In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications
Open accessAbstract
ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR), extracted from the traditional medicinal plant Coptis chinensis Franch., has been widely used for the treatment of type 2 diabetes mellitus (T2DM) and its complications. AIM OF THE STUDY: To determine the potential pharmacological mechanisms underlying BBR therapeutic effect on T2DM and its complications by in silico network pharmacology and experimental in vivo validation. MATERIALS AND METHODS: A predictive network depicting the relationship between BBR and T2DM was designed based on information collected from several databases, namely STITCH, CHEMBL, PharmMapper, TTD, Drugbank, and PharmGKB. Identified overlapping targets related to both BBR and T2DM were crossed with information on biological processes (BPs) and molecular/signaling pathways using the DAVID platform and Cytoscape software. Three candidate targets identified with the BBR-T2DM network (RXRA, KCNQ1 and NR3C1) were evaluated in the C57BL/6J mouse model of T2DM. The mice were treated with BBR or metformin for 10 weeks. Weight, fasting blood glucose (FBG), oral glucose tolerance, and expression levels of the three targets were evaluated. RESULTS: A total of 31 targets of BBR that were also related to T2DM were identified, of which 14 had already been reported in previous studies. Furthermore, these 31 overlapping targets were enriched in 21 related BPs and 18 pathways involved in T2DM treatment. The identified BP-target-pathway network revealed the underlying mechanisms of BBR antidiabetic activity were mediated by core targets such as RXRA, KCNQ1, and NR3C1. In vivo experiments further confirmed that treatment with BBR significantly reduced weight and FBG and alleviated insulin resistance in T2DM mice. Moreover, BBR treatment promoted RXRA expression, whereas it reduced KCNQ1 and NR3C1 expression in the liver. CONCLUSION: Using network pharmacology and a T2DM mouse model, this study revealed that BBR can effectively prevent T2DM symptoms through vital targets and multiple signaling pathways. Network pharmacology provides an efficient, time-saving approach for therapeutic research and the development of new drugs.
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Berberine regulates the gut microbiota, which is closely associated with systematic inflammation that adds to the progression of T2DM.
“Additionally, evidence has shown that berberine regulates the gut microbiota as well [14, 15], which is closely associated with systematic inflammation that adds to the progression of T2DM.”
From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [14]
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References 80 · Cited by 57
Research works printed but not linked: 3
- Cao, W.L., Hu, L., Chen, H., Gao, Y.Q., Liang, Y., Wu, Y., Yang, Q.L., Tang, N., Cao, J.S., Xiao, J.H., 2017. Berberine alleviates chronic inflammation of mouse model of type 2 diabetes by adjusting intestinal microbes and inhibiting TLR4 signaling pathway. Int. J. Clin. Exp. Med. 10 (7), 10267-10276.
- Zhou, J., Zhou, S., 2010b. Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes. Eur. J. Pharmacol. 649 (1), 390-397.
- Zhou, J.Y., Zhou, S.W., 2008. Effect of berberine on PPARα/δ/γ expression in type 2 diabetic rat kidney. Prog. Mod. Biomed. 42 (12), 1243-1249.
- Authors
- Di, S., Han, L., An, X., Kong, R., Gao, Z., Yang, Y., Wang, X., Zhang, P., Ding, Q., Wu, H., Wang, H., Zhao, L., & Tong, X.
- Affiliations
- China Academy of Chinese Medical Sciences (CN)
- Beijing Proteome Research Center (CN)
- Changchun University of Chinese Medicine (CN)
- Corresponding author
- Zhao, Linhua
- Tong, Xiaolin
- ORCID
- Venue
- Journal of Ethnopharmacology
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 276
- Pages
- 114180
- ISSN
- 0378-8741 (ISSN-L)
- OpenAlex
- W3158345140
- Cited by
- 57
- References
- 80
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 3
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Ethnopharmacology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- China Academy of Chinese Medical Sciences (ZZ0808004)
- National Natural Science Foundation of China (81973837)
- State Administration of Traditional Chinese Medicine of the People's Republic of China (GZYYGJ2018031, 81774296)
- National Key Research and Development Program of China (2019YFC1709904)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- berberine, type 2 diabetes, Coptis chinensis, diabetes complications, retinoid X receptor alpha, KCNQ1, NR3C1, insulin resistance, fasting blood glucose, metformin, antidiabetic mechanism, signaling pathways, hepatic gene expression
- MeSH terms
- Animals, Berberine, Blood Glucose, Body Weight, Computer Simulation, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, DNA-Binding Proteins, Gene Expression Regulation, Hypoglycemic Agents, Mice, Inbred C57BL, Receptors, Glucocorticoid, Computational Biology, Mice, KCNQ1 Potassium Channel, Gene Regulatory Networks
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