The same results were reported previously.treatment of the dyslipidemia of metabolic syndrome should involve nonpharmacologic interventions, including weight loss, exercise, and a low-fat diet. Reducing LDL-C levels with use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) is also appropriate for patients with metabolic syndrome. The ATP III guidelines recommend that LDL-C be the primary target of lipid-lowering therapy when a patient's triglyceride level is below 500 mg/dl. We had take atorvastatin because of certain advantages.statins are competitive inhibitors of 3hydroxy-3-methyl glutaryl coenzyme A (HMG Co A) reductase, which catalyzes an early, rate limiting step in cholesterol biosynthesis. The statins are the most effective and best tolerated agents for treating dyslipidemia (Goodman and Gilman's The pharmacological basis of therapeutics ) Statins have certain other cardioprotective benefits besides LDL lowering like improvement in endothelial function, 15 plaque stabilization 16, decreased the risk of coronary heart disease and levels of C- reactive proteins 17, inhibiting lipoprotein oxidation both in vivo and ex vivo 18, reduce platelet aggregation. Atorvastatin as a single agent may obviate the need for multiple drug therapy in high-risk patients 19. Atorvastatin is relatively more potent, cost effective and got the highest LDL cholesterol lowering efficacy at maximal daily dose of 80 mg.hepatic cholesterol synthesis is maximal between midnight and 2:00 A.M. Thus statins with half life of 4 hours or less (all but atorvastatin and rosuvastatin) should be taken in the evening or bed time. Atorvastatin has a long half life (18-24 hours), which allows administration of this statin at any time of the day. In our study for the treatment of dyslipidemia, we advised atorvastatin 10 mg once a day in standard group. In Nigella sativa group we added Nigella sativa oil 2.5 ml twice daily. Reduction in total cholesterol was more in Nigella sativa group (NS) as compared to standard group. Our results were the same as reported previously in various studies. Previous research workers 10 also reported the cholesterol lowering effect of Nigella sativa oil in animal studies. The presence of various unsaturated fatty acids like Arachidonic, eicosadienoic, linoleic, linolenic, oleic and almitoleic acid 11 may be responsible for the improvement of lipid profile. The various mechanisms were proposed for the lowering of cholesterol. The seeds may either inhibit de novo cholesterol synthesis or stimulate bile acid excretion. It is well-known that both effects would lead to a decrease in serum 8 of 11 In our study we advised low dose aspirin to the patients of both standard and Nigella sativa group. People with the

9 metabolic syndrome typically manifest elevations of fibrinogen, plasminogen activator inhibitor-1, and other coagulation factors. These abnormalities, however, are not routinely detected in clinical practice. For primary prevention, the only available long-term approach to counter their contribution to arterial thrombosis is low-dose aspirin or other antiplatelet agents. These agents, especially aspirin, are recommended in patients with established atherosclerotic cardiovascular disease (ASCVD) provided they are not contraindicated. Their efficacy in individuals with type 2 diabetes mellitus without ASCVD has not been established conclusively through clinical trials, although they are widely recommended in such individuals. In metabolic syndrome patients who are at moderately high risk for ASCVD events, aspirin prophylaxis is an attractive therapeutic option to lower vascular events. 20 CONCLUSION Among the five parameters for the ATP III definition of metabolic syndrome, significant beneficial effect of adding Nigella sativa oil was seen in case of high density lipoprotein followed by fasting blood glucose. Other parameters (blood pressure, serum triglyceride and waist circumference) were also improved in both the standard and Nigella sativa group. This improvement was more in Nigella sativa group as compared to standard group but this was not statistically significant. There was improvement in all the clinical and biochemical parameters in both the standard and Nigella sativa group. The different clinical parameters were systolic and