EFFECTS OF UNANI ANXIOLYTICS (SOMINA) ON GENERAL REPRODUCTIVE PERFORMANCE AND TERATOLOGY IN RATS
Objective: Somina (herbal medicine) is used in Pakistan as Unani anxiolytics. It is composed of five medicinal plants. The current work was designed to evaluate the general reproductive and teratogenic effects of somina in two consecutive generations of rats according to the OECD guideline.
Methods: Fertility study (a two-phase study) was done in Sprague-Dawley rats. 1st part: three groupsâ€™ female rats (10 rats each group) received different doses orally. First group: The control group (saline), a single oral human dose of somina (2nd group: 285 mg/kg/day) and the high dose of somina (3rd group: 1g/kg/day) during the whole period of gestation till the delivery of pups named as F1 Breed. For the second part of study ten females were selected from each F1 breed (control, somina 285 mg/kg/d, somina 1g/kg/day) and administered the same treatment from day first of mating than the entire period of gestation until F1 breed delivered pups (F2 breed). For F1 and F2 breed the fertility index and litter size were determined. Some of the female rats (F1 and F2) were anesthetized and autopsied. The blood sample was subjected to biochemical analysis and serum liver function test: bilirubin, gamma-glutamyl transferase (Î³GT), alanine aminotransferase (ALT: SGPT), aspartate aminotransferase (AST: SGOT) and alkaline phosphatase (ALP) were measured spectrophotometrically. The uterine growth index, fertility index, and litter size were also measured to evaluate the teratogenic effects of somina treated rats.
Results: The data showed that any significant different (P>0.05) was not found during the maternal examination (uterine growth index, fertility index) and reproductive parameters (litter size, the quantity of fetus, aborted or absorbed fetus) in somina treated rats as compare to control rats (P>0.05). Control and treated Pups did not show any significant (P>0.05) malformation and any congenital defects. Non-significant (P>0.05) changes were observed in liver function test. It was found normal in all groups. Macroscopic autopsy examination also did not reveal any significant (P>0.05) pathological findings in the liver, kidneys, and uterus.
Conclusion: The oral administration of somina during the gestational period of pregnant female rats was not teratogenic/fetotoxic. Any adverse or deleterious effects were not observed at the dose of 285 mg/kg (human dose) or 1g/kg (3times greater than the human dose) during pregnancy, and it is safe in rats.
2. Azmat A, Ahmed M, Zafar N, Ahmad SI. Neuropharmacological profile of Somina (Herbal Drug) in mice and rats. Pakistan J Pharmacol 2008;25:53-8.
3. Azmat A, Ahmed M, Haider S, Haleem DJ, Zafar N, Ahmad SI. Enhanced memory processes under the influence of herbal drug Somina and its effect on brain serotonin. Afr J Pharm Pharmacol 2012;6:2458-63.
4. Jyoti A, Anand K, Sunanda P. Synergistic action of phytochemicals augments their antioxidative efficacy: an in vitro comparative study. Asian J Pharm Clin Res 2013;6 Suppl 4:121-6.
5. Deshpande P, Mohan V, Pore M, Gumaste S, Thakurdesa P. Prenatal developmental toxicity evaluation of Furostanol Saponin Glycoside based standardised fenugreek seed extract during organogenesis period of pregnancy in rats. Int J Pharm Pharm Sci 2016;8:124-9.
6. Agarwal S, Jain A, Jain A, Mourya M, Vandana KC, Jackson P, et al. N-AsthealÂ®, A herbal formula for the treatment of mild asthma: an open, single-centric, noncomparative pilot study for 3 W. Asian J Pharm Clin Res 2014:7:1-6.
7. Walker R. Criteria for risk assessment of botanical food supplements. Toxicol Lett 2004;149:187-95.
8. Palmer ME, Haller C, McKinney PE, Klein-Schwartz W, Tschirgi A, Smolinske SC, et al. Adverse events associated with dietary supplements: an observational study. Lancet 2003;361:101-6.
