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白藜芦醇作为治疗肌少症性肥胖的潜在治疗剂:来自体内实验的见解。

Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments.

机构信息

Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.

Key Laboratory of Mitochondrial Medicine, Key Laboratory of Genetic and Developmental Related Diseases, School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China.

出版信息

Biomed Pharmacother. 2024 Oct;179:117396. doi: 10.1016/j.biopha.2024.117396. Epub 2024 Sep 4.

Abstract

Sarcopenic obesity (SO) is a metabolic disorder with increasing prevalence. It is characterized by a reduction in skeletal muscle mass and strength. Resveratrol (RSV) is one of the most frequently used herbs in the treatment of skeletal muscle atrophy. However, the precise mechanism of the action of RSV in SO remains unclear. The objective of this study was to examine the pharmacological mechanism of RSV in the context of SO through the lens of network pharmacology, to validate these findings through in vivo experimentation. A list of potential RSV targets was compiled by retrieving the data from multiple databases. This list was then cross-referenced with a list of potential targets related to SO. The intersections of RSV- and SO-related targets were analyzed using Venn diagrams. To identify the core genes, a protein-protein interaction (PPI) network of the intersection targets was constructed and subsequently analyzed. Molecular docking was used to predict RSV binding to its core targets. A high-fat diet was used to induce SO in mice. These findings indicated that RSV may prevent SO by acting on 11 targets. Among these, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF) are considered core targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the anti-SO effect of RSV was predominantly linked to metabolic disease-related pathways, including those associated with nonalcoholic fatty liver disease. The anti-inflammatory effects of RSV were confirmed in vivo in an SO mouse model. This study contributes to a more comprehensive understanding of the key mechanisms of the action of RSV against SO and provides new possibilities for drug development in the pathological process of SO.

摘要

肌少症性肥胖(SO)是一种患病率不断增加的代谢紊乱。其特征是骨骼肌质量和力量下降。白藜芦醇(RSV)是治疗骨骼肌萎缩最常用的草药之一。然而,RSV 在 SO 中的作用的确切机制尚不清楚。本研究旨在通过网络药理学的角度研究 RSV 在 SO 中的药理机制,并通过体内实验验证这些发现。通过从多个数据库中检索数据,编制了 RSV 潜在靶点列表。然后将该列表与与 SO 相关的潜在靶点列表进行交叉引用。使用 Venn 图分析 RSV-和 SO 相关靶点的交集。为了确定核心基因,构建了交集靶点的蛋白质-蛋白质相互作用(PPI)网络,并对其进行了分析。使用分子对接预测 RSV 与核心靶标的结合。使用高脂肪饮食诱导小鼠发生 SO。研究结果表明,RSV 可能通过作用于 11 个靶点来预防 SO。其中,白细胞介素 6(IL-6)、C 反应蛋白(CRP)和肿瘤坏死因子(TNF)被认为是核心靶点。京都基因与基因组百科全书(KEGG)富集结果表明,RSV 对 SO 的抗作用主要与代谢性疾病相关途径有关,包括与非酒精性脂肪性肝病相关的途径。在 SO 小鼠模型中体内证实了 RSV 的抗炎作用。本研究有助于更全面地了解 RSV 针对 SO 的作用的关键机制,并为 SO 病理过程中的药物开发提供了新的可能性。

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