ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2025
Mechanisms of Dangguiliuhuang Tang in Streptozotocin-Induced Type 2 Diabetes Mellitus Mice Based on Network Pharmacology, Gut Microbiota, and Experimental Validation.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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