The transcriptomic-based disease network reveals synergistic therapeutic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus.
10.1016/S1875-5364(25)60935-6
- Author:
Qian CHEN
1
;
Shuying ZHANG
2
;
Xuanxi JIANG
3
;
Jie LIAO
1
;
Xin SHAO
1
;
Xin PENG
4
;
Zheng WANG
1
;
Xiaoyan LU
5
;
Xiaohui FAN
6
Author Information
1. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314100, China.
2. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.
3. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
4. Ningbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo 315100, China.
5. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: Luxy@zju.edu.cn.
6. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; National Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314100, China. Electronic address: fanxh@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
Alkaloids;
Component compatibility;
Network pharmacology;
Total alkaloids from Coptis chinensis;
Total ginsenosides from Panax ginseng;
Type 2 diabetes mellitus
- MeSH:
Animals;
Panax/chemistry*;
Ginsenosides/administration & dosage*;
Diabetes Mellitus, Type 2/metabolism*;
Mice;
Male;
Alkaloids/pharmacology*;
Coptis/chemistry*;
Drug Synergism;
Insulin Resistance;
Mice, Inbred C57BL;
Humans;
Transcriptome/drug effects*;
Blood Glucose/metabolism*;
Hypoglycemic Agents/administration & dosage*;
Drugs, Chinese Herbal/administration & dosage*;
Hepatocytes/metabolism*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(8):997-1008
- CountryChina
- Language:English
-
Abstract:
Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
