Partially purified non-polar phytocomponents from Aloe barbadensis Mill. gel restores metabolic and reproductive comorbidities in letrozole-induced polycystic ovary syndrome rodent model- an “in-vivo” study

Abstract

Ethnopharmacological relevanceIn India, Kumaryasava, a popular Aloe barbadensis Mill. gel preparation has therapeutic value in treatment of female reproductive disorders like menstrual disturbances and menopausal problems. Despite their widespread use, only a limited number of studies have probed into the scientific evidence for their varied bioactivities. In this regard, studies have demonstrated that Aloe vera gel has the potential to modulate steroidogenic activity in letrozole induced polycystic ovary syndrome (PCOS) rat. However, isolation and identification of the bioactive molecule/s from Aloe vera gel and studying their molecular targets will underpin the treatment regime for PCOS. Material and methodsThe Partially Purified Non-Polar Phytocomponents (PPNPP)- LP1 and LP3 were isolated from the petroleum ether extract of Aloe vera gel by column chromatography. Based upon the GC-MS analysis, LP1 and LP3 comprised of n-Hexadecanoic acid and Campesterol acetate with an abundance of 97.07%, and 96.07% respectively. For evaluation of their bioactivities, eighty 3–4 months female Balb/c mice were classified as 10 groups with 8 animals in each group. Groups were control (C), PCOS (0.5 mg/kg/day Letrozole orally for 21days), PCOS treated orally for 60 days with Aloe vera gel (AVG) (10 mg/kg/day) (PCOS + AVG), PCOS treated orally for 60 days with petroleum ether extract (PE) of Aloe vera gel (25 μg/kg/day) (PCOS + PE), PCOS treated orally for 60 days with LP1 (0.5 μg/kg/day) (PCOS + LP1), PCOS treated orally for 60 days with commercially available pure compound-n-Hexadecanoic acid (HA) (0.5 μg/kg/day) (PCOS + HA), PCOS treated orally for 60 days with LP3 (0.01 μg/kg/day) (PCOS + LP3), PCOS treated orally for 60 days with commercially available pure compound- Campesterol acetate (CA) (0.01 μg/kg/day) (PCOS + CA), PCOS treated orally for 60 days with Metformin (100 mg/kg/day) (PCOS + Metformin) and PCOS treated orally for 60 days with DMSO (Vehicle) (PCOS + DMSO). Body weight, Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, gene expression of gonadotropin receptors (Fshr and Lhr), steroid receptors (Ar, Esr1, Esr2 and Pgr) and steroidogenic markers (Star, Hsd3b1, Cyp19a1 and Amh) were analysed in the ovaries. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Toxicity markers- SGOT, SGPT and creatinine were also measured at the end of the study. ResultsMice treated with letrozole demonstrated significant increase in body weight, glucose intolerance, fasting insulin levels, HOMA-IR, triglycerides levels as well as testosterone levels, and a significant decline in the progesterone levels as compared to the control animals. PCOS animals also exhibited arrested estrus cyclicity, disrupted ovarian histopathology with the presence of multiple peripheral cysts and abnormal gene expression of gonadotropin receptor, steroid receptor and steroid markers. Oral administration of AVG, PE extract of AVG, LP3 and metformin greatly alleviated these complications in PCOS animals. ConclusionThe above findings indicate the effectiveness of LP3, isolated from Aloe vera gel against letrozole induced PCOS in mice and may be used in the treatment of PCOS as an alternative to metformin.