文献类型：期刊文献

英文题名：Gengnianshou formula inhibits estrogen deficiency induced obesity via an HSPA5-associated phosphatidylcholine (PC) regulatory pathway: Ethnopharmacological relevance and mechanistic insights from network pharmacology and multi-omics

作者：Zhang, Wei[1,2];Zhang, Wen-tao[1];Fan, Jia-xing[3];Wang, Ya-yun[4];Kang, Meng-jiao[5];Li, Xiang[6];Wang, Shan[7,8];Zhao, Lin-hua[1,9]

第一作者：张维;Zhang, Wei;张伟

通信作者：Zhao, LH[1];Wang, S[2]

机构：[1]China Acad Chinese Med Sci, Guanganmen Hosp, Inst Metab Dis, Beijing, Peoples R China;[2]Gansu Univ Chinese Med, Sch Basic Med, Lanzhou, Gansu, Peoples R China;[3]Jinzhou Med Univ, Sch & Hosp Stomatol, Jinzhou, Liaoning, Peoples R China;[4]Changchun Univ Chinese Med, Northeast Asia Res Inst Tradit Chinese Med, Minist Educ, Changchun, Jilin, Peoples R China;[5]Zhejiang Chinese Med Univ, Sch Clin Med 1, Hangzhou, Zhejiang, Peoples R China;[6]Peking Univ, Sch Basic Med Sci, Dept Human Anat Histol & Embryol, Hlth Sci Ctr, Beijing, Peoples R China;[7]China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China;[8]China Japan Friendship Hosp, Natl Ctr Integrat Med, Beijing, Peoples R China;[9]Changchun Univ Chinese Med, Affiliated Hosp, Dept Endocrinol, Changchun, Jilin, Peoples R China

第一机构：China Acad Chinese Med Sci, Guanganmen Hosp, Inst Metab Dis, Beijing, Peoples R China

通信机构：[1]corresponding author), China Acad Chinese Med Sci, Guanganmen Hosp, Inst Metab Dis, Beijing, Peoples R China;[2]corresponding author), China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China.

年份：2026

卷号：369

外文期刊名：JOURNAL OF ETHNOPHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-105040689555);WOS:【SCI-EXPANDED(收录号:WOS:001791156600001)】；

基金：This study was supported by Scientific and Technological Innovation project of China Academy of Chinese Medical Sciences (CI2021B008, China) , Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-D-202001) , Dose-Effect Study of Prescriptions of China Association of Chinese Medicine (No: 202428-003, China) .

语种：英文

外文关键词：Gengnianshou formula; Perimenopausal obesity; Network pharmacology; Multi-omics; Phosphatidylcholine; Estrogen deficiency

摘要：Ethnopharmacological relevance: Gengnianshou Formula (GNS), a traditional Chinese medicine formula composed of 9 herbs, has long been used for regulating menopausal syndromes based on the TCM theory. However, its mechanistic basis for ameliorating perimenopausal obesity (a common estrogen deficiency-induced metabolic disorder) remains unelucidated. Aim of the study: This study aimed to investigate the anti-obesity effects of GNS under estrogen-deficient conditions and to explore the potential involvement of HSPA5 and phosphatidylcholine (PC) metabolism using network pharmacology and multi-omics approaches. Materials and methods: An ovariectomized (OVX) rat model was established using female Sprague-Dawley rats, which were randomly assigned to six groups (n = 6 per group) to evaluate the therapeutic effects of GNS. Network pharmacology analysis was conducted to identify potential targets. Transcriptomics and lipidomics analyses were integrated to explore molecular alterations. In vitro experiments using human adipose-derived stem cells (hADSCs) under estrogen-deprived conditions were performed to functionally validate the role of HSPA5 through siRNA-mediated knockdown, followed by Oil Red O staining and gene expression analysis. Results: The OVX model successfully induced obesity, as evidenced by significant increases in body weight, visceral and subcutaneous white adipose tissue (vWAT/sWAT) volume, and adipocyte hypertrophy. GNS dose-dependently attenuated OVX-induced obesity phenotypes and partially improved lipid metabolic disorders, including reduced serum TC levels and adipose lipid accumulation. Network pharmacology identified HSPA5 as a potential key target. Multi-omics analysis revealed significant alterations in lipid metabolism, particularly in PC-related species, which were associated with HSPA5 expression changes. Functional experiments demonstrated that silencing HSPA5 attenuated lipid accumulation and downregulated adipogenic markers, including PPAR gamma and C/EBP alpha, under estrogen-deficient conditions. Conclusion: These findings support a functional role of HSPA5 in regulating adipogenesis, while alterations in PC metabolism may represent associated downstream metabolic changes. GNS ameliorates estrogen deficiency-induced obesity, potentially involving HSPA5 and PC metabolism. This study provides integrative evidence supporting HSPA5 as a functional regulator in this context, while highlighting a possible link to PC metabolic remodeling.