Synergistic Action of Virgin Coconut Oil and Clomiphene in Reversing Endocrine Dysregulation in Letrozole-Model of Polycystic Ovarian Syndrome in Rats: Role of Nrf2/HMOX-1 Pathway

다국어 초록 (Multilingual Abstract)

Polycystic ovarian syndrome (PCOS) is an endocrine disorder in women’s reproductive age. Currently, thepathophysiology of PCOS is unclear, and the limited treatment options are unsatisfactory. Virgin coconut oil (VCO) isfunctional food oil associated with pharmacological effects in reproductive disorders. Therefore, we aimed to evaluatewhether VCO could enhance clomiphene (CLO) therapy against PCOS in female rats. Rats were randomly divided: (1)Control, (2) PCOS model, (3) PCOS + CLO, (4) PCOS + VCO, and (5) PCOS + CLO + VCO. The PCOS was induced viadaily letrozole (1 mg/kg, orally) administration for 21 days. After the PCOS induction, CLO, VCO, and CLO + VCO wereadministered from days 22 to 36. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone(FSH), luteinizing hormone (LH), testosterone, estrogen, progesterone, and prolactin were estimated. Polymerase chainreaction gene expression for nuclear factor-erythroid-related factor 2, heme oxygenase-1 (HO-1), catalase (CAT), glutathionereductase (GSR), LH receptor (LHr), androgen receptor (AR), tumor necrosis factor-alpha (TNF-a), interleukin-1b (IL-1b),and caspase-3 were analyzed. The letrozole-induced PCOS caused considerable increases in GnRH, LH, prolactin, estrogen,and testosterone, whereas FSH decreased significantly compared to the control. The gene expression of Nrf2, HO-1, CAT, andGSR were markedly diminished, while IL-1b, TNF-a, caspase-3, AR, and LHr prominently increased compared to control.
Interestingly, the CLO and VCO separately exerted anti-inflammatory and endocrine balance effects. However, VCOenhancedCLO effect in LH, prolactin and testosterone, Nrf2, HO-1, CAT, GSR, and AR. VCO may synergize with CLO todepress hyperandrogenism and oxidative inflammation in PCOS.