The Effects of Short-Term Administration of Weight Reducing Herbal Drug (Mehzileen) on Serum Enzymes in Common Rabbits.
Abstract: In the present study the weight reducing herbal drug, Mehzileen administered orally to common rabbits Oryctolagus cuniculus in a daily dose of 20 mg/ Kg body weight for 27 days. Blood samples drawn on day 0, 3, 7, 10 and 27 respectively were used to measure serum enzymes Aspartate Amino Transferase (AST) and Alanine Amino Transferase (ALT).Both the enzymes showed reduction in the early period of drug administration then started to elevate from day 10 of treatment. However AST remained significantly lower (p less than 0.05) in test animals, while ALT continued to rise with slightly lower levels than initial concentrations at the end of experiment. These alterations in the AST and ALT levels suggest that major ingredients of the herbal drug used, probably interfere the metabolic activities of liver parenchyma and hepatocytes respectively.
Keywords: Herbal drugs, obesity, liver enzymes, weight reduction
Obesity is a condition where the natural energy reserves, stored in fatty tissues of human and animals are elevated to impair the health. Excess energy input occurs only during the developing phase of obesity . It is a serious illness that can lead to many medical complications like high blood pressure, diabetes, abnormal blood fats, coronary artery disease, stroke, osteoarthritis, sleep apnea, cancer, fatty liver disease, gallbladder disease and gout [2-4].
The non-pharmacologic approaches for weight reduction include diet, exercise and behavioral treatment. Many studies demonstrate that obese adults can lose weight about 0.5 kg per week by decreasing their daily intake to 500 to 1000 k cal. below the caloric intake, required for the maintenance of their current weight . Severe caloric restriction increases the rapidity of weight loss, but not the rate of long-term success in maintaining a reduced weight . In addition to caloric restriction, exercise is most likely to promote the long-term maintenance of reduced weight [7-9]. Persons who combine caloric restriction and exercise with behavioral treatment may expect to lose about 5 to 10 percent of pre- intervention body weight over a period of four to six months [5, 10, 11].
Drug therapy is a pharmacologic approach for the treatment of obesity and to treat obesity, medications were proposed as short-term adjuncts for patients who reach "ideal body weight", and maintain a reduced weight indefinitely.
Such short-term approaches proved unsuccessful .
Nowadays many herbs are being used for the treatments of obesity and weight loss is found evident in people using herbal products [13-16]. Research has suggested that cayenne pepper in the diet may help people to lose weight [17-20]. Green tea may support in a weight loss program by increasing energy expenditure or by inhibiting the digestion of fat in the intestine [21-23]. The ability of yohimbine to stimulate the nervous system  and promote the release of fat from fat cell, has led to claim that it might help weight loss by increasing metabolic rate, reducing appetite or increase fat burning [25, 26]. The herb guarana contains caffeine, which elevates the metabolic rate and has stimulatory effect on central nervous system .
Presently many herbal drugs of different combinations are commercially available, claiming their immediate efficacy in the management of obesity without any side effects. Although these products may successfully reduce, the body weight but the sufficient data on their side effects of the interactions of their ingredients are not available.
The objective of this study is to investigate the adverse effects of weight reducing herbal drug, MEHZILEEN on liver of common rabbits Oryctolagus cuniculus by measuring the changes in serum enzymes Aspartate Amino Transferase (AST) and Alanine Amino Transferase (ALT).
The herbal weight reducing drug MEHZILEEN (Azeemi laboratories, Karachi) used in this study has ingredients; Ajwain (Ptychotis ajowan), Caraway (Carum carvi), Fennel (Foeniculum vulgare mill), Fennel flower (Nigella sativa), Mugwort (Artemisia vulgaris), Pennyroyal (Mentha pulegium), Rue (Ruta graveolens) and Worm wood (Artemisia absinthium). All of these ingredients are medicinally important due to their physiological effects, specially on digestive system as well as for the treatment of obesity [28-35].
MATERIALS AND METHODS Animals
Eight rabbits (Oryctolagus cuniculus) used in this experiment, 12 months old, ranging from 1500-1550 g, purchased from local supplier. They kept in well- ventilated barred cages, placed in the departmental animal house. Clean, healthy and controlled conditions (temperature 35+- 3 C@) at 12 hour day/ night cycle were maintained throughout the experiment. Animals fed ad libitum with their normal diet including alfalfa grass, cabbage, carrots and cucumber alternately for about one month prior to the start of experiment. Later they divided equally in control and test groups for comparative study.
