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

Abstract

Kelulut honey (KH) has been proven to have excellent antioxidative and anti-inflammatory properties with unique physicochemical characteristics. Therefore, we investigated the isolated and combined effects of KH, metformin, or clomiphene in alleviating oxidative stress and reproductive and metabolic abnormalities in polycystic ovary syndrome (PCOS). Female Sprague-Dawley (SD) rats were given 1 mg/kg/day of letrozole for 21 days to induce PCOS. PCOS rats were then divided into six treatment groups: untreated, metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were administered orally for 35 days. The physicochemical characteristics of KH were assessed through hydroxymethylfurfural, free acidity, diastase number, moisture content, sugar profile, metals, and mineral compounds. Additionally, we determined the semivolatile organic compounds present in KH through gas chromatography-mass spectrometry (GC/MS) analysis. KH and its combination with metformin or clomiphene were shown to improve the oestrus cycle, hormonal profile, and oxidative stress in PCOS rats. However, KH did not reduce the fasting blood glucose, insulin, and body weight gain in PCOS rats. These findings may provide a basis for future studies to discover the potential use of KH as a complementary treatment for women with PCOS.

Kelulut Honey Improves Folliculogenesis, Steroidogenic, and Aromatase Enzyme Profiles and Ovarian Histomorphology in Letrozole-Induced Polycystic Ovary Syndrome Rats

“…It has been reported that hyperandrogenism is the main factor that contributes to aromatase deficiency in women with PCOS [ 10 ]. Previously, KH was shown to reduce hyperandrogenism in PCOS rats [ 36 ] which might explain its role in restoring the aromatase expression in this study. However, the specific molecular pathway mediated by KH remains to be elucidated.…”

“…These results further validate our preliminary study findings on KH’s beneficial effect on PCOS rats’ ovarian histology [ 39 ]. Previously, KH was reported to improve oxidative stress status and normalise the hormonal and oestrus cycle disturbances in PCOS-induced rats [ 36 ]. These hormonal and oestrus cycle corrections bring back physiological healthy folliculogenesis, which is manifested by improvement in folliculogenesis-related factors and histology findings in this study.…”

“…Furthermore, it has been shown that LH hypersecretion is among the causes of Cyp17a1 overexpression [ 66 ]. Recently, KH has been proven to reduce the elevated LH level in PCOS rats [ 36 ], which might be related to the KH effect on Cyp17a1. Moreover, Tualang honey was reported to regulate the hypothalamic–pituitary–adrenal axis in ovariectomised rats [ 67 ].…”

“…It has been revealed that stingless bee honey, including KH, is predominantly composed of the unusual biologically active disaccharide trehalulose, a highly active antioxidant with a low glycaemic and insulinemic index [ 34 , 35 ]. Besides, a previous study demonstrated that KH contained phytochemical components such as 2,4-Di-tert-butyl phenol and octadecanoic acid, with antioxidant activity that could ameliorate the oxidative stress status of PCOS rats by improving catalase, superoxide dismutase, and glutathione peroxidase levels [ 36 ] In addition, KH is also found to be effective for reproductive health, as KH supplementation has been shown to improve the sperm quality of diabetic rats [ 37 ]. In another study, KH supplementation for pregnant women was reported to be safe and increase the haemoglobin level of pregnant women [ 38 ].…”

“…Previously, we have demonstrated that KH could normalise the disturbances in the hormones, oestrus cycle, and ovarian histomorphology in letrozole-induced PCOS rats [ 36 , 39 ]. With KH’s positive effect on the primary pathogenesis of PCOS, this present study examined the effects of isolated and combined KH, metformin, and clomiphene in improving folliculogenesis, aromatase, and steroidogenic enzyme profiles and ovarian histomorphology in letrozole-induced PCOS rats.…”