School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Pharmacy, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
Department of China Military Institute of Chinese Materia, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
Biomed Pharmacother. 2021 Jun;138:111490. doi: 10.1016/j.biopha.2021.111490. Epub 2021 Mar 24.
This study was aimed to explore the mechanism of rutaecarpine (RUT) on ethanol-induced gastric ulcer (GU) in mice by integrated approaches. At first, the efficacy was determined through the macroscopic and microscopic state of stomach tissue and the expression levels of GU-related factors. Then, the serum metabolomics method based on UPLC-Q-TOF/MS was used to explore the specific metabolites and metabolic pathways. Finally, the upstream key protein targets of these specific metabolites were analyzed by network pharmacology and verified by PCR to explore the potential mechanism. RUT alleviated the histological and pathological damage of gastric tissue caused by ethanol, and could remarkably ameliorate the level of GU-related factors. Subsequently, a total of 7 potential metabolites involved in 9 metabolic pathways were identified by metabolomics analysis. Then, a 'component-targets-metabolites' interaction network was constructed, and therefore 4 key target proteins (PLA2G1B, PDE5A, MIF and SRC) that may regulate the specific metabolites were obtained. This case was further verified by the results of PCR. ALL the above results strongly demonstrated that RUT exerted a gastroprotective effect against GU. And it is the first time to combine metabolomics combined with network pharmacology to elucidate the mechanism of RUT on GU, which may be related to the regulation of energy metabolism, oxidative stress, and inflammation, and these pathways may be regulated through the upstream protein PLA2G1B, PDE5A, MIF and SRC.
本研究旨在采用整合方法探讨吴茱萸碱（RUT）对乙醇诱导的小鼠胃溃疡（GU）的作用机制。首先，通过胃组织的宏观和微观状态以及与 GU 相关的因子表达水平来确定功效。然后，采用基于 UPLC-Q-TOF/MS 的血清代谢组学方法来探索特定的代谢物和代谢途径。最后，通过网络药理学分析和 PCR 验证来分析这些特定代谢物的上游关键蛋白靶标，以探讨潜在的机制。RUT 减轻了乙醇引起的胃组织的组织学和病理学损伤，能显著改善 GU 相关因子的水平。随后，通过代谢组学分析鉴定出 7 种涉及 9 种代谢途径的潜在代谢物。然后，构建了“成分-靶标-代谢物”相互作用网络，从而获得了 4 个可能调节特定代谢物的关键靶蛋白（PLA2G1B、PDE5A、MIF 和 SRC）。这一案例进一步通过 PCR 的结果得到了验证。所有这些结果都有力地证明了 RUT 对 GU 具有胃保护作用。这是首次结合代谢组学和网络药理学来阐明 RUT 对 GU 的作用机制，其可能与能量代谢、氧化应激和炎症的调节有关，这些途径可能通过上游蛋白 PLA2G1B、PDE5A、MIF 和 SRC 来调节。