The selected weight reducing herbal drug MEHZILEEN (Azeemi Laboratories, Karachi) available in tablet form, was purchased from a local chemist. Each tablet of 375 mg recommended for obese or overweight persons in a dose of 2 tablets morning and evening for 4 - 6 weeks. The calculated daily oral dose for experimental animals was 20 mg/ Kg body weight. The drug was given orally daily to each test animal for approximately 4 weeks.
To find out the changes in the selected parameter after administration of drug, blood samples drawn on day 0, 3, 7, 10 and 27 respectively by 3cc disposable syringes from the marginal vein of ears of each rabbit. In order to obtain serum, the whole blood samples allowed to coagulate at room temperature for 1 hour and after centrifugation, supernatant was collected in eppendorf tubes to be refrigerated at 4oC.
In serum the enzymes AST and ALT were measured according to the method of Reitman et al.,  using commercially available biochemical kits (Randox, Cat. No. AS147,AL146) on day 0, 3, 7, 10 and 27. Absorbances were read on spectrophotometer. The data was analyzed statistically by t-test and two- way ANOVA.
The mean serum AST level in control rabbits remained almost constant i.e. in between 26.0 +- 0.55 IU/ l to 25.0 +- 0.57 IU/ l from day 0 to day 27. On the other hand test animals with mean AST level of 29.0 +- 0.53 IU/ l on day 0, showed a rapid fall from day 3 to day 10 (Figure 1a) with mean AST concentration of 7.0 +- 0.01 IU/ l in tests. From day 10 onwards, after the administration of drug, AST levels tend to rise but did not attain the initial concentration. The fall of AST concentration and then rise to lower than normal levels in test animals is significantly (p less than 0.05) depending on the duration of drug administered.
The significant reduction (p less than 0.05) in mean ALT concentration from 24.47 +- 0.38 IU/ l to 4.95 +- 0.70 IU/ l was observed in test rabbits from day 0 to day 10. While control rabbits showed a fall of 1.0 +- 0.07 IU/ l i.e. from 25.0 +- 0.58 IU/ l to 24.0 +- 0.51 IU/ l during this period. Following the administration of drug, from day
10 onwards mean ALT concentration in test animals began to rise towards the initial levels (Figure 1b) and the mean ALT concentration in test rabbits were 21.53 +- 0.38 IU/ l on day 27.
The weight loss can be achieved by the use of medications or herbs, which either decrease the appetite or involving digestive system by inhibiting the absorption from the intestine [37, 38].
However, herbal weight reducing drugs are not completely safe and free of adverse side effects as the cases of liver injury  and acute hepatitis associated with herbal dietary supplement for weight loss have been reported .
AST and ALT levels are reliable indicators of liver function as both enzymes are present in relatively higher concentrations in liver parenchymal cells and hepatocytes respectively. After the damage of cells, enzymes leak out into the blood . Any medication can alter liver enzyme levels  such as low levels of AST or higher levels of ALT caused by herbs and natural products.
In the present study, the significant lower levels of serum AST and ALT on day 10 after the administration of drug, suggest the effects of ingredients of herbal drug involving liver . These observations are supported by a study on Ruta graveolens toxicosis in goats, indicating the pathologic changes in various organs in addition to abnormal alterations in serum AST, cholesterol, the concentration of tissue calcium and phosphorus .
As the experiment was run for short duration, the gradual rise in ALT concentration would be significant if treatment continued for longer period, possibly damaging hepotocytes.
So far, there are little evidences that any of the available weight loss products would be effective, unless extra calories utilized by regular exercise and energy restriction by dietary modification. Further, the herbal drugs should be use by the consultancy of a person with sound knowledge of herbs and their side effects.
We gratefully acknowledge the financial grant awarded by the Dean, Faculty of Science, University of Karachi for this study.
 Guyton AC, Hall JE. Dietary Balances: Regulation of feeding; obesity and starvation; vitamins and minerals. In: Textbook of medical physiology. 11th ed. U.S.A.: W.B. Saunders Co 2006; p.893- 4.
 Bray GA, Macdiarmid J.The epidemic of obesity. West J Med 2000; 172(2): 78-1. http://dx.doi.org/10.1136/ewjm.172.2.78
 Despres JP. Intra-abdominal obesity: an untreated risk factor for type 2 diabetes and cardiovascular disease. J Endocrinol Invest 2006; 29 (3): 77-5.
 Schiel R, Beltschikow W, Kramer G, Stein G. Overweight, obesity and elevated blood pressure in children and adolescents. Eur J Med Res 2006; 11(3): 97-4.
