title: Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells.
abstract: Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhi-Shen
authors.initials: ZS
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Feng-Guo
authors.initials: FG
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China. Electronic address: spma2009hz@yahoo.cn.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Nanjing 210009, China. Electronic address: xiaojunxu2000@163.com.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
mesh_terms: D000818:Animals; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D008593:Menopause / Q000187:drug effects* / Q000378:metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D007328:Insulin; D005947:Glucose
keywords: Estrogen receptor; Glucose tolerance; Islet β cell; Jiawei Erzhiwan; Menopausal metabolic syndrome