Arpi Dey is currently a PhD student at the Department of Biochemistry, The Maharaja Sayajirao University of Baroda, India. She has been extensively trained in the domain of reproductive endocrinology. She has contributed greatly to the development of novel herbal therapeutics by exploring the knowledge of Indian heritage of Ayurveda. She has hand-on expertise in animal handling, phytochemistry, molecular biology and cell-culture techniques. She has two citations and seven poster presentations to her credit. Her research will be helpful in identification of a new and naturally derived drug target and add to its overall potential and economic viability at national and international level for a female infertility disorder like PCOS.
Statement of the Problem: Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive disorder which affects 4-12% of women and is a leading cause of female infertility worldwide. PCOS is related to dyslipidemia, hyperandrogenism and hyperinsulinemia. Treatment of these dysfunctions is by administration of steroid analogues and insulin sensitizers. However, the use of these synthetic drugs gives rise to severe side effects. Hence, there is an immediate pre-requisite of an alternative herbal therapy. The purpose of this study is to understand the role of phytosterols isolated from Aloe barbadensis Mill., towards management of PCOS. Methodology & Theoretical Orientation: Aloe vera gel was extracted used petroleum ether and the extract thus obtained was fractionated using silica gel column chromatography. Phytochemical screening, thin layer chromatograph, HPTLC and GC/MS were done to characterize the obtained phytosterols. Letrozole (0.5 mg/kg body weight) induced PCOS mouse model was fed orally with the isolated phytosterol for 60 days. After completion of the treatment, several metabolic as well as reproductive parameters were evaluated. Findings: Detailed phytochemical screening demonstrated the presence of several phytosterols such as beta-sitosterol, stigmasterol and campesterol. Upon treatment with the isolated phytosterols, letrozole induced PCOS mouse model showed an improvement in the glucose sensitivity, restored lipid profile and estrus cyclicity, decreased the serum testosterone levels and increased the serum progesterone and estradiol levels. The animals also exhibited disappearance of the peripheral cysts, which is a hallmark of PCOS. The phytosterols elicit their effectiveness by getting bio-transformed into oxysterols, which can further influence molecular pathways that mainly regulate steroidogenesis and lipid metabolism. Conclusion & Significance: This study is first of its kind which demonstrates the direct effect of phytosterols isolated from Aloe vera gel at molecular level towards management of PCOS, thereby, adding to its overall potential and economic viability at national and international level.
Layanne C C Arauj has her graduation degree in Biomedicine, Masters in Cell and Molecular Biology and she is currently a Doctoral student in Human Physiology at the Biomedical Sciences Institute of the University of São Paulo, working on various subjects like obesity, insulin resistance, hepatic steatosis and intestinal microbiota in the Laboratory of Intracellular Signaling.
We investigated the effect of the herbal extract Uncaria tomentosa (Ut) (50 mg/kg, crude extract, for 5 consecutive days) in two mice models of obesity: high fat diet (DIO) fed mice and the genetic ob/ob mice. Both obese mice exhibited diabetes (151±4 mg*dL-1 vs. 90±2 mg*dL-1 and 205±15 mg/dL vs 163±11 mg/dL, p<0.05, respectively) and insulin resistance (Kitt: 4.0±0.1%*min-1 vs. 0.5±0.3%*min-1, p<0.05, respectively). The Ut treatment induced a 1.8-fold rise in insulin sensitivity in the DIO mice to similar value to that found in the lean group 5.3±0.5% * min-1 and 20% reduction in the fasting glycaemia of both obese mice. The DIO group had 30% and 50% reduction in the protein expression of IR and IRS-1 protein levels respectively, as compared with the SD group (100%) (p<0.05). The stoichiometric rate of IRS-1 phosphorylation in the 307-serine aminoacyl residue was increased in DIO animals as compared to SD group (145±9% vs. 100±10%, respectively, p<0.05). The Ut treatment reduced the serine phosphorylation of IRS-1 by 25% and by 40%, in the liver of DIO and of ob/ob mice respectively. The Ut treatment improved the inflammatory balance in the liver of both obese animals. There were 20% reduction in the pro-inflammatory index (mRNA IL1b/IL10) associated to 12% reduction in the pro-macrophage activation (mRNA F4/80/Arginase1) in the DIO mice, and even more pronounced reduction in the pro-macrophage activation to 40% in the ob/ob. Results herein reported prompted to the conclusion that the improvement in insulin sensitivity induced by the Uncaria tomentosa crude extract is associated with a reduction in inflammatory index in the liver of obese mice.