 Wadden TA, Foster GD. Behavioral treatment of obesity. Med Clin North Am 2000; 84: 441- 20. http://dx.doi.org/10.1016/S0025-7125(05)70230-3
 Harvey BJ. Calorie restriction is more effective for obesity treatment than dietary fat restriction. Ann Behav Med 1999; 21(1): 35-4. http://dx.doi.org/10.1007/BF02895031
 Geliebter A, Maher MM, Gerace L. Effects of strength or aerobic training on body composition, resting metabolic rate, and peak oxygen consumption in obese dieting subjects. Am J Clin Nutr 1997; 66: 557-6.
 Mc Guire MT, Wing RR, Klem ML, Hill JO. Behavioral strategies of individuals who have maintained long-term weight losses. Obes Res 1999; 7: 334-7.
 Annesi JJ, Gojrala S. Relationship of exercise program participation with weight loss in adults with severe obesity: assessing psychologically based mediators. South Med J. 2010; 103 (11): 1119-4. http://dx.doi.org/10.1097/SMJ.0b013e3181f6d3d4
 Barabaz M, Spiegel D. Hypnotizability and weight loss in obese subjects. Int J Eat Disord 1989; 8: 335-6. http://dx.doi.org/10.1002/1098-108X(198905)8:3 less than 335::AID- EAT2260080309 greater than 3.0.CO;2-O
 Poston WSC, Hyder ML, O'Byrne KK, Foreyt JP. Where do diets, exercise, and behavior modification fit in the treatment of obesity? Endocrinol 2000; 13(2): 187-3.
 Bray GA, Greenway FL. Current and potential drugs for the treatment of obesity. Endocrinol Rev 1990; 20: 805-70. http://dx.doi.org/10.1210/er.20.6.805
 Moro CO, Basile G. Obesity and medicinal plants. Fitterapia 2000; 71(1): 73-9. http://dx.doi.org/10.1016/S0367-326X(00)00177-5
 Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL. An herbal supplement containing Ma Huang- Guarana for weight loss: a randomized, double- blind trial. Int J Obes Relat Metab Disord 2001; 25: 316-8. http://dx.doi.org/10.1038/sj.ijo.0801539
 Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA et al., Herbal ephedra/ caffeine for weight loss: a 6- month randomized safety and efficacy trial. Int J Obes Relat Metab Disord 2002; 26: 593-11. http://dx.doi.org/10.1038/sj.ijo.0802023
 Feng Y, Huang SL, Dou W, Zhang S, Chen JH, Shen Y, et al., Emodin, a natural product, selectively inhibits 11 beta- hydroxysteroid dehydrogenase type I and ameliorates metabolic disorder in diet - induced obese mice. Br J Pharmacol 2010; 161(1): 113-26. http://dx.doi.org/10.1111/j.1476-5381.2010.00826.x
 Yoshioka M, Docent E, Drapeau V. Combined effects of red pepper and caffeine consumption on 24 hr energy balance in subjects given free access to foods. Br J Nutr 2001; 85: 203- 8. http://dx.doi.org/10.1079/BJN2000224
 Yoshioka M, St-Pierre S, Drapeau V. Effects of red pepper on appetite and energy intake. Br J Nutr 1999; 82: 115-8.
 Sharpe PA, Granner ML, Conway JM, Ainsworth BE, Dobre M.Availability of weight -loss supplements: Results of an audit of retail outlets in a southeastern city.J Am Diet Assoc 2006; 106 (12): 2045-6. http://dx.doi.org/10.1016/j.jada.2006.09.014
 Powell SC. Red pepper as a probe for obesity. J Proteome Res 2010; 9(6): 2797-3.
 Dullo AG, Seydoux, J, Girardier L. Green tea and thrombogenesis: interaction between catechin polyphenol, caffeine and sympathetic activity. Int J Obes Relat Metab Disord 2000; 24: 252- 6. http://dx.doi.org/10.1038/sj.ijo.0801101
 Juhel C, Armand M, Pafumi Y.Greentea extract (AR25) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro.J Nutr Biochem 2000; 11: 45-6. http://dx.doi.org/10.1016/S0955-2863(99)00070-4
 Basu A, Sanchez K, Leyva MJ, Wu M, Betts NM, Aston CE, et al., Green tea supplementation affects body weight, lipids and lipid peroxidation in obese subjects with metabolic syndrome. J Am Coll Nutr 2010; 29(1): 31-9.
 Goldberg MR, Robertson D. Yohimbine: a pharmacological probe for the study of alpha 2-adrenoceptors. Pharmacol Rev 1983; 35: 143-37.
 Zahorska MB, Kucio C, Piskorska D. Adrenergic control of lipolysis and metabolic responses in obesity. Horm Metab Res 1986; 18: 693-4. http://dx.doi.org/10.1055/s-2007-1012409
 Kucio C, Jonderko K, Piskorska D.Does yohimbine act as a slimming drug? Isr J Med Sci 1991; 27: 550-6.
