Investigating the Systems-Level Effect of Pueraria lobata for Menopause-Related Metabolic Diseases Using an Ovariectomized Rat Model and Network Pharmacological Analysis.

Ji Hong Oh,Ji Yun Baek,Do Hwi Park,Hye Lim Lee,Jeong-Eun Yoo,Seon-Eun Baek,Chang-Eop Kim,Tuy An Trinh,Ki Sung Kang,Won-Yung Lee

doi:10.3390/biom9110747

Abstract

This study was conducted to evaluate the biological activities of Pueraria lobata (PL) on menopause-related metabolic diseases and to explore the underlying mechanism of PL by network pharmacological analyses. We used ovariectomized (OVX) rats as a postmenopausal model and administered PL at different doses (50, 100, and 200 mg/kg). In OVX rats, decreased uterine weights and PPAR-γ (peroxisome proliferator-activated receptor-gamma) mRNA expression in the thigh muscle were significantly recovered after PL administration. PL also significantly alleviated OVX-induced increases in total cholesterol, triglyceride, alanine aminotransferase (ALT/GPT), and aspartate aminotransferase (AST/GOT) levels. To identify the systems-level mechanism of PL, we performed network pharmacological analyses by predicting the targets of the potential bioactive compounds and their associated pathways. We identified 61 targets from four potential active compounds of PL: formononetin, beta-sitosterol, 3’-methoxydaidzein, and daidzein-4,7-diglucoside. Pathway enrichment analysis revealed that among female sex hormone-related pathways, the estrogen signaling pathways, progesterone-mediated oocyte maturation, oxytocin signaling pathways, and prolactin signaling pathways were associated with multiple targets of PL. In conclusion, we found that PL improved various indicators associated with lipid metabolism in the postmenopausal animal model, and we also identified that its therapeutic effects are exerted via multiple female sex hormone-related pathways.

Highlights

Menopause is a period when women’s ovarian function gradually declines and female hormones fluctuate and decrease, resulting in irregular menstruation and menopause-related symptoms
To explore the underlying mechanism of Pueraria lobata (PL), we investigated target genes and pathways of PL related to menopause-related metabolic diseases by applying network pharmacology analysis (Figure 1)
It was observed that the PL treatment dose-dependently improved uterine weight in the OVX rats (p = 0.008, 0.0009, and 0.0009 per dose, respectively), which is consistent with red clover (RC)

Summary

Introduction

Menopause is a period when women’s ovarian function gradually declines and female hormones fluctuate and decrease, resulting in irregular menstruation and menopause-related symptoms. Lack of estrogen induces imbalance of energy homeostasis, by assisting energy intake and lipogenesis, depressing energy expenditure, and aggravating insulin secretion and sensitivity [1]. These metabolic changes in menopause mediate the development of chronic diseases such as cardiovascular diseases (CVD), obesity, hyperlipidemia, and fatty liver [2]. While HRT is effective in alleviating most postmenopausal symptoms [7], many women refuse HRT concerning the latent adverse effects and prefer the use of nonhormonal therapies to relieve symptoms after menopause [7,8]. Herb-based therapies were found to be associated with more reductions in the symptoms in menopausal women than in the placebo group in meta-analysis [11]. In a randomized controlled trial, whole soy had a beneficial effect on cardiovascular biomarkers in equol-producing postmenopausal women when compared with the placebo group [12]

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