Zuogui Wan attenuates ovariectomy-induced osteoporosis via the GH/IGF1 axis and related pathways

European Journal of Medicinal Chemistry Reports Pub Date : 2025-04-07 DOI:10.1016/j.ejmcr.2025.100264

Yujie Ma , Pei Li , Changheng Song , Yuhan Wang , Qiqi Yan , Ying Yang , Wenjie Li , Xinyu Wan , Ruyuan Zhu , Jiayi Ma , Yanjing Chen , Haixia Liu , Zhiguo Zhang

{"title":"Zuogui Wan attenuates ovariectomy-induced osteoporosis via the GH/IGF1 axis and related pathways","authors":"Yujie Ma , Pei Li , Changheng Song , Yuhan Wang , Qiqi Yan , Ying Yang , Wenjie Li , Xinyu Wan , Ruyuan Zhu , Jiayi Ma , Yanjing Chen , Haixia Liu , Zhiguo Zhang","doi":"10.1016/j.ejmcr.2025.100264","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Zuogui Wan (ZGW)—one of the classic Chinese formulas—is clinically used to treat osteoporosis (OP). The current investigation aimed to analyze the phytochemical profile of ZGW and to elucidate its mechanisms of action in counteracting OP induced by ovariectomy (OVX) in rats.</div></div><div><h3>Methods</h3><div>The UPLC-MS/MS method was employed to determine the unique qualitative profile of the compounds. OVX rats were subjected to ZGW treatment for 12 weeks. Changes in body weight and bone protective effects were evaluated using various assays, including Vaginal smear assay, HE staining, Micro-CT imaging, and biomechanical testing. The related genes and proteins were validated using RT-qPCR, IHC, and Western blot.</div></div><div><h3>Results</h3><div>The UPLC-MS/MS analysis identified 2091 compounds, and the integral correction diagram showed 23 metabolites. ZGW treatment effectively ameliorated the diminished bone mineral density and compromised bone microstructures observed in OVX rats. Furthermore, ZGW administration to OVX rats increased bone tissue expression levels of RUNX2, BMP2, OSX, OC, and OPG. Moreover, ZGW administration in OVX rats restored the disturbed GH/IGF1 axis. Also, it activated PI3K/AKT signaling pathway and YAP/TAZ signaling pathway.</div></div><div><h3>Conclusion</h3><div>ZGW may exert its anti-OP effects by regulating the GH/IGF1 axis and its related signaling pathways.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"14 ","pages":"Article 100264"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772417425000202","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Zuogui Wan (ZGW)—one of the classic Chinese formulas—is clinically used to treat osteoporosis (OP). The current investigation aimed to analyze the phytochemical profile of ZGW and to elucidate its mechanisms of action in counteracting OP induced by ovariectomy (OVX) in rats.

Methods

The UPLC-MS/MS method was employed to determine the unique qualitative profile of the compounds. OVX rats were subjected to ZGW treatment for 12 weeks. Changes in body weight and bone protective effects were evaluated using various assays, including Vaginal smear assay, HE staining, Micro-CT imaging, and biomechanical testing. The related genes and proteins were validated using RT-qPCR, IHC, and Western blot.

Results

The UPLC-MS/MS analysis identified 2091 compounds, and the integral correction diagram showed 23 metabolites. ZGW treatment effectively ameliorated the diminished bone mineral density and compromised bone microstructures observed in OVX rats. Furthermore, ZGW administration to OVX rats increased bone tissue expression levels of RUNX2, BMP2, OSX, OC, and OPG. Moreover, ZGW administration in OVX rats restored the disturbed GH/IGF1 axis. Also, it activated PI3K/AKT signaling pathway and YAP/TAZ signaling pathway.

Conclusion

ZGW may exert its anti-OP effects by regulating the GH/IGF1 axis and its related signaling pathways.

查看原文本刊更多论文

左归丸通过GH/IGF1轴及其相关通路减轻卵巢切除术所致骨质疏松

中药复方左归丸是治疗骨质疏松症的经典方药之一。本研究旨在分析ZGW的植物化学特征，并阐明其在大鼠卵巢切除（OVX）诱导的OP中的作用机制。方法采用超高效液相色谱-质谱联用技术对化合物进行定性分析。OVX大鼠给予ZGW治疗12周。体重变化和骨骼保护作用通过各种检测方法进行评估，包括阴道涂片检测、HE染色、Micro-CT成像和生物力学测试。采用RT-qPCR、免疫组化和Western blot对相关基因和蛋白进行验证。结果UPLC-MS/MS分析鉴定出2091个化合物，积分校正图显示23个代谢物。ZGW治疗有效改善OVX大鼠骨密度下降和骨微结构受损。此外，给药ZGW增加了OVX大鼠骨组织中RUNX2、BMP2、OSX、OC和OPG的表达水平。此外，在OVX大鼠中给予ZGW可以恢复受干扰的GH/IGF1轴。激活PI3K/AKT信号通路和YAP/TAZ信号通路。结论zgw可能通过调控GH/IGF1轴及其相关信号通路发挥抗op作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Medicinal Chemistry Reports

CiteScore

4.50

自引率

0.00%

发文量