 Leung A, Foster S. Encyclopedia of Common Natural Ingredients used in Food, Drugs and Cosmetics. 2nd ed. New York: Johan Wiley and Sons 1996; p. 293-94.
 Greive M. A Modern Herbal. 2nd ed Leyal CF editor. New York: Dovers Publicaitons Inc 1971.
 Chevallier A. The Encyclopedia of Medicinal plants. London: Dorling Kindersley; 1996.
 Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17(4): 299- 6. http://dx.doi.org/10.1002/ptr.1309
 Birkner B, Gundling PW, Neuberger HO, Popp- Nowak W, Bettermann O, Kuchlbauer K. Fennel tea and damp warm compresses. Prescriptions for the stomach and intestine. MMW Fortschr Med 2004; 146(8): 12-3.
 Vaughan JG, Judd PA. The oxford book of healthy foods.U.S.A: Oxford University Press; 2006.
 Birdane FM, Cemek M, Birdane YO. Gulcin I, Buyukokuroglu ME. Beneficial effects of Foeniculum vulgare on ethanol- induced acute gastric mucosal injury in rats. World J Gasteroenterol 2007; 13(4): 607-11.
 Amin KA, Nagy MA. Effect of carnitine and herbal mixture extract on obesity induced by high fat diet in rats. Diabetol Metab Syndrome 2009; 1: 1-17.
 Kaur GJ, Arora DS. Bioactive potential of Anethum graveolens, Foeniculum vulgare and Trachyspermum ammi belonging to the family umbelliferae- current status. J Med Plant Res 2010; 4(2): 87-7.
 Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxaloacetic glutamic pyruvic transaminases. Am J Clin Path 1957; 28: 56-9.
 Allison DB, Fontaine KR, Heshka S, Mentore JL, Heymsfeild SB. Alternative treatment for weight loss: A critical review. Food Sci Nutr 2001; 41(1): 1-28. http://dx.doi.org/10.1080/20014091091661
 Tian WX, Li LC, Wu XD, Chen CC. Weight Reduction by Chinese medicinal herbs may be related to inhibition of fatty acid synthase. Life Sc 2004; 74(19): 2389-10. http://dx.doi.org/10.1016/j.lfs.2003.09.064
 Kawata K, Takehira Y, Kobayashi Y, Kitawaga M, Yamada M, Hanajima K,et al., Three cases of liver injury caused by Sennomotokounou, a Chinese dietary supplement for weight loss.Intern Med 2003; 42(12): 1188-4. http://dx.doi.org/10.2169/internalmedicine.42.1188
 Nadir A, Agrawal S, King PD, Marshall JB. Acute Hepatitis associated with the use of a Chinese herbal product, mahuang. Am J Gastroentrol 1996; 91(7): 1436-2.
 Wu AHB editor.Tietz clinical guide to laboratory tests.4th ed.St Louis; W.B. Saunders Co 2006.
 Lee WM. Drug- induced hepatotoxicity. N Engl J Med 2003; 349: 474-11. http://dx.doi.org/10.1056/NEJMra021844
 Chernecky CC, Berger BJ. Laboratory Tests and Diagnostic Procedures. 5th ed. St.Louis: W.B. Saunders; 2008.
 El Agraa SE, Badawi SM, Adam SE. Preliminary observations on experimental Ruta graveolens toxicosis in Nubian goats. Animal Health Prod 2002; 34(4): 271-10. http://dx.doi.org/10.1023/A:1015667616944
Ruqaiya Hasan, Aisha Javaid and Saqiba Fatima, Department of Physiology, University of Karachi, Karachi - 75270, Pakistan, Address corresponding to this author at the Department of Physiology, University of Karachi, Karachi-75270, Pakistan; Tel: 03002521736; E-mail: email@example.com, Received on 29-11-2011, Accepted on 08-12-2011, Published on 24-01-2012, DOI: http://dx.doi.org/10.6000/1927-5129.2012.08.01.010, 2012 Hasan et al.; Licensee Lifescience Global.
This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
|Printer friendly Cite/link Email Feedback|
|Author:||Hasan, Ruqaiya; Javaid, Aisha; Fatima, Saqiba|
|Publication:||Journal of Basic & Applied Sciences|
|Date:||Jun 30, 2012|
|Previous Article:||Anti-hyperlipidemic Activity of Carissa carandas (Auct.) Leaves Extract in Egg Yolk Induced Hyperlipidemic Rats.|
|Next Article:||Clinical Profile of Child and Adolescent (less than 16 years) Psychotic Disorders at a Tertiary Care Centre In India.|