{"title":"Meta-analysis and network pharmacology study of Xiaoke Pill in the treatment of type 2 diabetes mellitus","authors":"Xue Zhao, Yi Zhang, Pengling Ge","doi":"10.1016/j.eujim.2025.102502","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Xiaoke Pill is a combination Chinese and Western medicine formula that combines seven Chinese herbal medicines with glibenclamide. Xiaoke Pill is widely used in China for the treatment of type 2 diabetes mellitus (T2DM), however, its overall effectiveness and mechanisms of action are yet to be fully evaluated. We conducted a systematic review to evaluate the clinical effectiveness of Xiaoke Pill compared to Western medicine only and explore its potential mechanisms of action by using network pharmacology.</div></div><div><h3>Methods</h3><div>Randomized controlled trials (RCTs) of Xiaoke Pill in the treatment of T2DM were obtained by searching eight databases: China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database, China Biomedical Medicine Disc (CBM), PubMed, Embase, Cochrane Library and Web of Science. A meta-analysis was performed utilizing RevMan 5.4.1 software. The active ingredients and related targets of Xiaoke Pill were obtained by using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets for T2DM were acquired using the GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape 3.7.2 software. GO enrichment analysis and KEGG pathway analysis were performed using R 3.6.1 software.</div></div><div><h3>Results</h3><div>Twenty-three RCTs with a total of 2946 patients were included. The results of meta-analysis showed that Xiaoke Pill had significant clinical advantages in the treatment of T2DM. Compared with the use of Western medicine only, it shows better efficacy in regulating blood sugar, reducing blood lipids, and improving efficacy. The results of network pharmacology showed that neokadsurac acid A, formononetin, Schottenol were the key ingredients of Xiaoke Pill in the treatment of T2DM. The core targets were EGFR, SRC, STAT3. It mainly included prostate cancer, PI3K-Akt and HIF-1 signaling pathway.</div></div><div><h3>Conclusions</h3><div>Compared with Western medicine only, the clinical advantages of Xiaoke Pill in the treatment of T2DM may stem from the synergistic effect of Chinese and Western medicine components and their multi-component, multi-target and multi-pathway regulatory mechanisms. However, its improvement in blood glucose may not reach the clinically significant level, and its clinical significance still needs to be verified by more related studies.</div></div>","PeriodicalId":11932,"journal":{"name":"European Journal of Integrative Medicine","volume":"77 ","pages":"Article 102502"},"PeriodicalIF":1.7000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Integrative Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S187638202500054X","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Xiaoke Pill is a combination Chinese and Western medicine formula that combines seven Chinese herbal medicines with glibenclamide. Xiaoke Pill is widely used in China for the treatment of type 2 diabetes mellitus (T2DM), however, its overall effectiveness and mechanisms of action are yet to be fully evaluated. We conducted a systematic review to evaluate the clinical effectiveness of Xiaoke Pill compared to Western medicine only and explore its potential mechanisms of action by using network pharmacology.
Methods
Randomized controlled trials (RCTs) of Xiaoke Pill in the treatment of T2DM were obtained by searching eight databases: China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database, China Biomedical Medicine Disc (CBM), PubMed, Embase, Cochrane Library and Web of Science. A meta-analysis was performed utilizing RevMan 5.4.1 software. The active ingredients and related targets of Xiaoke Pill were obtained by using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets for T2DM were acquired using the GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape 3.7.2 software. GO enrichment analysis and KEGG pathway analysis were performed using R 3.6.1 software.
Results
Twenty-three RCTs with a total of 2946 patients were included. The results of meta-analysis showed that Xiaoke Pill had significant clinical advantages in the treatment of T2DM. Compared with the use of Western medicine only, it shows better efficacy in regulating blood sugar, reducing blood lipids, and improving efficacy. The results of network pharmacology showed that neokadsurac acid A, formononetin, Schottenol were the key ingredients of Xiaoke Pill in the treatment of T2DM. The core targets were EGFR, SRC, STAT3. It mainly included prostate cancer, PI3K-Akt and HIF-1 signaling pathway.
Conclusions
Compared with Western medicine only, the clinical advantages of Xiaoke Pill in the treatment of T2DM may stem from the synergistic effect of Chinese and Western medicine components and their multi-component, multi-target and multi-pathway regulatory mechanisms. However, its improvement in blood glucose may not reach the clinically significant level, and its clinical significance still needs to be verified by more related studies.
期刊介绍:
The European Journal of Integrative Medicine (EuJIM) considers manuscripts from a wide range of complementary and integrative health care disciplines, with a particular focus on whole systems approaches, public health, self management and traditional medical systems. The journal strives to connect conventional medicine and evidence based complementary medicine. We encourage submissions reporting research with relevance for integrative clinical practice and interprofessional education.
EuJIM aims to be of interest to both conventional and integrative audiences, including healthcare practitioners, researchers, health care organisations, educationalists, and all those who seek objective and critical information on integrative medicine. To achieve this aim EuJIM provides an innovative international and interdisciplinary platform linking researchers and clinicians.
The journal focuses primarily on original research articles including systematic reviews, randomized controlled trials, other clinical studies, qualitative, observational and epidemiological studies. In addition we welcome short reviews, opinion articles and contributions relating to health services and policy, health economics and psychology.