diastolic blood pressure, body mass index, body weight, waist circumference, hip circumference and waist hip ratio. The various biochemical parameters were fasting and postprandial blood glucose, triglyceride, total cholesterol, high density lipoprotein, low density lipoprotein. Improvement was more in Nigella sativa group as compared to standard group for all the parameters. The improvement was statistically significant in case of fasting blood glucose, low density lipoprotein and high density lipoprotein. Our results are in conformity with earlier reports. However to the best of our knowledge antiobesity activity of Nigella sativa oil is being reported for the first time by us. The most important action of Nigella sativa that may be responsible for its beneficial effect in metabolic syndrome is its insulin sensitizing action. The various components of Nigella sativa that may be responsible for its beneficial effects in insulin resistance syndrome are thymoquinone, thymol, various unsaturated fatty acids, lipase and tannins. 9 of 11 Acknowledgements: The author is grateful to Dr.Mohd. Tariq Salman for his expert statistical guidance. The authors would also like to thanks Dr. Razi Ahmad and Dr.Kamal C.M for their guidance and support. References 1. Bamosa AO et al (1997): Effect of oral ingestion of Nigella sativa seeds in some blood parameters. Saudi Pharm J, 5(2-3): Wajchenberg BL Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome.endocr Rev 2000; 21(6): Abdellatif Settaf, Aziz Elimadi, Yehiya Cherrah, et al, The petroleum ether extracts of Nigella sativa seeds exert insulin sensitizing and lipid lowering action in rats.journal.of Ethanopharmacology, 2004, Volume 94, Issue 2-3: Aylin Akova, Gulem Ustun, Activity and adsorption of lipase from Nigella sativa seeds, Biotechnology Letters, Volume 22, Page , Tahir KE, Ashour M. M. S., et al. (1993). The respiratory effects of the volatile oil of the Black Seed (Nigella sativa) in guinea pigs: Elucidation of the mechanism(s) of action. General Pharmacology 24(5): : Dep. Pharmacol., College Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. 6. Aqel, M. (1992a) The calcium antagonistic effect of the volatile oil of Nigella sativa seeds. Dirasat Series B Pure and Applied Sciences 19(1): Dep. Anat., Fac. Med., Anat. /Smooth Muscles, Univ. Aiwa, USA. 7. Zaoui, A., Cherrah, Y. et al. (2000). Diuretic and hypotensive effects of Nigella sativa on the spontaneously hypertensive rat. Therapie London. Mai Juin 55(3): : Laboratoire de Pharmacologie et Toxicologie, Faculte de Medecine et Pharmacie de Rabat, Universite Med V, Rabat, Morocco. 8. Knowler WC, Barrett Connor E, Fowler SE et al.reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.diabetes Prevention Programe Research group N Eng J Med 2002, 346(6): Meral, I., Z. Yener, T. Kahraman and N. Mert, Effect of Nigella sativa on glucose concentration, lipid peroxidation, anti-oxidant defense system and liver damage in experimentally-induced diabetic rabbits. J. Vet. Med. A. Physiol. Pathol. Clin. Med., 48: ). 10. Abdul Sattar, Allah Ditta, Muhammad Tayyib, Muhammad Ashraf.Estimation of serum lipids in albino Rats fed on palm oil and atherogenic diet and Nigella sativa. Pakistan Postgrad Med J Sep 2003; 14(3): El-Dakhakhny M (1963): Studies on chemical constitution of Egyptian N sativa L seeds II. The Essential oil. Planta Med, 11; Beynen, A.C., M.B. Katan and L.F.M. Van Zutphen, Hypo- and hyperresponders: individual differences in the response of serum cholesterol concentration to changes in diet. Adv.Lipid Res., 22: Amir Hamzo Dahri, Atta Muhammad Chandiol, Ali Akbar Rahoo Rafique Ahmed Memon, Effect of Nigella sativa on serum cholesterol of albino rats, (2001) Department of Pathology, Biochemistry and Medicine Peoples Medical College Nawabshah. 14. 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11 Author Information Ahmad Najmi, MBBS, MD Junior Resident III, Dept. Of Pharmacology, J.N.Medical College, Aligarh Muslim University Shahzad F. Haque, MBBS, MD Reader, Dept. Of Medicine, J.N.Medical College, Aligarh Muslim University Rahat Ali Khan, MBBS, MD Professor, Dept. Of Pharmacology, J.N.Medical College, Aligarh Muslim University Mohd Nasiruddin, MBBS, MD Lecturer, Dept. Of Pharmacology, J.N.Medical College, Aligarh Muslim University 11 of 11