Effects of Kelulut Honey on Oestrus Cycle Regulation and Histomorphological Changes in Letrozole-Induced Polycystic Ovary Syndrome Rats: A Preliminary Study

Abstract

Polycystic ovary syndrome (PCOS) is a complex reproductive, metabolic, and endocrine disorder that affects women of reproductive age. Kelulut honey is stingless bee honey that possesses anti-inflammatory, anti-cancer, anti-diabetic, and potent antioxidative activities in most conditions. However, its value in improving PCOS remains to be elucidated. Thus, this preliminary study aimed to determine the effective dose of Kelulut honey in oestrus cycle regulation and ovarian histomorphological changes in letrozole-induced PCOS rats. PCOS was induced in all-female Sprague Dawley (SD) rats with 1 mg/kg/day of letrozole except for the control group for 21 days. Kelulut honey was then orally administered to the PCOS rats at the dose of 0.5, 1, or 2 g/kg/day, respectively, for 35 days. The oestrous cycle was determined through vaginal smears, while ovarian histomorphological changes were observed by haematoxylin and eosin (H&E) staining. The untreated PCOS rats were characterised by irregular oestrous cyclicity, hyperglycaemia, and aberrant ovarian histology. In this study, Kelulut honey (1 g/kg/day) increased the number of corpus luteum and antral follicles (p < 0.05), improved the cystic follicle, and normalised the oestrus cycle (p < 0.05). This preliminary study demonstrated that Kelulut honey, particularly at a dose of 1 g/kg/day, has the potential to alleviate oestrus cycle dysregulation and ovarian histomorphological changes occurring in PCOS.

Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats

“…Furthermore, the combination of KH with metformin and clomiphene showed significant normalisation of the oestrus cycle. These results strengthen our previous finding which revealed oestrus cycle improvement in PCOS-induced rats treated with KH [ 28 ]. Previously, Tualang honey has been demonstrated to improve the bisphenol A-induced disruption of the oestrus cycle [ 64 ].…”

“…As demonstrated in our previous study [ 28 ], KH did not affect the blood glucose levels in PCOS rats. This agrees with previous observations which found that daily intake of KH for 30 days caused no changes in fasting blood glucose in patients who have impaired fasting blood glucose [ 60 ].…”

“…The second group ( n = 36) was administered with 1 mg/kg/day of letrozole orally, once daily for 21 days, to induce PCOS as reported in a previous study [ 33 ]. As validated in our previous study, PCOS was induced in all rats administered with 1 mg/kg/day of letrozole for 21 days, determined by examining the dioestrous days, blood glucose levels, and ovarian histology [ 28 ].…”

“…The doses of metformin (500 mg/kg/day) and clomiphene (2 mg/kg/day) were based on the study by Ndeingang et al [ 34 ]. KH dose (1 g/kg/day) and treatment duration were determined from our pilot study [ 28 ]. Metformin is used for insulin resistance in women with PCOS, whereas clomiphene is used to induce ovulation [ 24 ].…”

“…This finding strengthens the potential use of nutraceuticals in treating typical symptoms of PCOS and the need for more research to be conducted in this field. Recently, we found that KH could improve the regulation of the oestrus cycle and ovarian histomorphological alterations in rats with letrozole-induced PCOS [ 28 ]. In view of these promising effects, the current study aimed to focus on the antioxidative effect of KH on letrozole-induced PCOS rats.…”