Research J. Pharm. and Tech. 16(1): January 2023 385 ISSN 0974-3618 (Print) www.rjptonline.org 0974-360X (Online) RESEARCH ARTICLE Evaluation of Gymnema sylvestre R. Br. against Letrozole Induced Polycystic Ovarian Syndrome in rats Sudhakar Pachiappan 1 , Kothai Ramalingam 1 *, Arul Balasubramanian 2 1 Department of Pharmacology, Vinayaka Mission’s College of Pharmacy, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem - 8, Tamil Nadu, India. 2 Department of Pharmacy Practice, Vinayaka Mission’s College of Pharmacy, Vinayaka Mission’s Research Foundation (Deemed to be University), Salem - 8, Tamil Nadu, India. *Corresponding Author E-mail: kothaiarul@yahoo.co.in ABSTRACT: Objectives: To evaluate the therapeutic potential of Gymnema sylvestre (GS) leaf ethanolic extract against letrozole induced polycystic ovarian syndrome (PCOS) in rats. Methods: Thirty female virgin rats (180 - 250g) with regular estrus cycles were used and divided into five groups of six animals each. Group-I serves as normal control receives 1ml of 0.5% carboxyl methyl cellulose orally; group-II to V were treated with letrozole (1mg/kg/b.w. p.o.) for 21 days to induce PCOS. Induction of PCOS was confirmed by measuring menstrual irregularity. After induction of PCOS, group-II serves as PCOS control, group-III receives metformin (20 mg/kg/b.w. p.o.) as standard, and group- IV to V treated with G. sylvestre ethanolic extract 200mg/kg/b.w. and 400mg/kg/b.w. p.o. respectively for 28 days. After completion of the treatment schedule oral glucose tolerance test was carried out, followed by serum lipid profile (LDL, VLDL, HDL, and TG), and hormonal analysis was carried out. Then the animals have sacrificed and the ovaries were then processed for histological examination. Results: The results of this study exhibited irregularity in the estrus cycle, a significant increase in serum blood glucose, and an altered serum lipid profile in PCOS control. In addition, the PCOS control rats showed a significant increase in serum luteinizing hormone, testosterone, and a decrease in estrogen, follicle-stimulating hormone, and progesterone. These changes were significantly reversed by G. sylvestre in a dose dependent manner. Histopathology of the ovary also showed an almost normal ovary in the treatment groups. Conclusion: In conclusion, the treatment of ethanolic leaf extract of Gymnema sylvestre reduces insulin resistance by improving glucose utilization, regularize menstrual irregularity and promote ovulation by correcting the hormonal irregularities and improve the development of follicles in PCOS condition. KEYWORDS: Gymnema sylvestre, Letrozole, Metformin, Polycystic ovarian syndrome. INTRODUCTION: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinal disorders in women, among that 4- 12% of women affecting at the reproductive age 1,2 . It is characterized by numerous cysts on the ovaries associated with hyperandrogenism, chronic anovulation, insulin insensitivity, and other metabolic abnormalities 3 . Hyperandrogenism and insulin resistance are the major pathological contributors to PCOS. Received on 28.06.2021 Modified on 08.11.2021 Accepted on 14.02.2022 © RJPT All right reserved Research J. Pharm. and Tech 2023; 16(1):385-390. DOI: 10.52711/0974-360X.2023.00066 Insulin resistance not only contributes to the metabolic feature of PCOS but also a contributor of reproductive features through increased production of androgen in theca cells and increasing free androgen by inhibiting the hepatic synthesis of sex hormone-binding globulin (SHBG) in the liver 4 . Metformin is one of the commonly prescribing insulin- sensitizing agents for PCOS women 5 . Apart from the hypoglycaemic effect, it also regularizes the menstrual irregularity, induces ovulation, and reduces the excessive androgen level. Metformin therapy has fewer side effects like hot flushes, bloating, mood swings, joint pain, and arthritis 6 . Due to these limitations, PCOS women are intense to use the alternate medication in association with traditional knowledge to improve the PCOS condition 7 .