已发表论文

基于网络药理学、肠道菌群及实验验证的当归六黄汤对链脲佐菌素诱导的 2 型糖尿病小鼠的作用机制

 

Authors Meng X, Bu Z, Li X, Ren J, Dai Y, Zhang S

Received 21 March 2025

Accepted for publication 20 September 2025

Published 22 October 2025 Volume 2025:18 Pages 3907—3930

DOI https://doi.org/10.2147/DMSO.S525913

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Rebecca Baqiyyah Conway

Xianglong Meng,1– 4,* Zhulin Bu,1– 4,* Xiaofen Li,1– 4 Jing Ren,1– 4 Yuting Dai,1– 4 Shuosheng Zhang1– 4 

1College of Chinese Materia Medica and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of China; 2Key Laboratory of Traditional Chinese Medicine Processing in Shanxi Province, Jinzhong, Shanxi, People’s Republic of China; 3Traditional Chinese Medicine Processing Techniques Heritage Base, Jinzhong, Shanxi, People’s Republic of China; 4Research Laboratory of Traditional Chinese Medicine Processing, Inheritance and Innovation, Jinzhong, Shanxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xianglong Meng, Email sszywzh@126.com

Background: Dangguiliuhuang Tang (DGLHT), a classic traditional Chinese medicine formula, has long been used to treat type 2 diabetes mellitus (T2DM). Nevertheless, its therapeutic efficacy, pharmacological foundation, and underlying mechanisms warrant further scientific exploration.
Methods: Ultra-high-performance liquid chromatography coupled with Thermo Vanquish UHPLC-Thermo Q Exactive HFX (UHPLC-QE-MS) was utilized to identify the chemical components of DGLHT. A potential therapeutic network for DGLHT in treating T2DM was constructed using network pharmacology. Untargeted metabolomics techniques were applied to reveal the differential effects of DGLHT on T2DM, and 16S rDNA amplification sequencing technology was used to investigate the differential metabolic regulation of gut microbiota in T2DM mice treated with DGLHT. Molecular biomedical experimental methods were combined to validate and analyze expression levels of the relevant proteins in the liver. A correlation analysis between the active ingredients of DGLHT and the differential gut microbiota was established.
Results: DGLHT improved glycemia, glucose tolerance, and liver injury in T2DM mice. A total of 38 major components were identified. Core targets included mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), non-receptor tyrosine kinase (TNK), C-X-C motif chemokine ligand 8 (CXCL8), and serine/threonine kinase 1 (AKT1). DGLHT significantly altered the serum metabolic profile and gut microbiota composition in T2DM mice. These alterations affected inflammation-related Toll-like receptor signaling pathways, phosphorylation-associated ErbB signaling pathways, and functional substance metabolism related to bile secretion, cholesterol metabolism, biosynthesis of unsaturated fatty acids, protein digestion and absorption, cysteine and methionine metabolism, carbohydrate metabolism, intestinal membrane transport, and amino acid metabolism. DGLHT modulated protein expression in several key signaling pathways, including the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) pathway, phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT)/glucose transporter type 4 (GLUT4) pathway, AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferators-activated receptor γ coactivator 1 alpha (PGC-1α) pathway, and heme oxygenase 1 (HO-1)/superoxide dismutase (SOD2)/catalase (CAT) pathway. The Candida genus and gamma-linolenic acid exhibited the strongest correlation.
Conclusion: DGLHT alleviates T2DM insulin resistance via multi-pathway regulation of inflammation, energy metabolism, and oxidative stress, mediated through metabolic and gut microbiota modulation.

Keywords: DGLHT, metabolism, mechanism, multi-omics