The Molecular Mechanism Underlying the Therapeutic Effect of Dihydromyricetin on Type 2 Diabetes Mellitus Based on Network Pharmacology, Molecular Docking, and Transcriptomics

Xinnian Wen; Chenghao Lv; Runze Zhou; Yixue Wang; Xixin Zhou; Si Qin

doi:10.3390/foods13020344

Foods (Jan 2024)

The Molecular Mechanism Underlying the Therapeutic Effect of Dihydromyricetin on Type 2 Diabetes Mellitus Based on Network Pharmacology, Molecular Docking, and Transcriptomics

Xinnian Wen,
Chenghao Lv,
Runze Zhou,
Yixue Wang,
Xixin Zhou,
Si Qin

Affiliations

Xinnian Wen: Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
Chenghao Lv: College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
Runze Zhou: Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
Yixue Wang: Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
Xixin Zhou: College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
Si Qin: Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China

DOI: https://doi.org/10.3390/foods13020344
Journal volume & issue: Vol. 13, no. 2
p. 344

Abstract

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Type 2 diabetes mellitus (T2DM) is a chronic and complex disease, and traditional drugs have many side effects. The active compound dihydromyricetin (DHM), derived from natural plants, has been shown in our previous study to possess the potential for reducing blood glucose levels; however, its precise molecular mechanism remains unclear. In the present study, network pharmacology and transcriptomics were performed to screen the molecular targets and signaling pathways of DHM disturbed associated with T2DM, and the results were partially verified by molecular docking, RT-PCR, and Western blotting at in vivo levels. Firstly, the effect of DHM on blood glucose, lipid profile, and liver oxidative stress in db/db mice was explored and the results showed that DHM could reduce blood glucose and improve oxidative stress in the liver. Secondly, GO analysis based on network pharmacology and transcriptomics results showed that DHM mainly played a significant role in anti-inflammatory, antioxidant, and fatty acid metabolism in biological processes, on lipoprotein and respiratory chain on cell components, and on redox-related enzyme activity, iron ion binding, and glutathione transferase on molecular functional processes. KEGG system analysis results showed that the PI3K-Akt signaling pathway, IL17 signaling pathway, HIF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway were typical signaling pathways disturbed by DHM in T2DM. Thirdly, molecular docking results showed that VEGFA, SRC, HIF1A, ESR1, KDR, MMP9, PPARG, and MAPK14 are key target genes, five genes of which were verified by RT-PCR in a dose-dependent manner. Finally, Western blotting results revealed that DHM effectively upregulated the expression of AKT protein and downregulated the expression of MEK protein in the liver of db/db mice. Therefore, our study found that DHM played a therapeutic effect partially by activation of the PI3K/AKT/MAPK signaling pathway. This study establishes the foundation for DHM as a novel therapeutic agent for T2DM. Additionally, it presents a fresh approach to utilizing natural plant extracts for chemoprevention and treatment of T2DM.

Published in Foods

ISSN: 2304-8158 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Chemical technology
Website: http://www.mdpi.com/journal/foods

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