Uncovering antiobesity-related hypertension targets and mechanisms of metformin, an antidiabetic medication

Metformin, a common clinical drug used to treat diabetes mellitus, is found with potential antiobese actions as reported in increasing evidences. However, the detailed mechanisms of metformin-antiobesity-related hypertension remain unrevealed. We have utilized the bioinformatics strategy, including network pharmacology and molecular docking analyses, to uncover pharmacological targets and molecular pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease 2019. In this report, the in-silico approaches using network pharmacology and molecular docking was utilized to identify the core targets, pharmacological functions and mechanisms of metformin against obesity-related hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, and 21 interaction genes, 6 core genes of metformin treating obesity-related hypertension. As results, molecular docking findings indicated the binding capability of metformin with key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2) expressed in obesity- and hypertension-dependent tissues. Metformin-exerted antihypertension/obesity actions involved in metabolic regulation, inflammatory suppression. And antihypertension/obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for ameliorating microenvironmental homeostasis in targeting tissues. In conclusion, our current bioinformatics findings have uncovered all pharmacological targets, biological functions and signaling pathways of metformin treating obesity-related hypertension, thus promoting its clinical application in future.

二甲双胍（Metformin）是一种常用于治疗糖尿病的临床药物，越来越多的研究证据表明其具有潜在的抗肥胖作用。然而，二甲双胍抗肥胖相关性高血压的具体作用机制仍未阐明。本研究采用生物信息学策略，包括网络药理学（network pharmacology）与分子对接（molecular docking）分析，用以揭示针对癌症、2019冠状病毒病等临床疾病的生物活性化合物的药理学靶点与分子通路。本研究通过网络药理学与分子对接的计算机模拟（in-silico）方法，旨在鉴定二甲双胍对抗肥胖相关性高血压的核心靶点、药理学功能及作用机制。网络分析共筛选出肥胖与高血压相关的154个差异表达基因、21个互作基因，以及二甲双胍治疗肥胖相关性高血压的6个核心基因。分子对接结果显示，二甲双胍可与肥胖及高血压相关组织中表达的关键蛋白结合，包括白细胞介素6（IL-6）与趋化因子C-C基序配体2（CCL2）。二甲双胍发挥的抗高血压与抗肥胖作用涉及代谢调控与炎症抑制过程。本研究还阐明了二甲双胍的抗高血压与抗肥胖机制，包括通过调控炎症与免疫信号通路，改善靶组织的微环境稳态。综上，本研究通过生物信息学分析阐明了二甲双胍治疗肥胖相关性高血压的全部药理学靶点、生物学功能及信号通路，为其未来的临床应用奠定了理论基础。