9. Pittler M, Ernst E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther 2003;18:451-71.
10. Garba SH, Jacks TW, Onyeyili PA, Nggada HA. Embryofetal effects of the methanolic root extract of Cissampelos Mucronata A. rich in rats. J Anamtomy 2014;3:286-93.
11. Turolla MSR, Nascimento ES. InformaÃ§Ãµes toxicolÃ³gicas de alguns fitoterÃ¡pi cosutiliza dos no Brasil. Rev Bras CiÃªn Farm 2006;42:289-306.
12. Ahmed M. Acute toxicity (Lethal Dose 50 Calculation) of herbal drug Somina in rats and mice. Pharmacol Pharm 2015;6:185-9.
13. FDA. Toxicological Principles for the Safety of Food Ingredient â€˜Redbookâ€™. US Food and Drug Administration Centre for Food Safety and Applied Nutrition, Washington DC; 2000.
14. Pfannkuch F, Edwards JA, Wolz E, Marsden E. EGCG (Ro 26-7624/000)--two generation oral (dietary admixture) reproduction toxicity study in the rat. Roche Vitamins Ltd; 2002a.
15. Isbrucker RA, Edwards JA, Wolz E, Davidovich A, Bausch J. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. Food Chem Toxicol 2006;44:651â€“61.
16. Ahmed M, Azmat A. Two-generation reproductive toxicity study of Barrisal (Herbal Drug) on the sprague dawley rats. Annu Rev Res Biol 2014;4:3197-202.
17. Ratnasooriya WD, Dharmasiri MG. Effects of Terminalia catalpa seeds on sexual behaviour and fertility of male rats. Asian J Androl 2000;2:213-9.
18. Kurtz SM. Toxicological studies on Gemfibrozil. Proc Roy Soc Med 1976;69 Suppl 2:15-23.
19. Pawson P. Sedatives. In: Small animal clinical pharmacology (2nd edn). Maddison J, Page S, Church D. eds. Saunders (Elsevier), UK; 2008. p. 113â€“25.
20. Zhang ZJ. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci 2004;75:1659â€“99.
21. Ashamu EA, Salawu EO, Oyewo OO, Alhassan AW, Alamu OA, Adegoke AA. Efficacy of vitamin C and ethanolic extract of Sesamum indicum in promoting fertility in male Wistar rats. J Hum Reprod Sci 2010;3:11â€“4.
22. Mahabadi JA, Bafrani HH, Nikzad H, Taberian A, Salehi M. Effect of diet contains sesame seed on adult wistar rat testis. Int J Morphol 2013;31:197-202.
23. Hari JR, Lakshmi. Therapeutic applications of almonds (Prunus amygdalus L): a review. J Clin Diagnostic Res 2012;6:130-5.
24. Bardhan J, Riar SS, Sawhney RC, Kain AK, Thomas P. Iiavazhagan G. Neem oil: a fertility controlling agent in Rhesus monkey. Indian J Physiol Pharmacol 1991;35:278-80.
25. Sadler TW. Susceptible periods during embryogenesis of the heart and endocrine glands. Environ Health Perspect 2000;108 Suppl 3:555-61.
26. Sirato-Yasumoto N, Katsuta M, Okuyama Y. Effect of sesame seed rich in sesamin and sesamolin on fatty acid oxidation in rat liver. J Agric Food Chem 2001;49:2647.
27. Soni M, Mohanthy PK, Jaliwala YA. The hepatoprotective activity of the fruits of Prunus. Int J Pharm Biosci 2011;2:439-52.
28. Funde SK, Jaju JB, Dharmadhikari SC, Pawar GR. Effect of Lagenaria siceraria fruit extract (Bottle gourd) on hepatotoxicity induced by antitubercular drugs in albino rats. Int J Basic Clin Pharmacol 2013;2:728-34.
29. Hefnawy TM, Ramadan MF. Protective effects of Lactuca sativa ethanolic extract on carbon tetrachloride-induced oxidative damage in rats. Asian Pac J Trop Dis 2013;3:277â€“85.