Faculty of Basic Medicine, Guilin Medical University, Guilin, PR China.
Cardiology Department Area 1, Guigang City People's Hospital, the Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi, PR China.
Bioengineered. 2021 Dec;12(1):4757-4767. doi: 10.1080/21655979.2021.1954581.
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 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.
二甲双胍是一种常用于治疗糖尿病的临床药物，越来越多的证据表明它具有潜在的抗肥胖作用。然而，二甲双胍与肥胖相关高血压相关的详细机制仍未被揭示。我们已经利用生物信息学策略，包括网络药理学和分子对接分析，来揭示针对癌症、2019 年冠状病毒病等临床疾病的生物活性化合物的药理学靶点和分子途径。在本报告中，我们利用网络药理学和分子对接的方法来鉴定二甲双胍治疗肥胖相关高血压的核心靶点、药理学功能和机制。网络分析确定了肥胖和高血压的 154 个差异表达基因，以及 21 个相互作用基因、6 个二甲双胍治疗肥胖相关高血压的核心基因。结果表明，分子对接结果表明二甲双胍与肥胖和高血压相关组织中表达的关键蛋白（包括白细胞介素 6（IL-6）和趋化因子（C-C 基序）配体 2（CCL2））具有结合能力。二甲双胍发挥降压/减肥作用涉及代谢调节、炎症抑制。揭示了二甲双胍的降压/减肥机制，包括调节炎症和免疫信号通路，以改善靶向组织的微环境稳态。总之，我们当前的生物信息学研究结果揭示了二甲双胍治疗肥胖相关高血压的所有药理学靶点、生物学功能和信号通路，从而促进了其在未来的临床应用。
