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基于整合网络分析和代谢组学探讨吴茱萸汤治疗酒精性胃溃疡的作用机制

Mechanism of Wuzhuyu decoction on alcohol-induced gastric ulcers using integrated network analysis and metabolomics.

作者信息

Wang Xin, Chen Lisheng, Chang Lei, He Yong, He Tingting, Wang Ruilin, Wei Shizhang, Jing Manyi, Zhou Xuelin, Li Haotian, Zhao Yanling

机构信息

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Department of Pharmacy Department, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

出版信息

Front Pharmacol. 2024 Jan 8;14:1308995. doi: 10.3389/fphar.2023.1308995. eCollection 2023.

Abstract

Gastric ulcers (GUs) are prevalent digestive disorders worldwide. Wuzhuyu Decoction (WZYT) is a traditional Chinese medicine that has been employed for centuries to alleviate digestive ailments like indigestion and vomiting. This study aims to explore the potential effects and underlying mechanisms of WZYT on alcohol induced gastric ulcer treatment. We employed macroscopic assessment to evaluate the gastric ulcer index (UI), while the enzyme-linked immunosorbent assay (ELISA) was utilized for detecting biochemical indicators. Pathological tissue analysis involved hematoxylin-eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining to assess gastric tissue damage. Additionally, the integration of network analysis and metabolomics facilitated the prediction of potential targets. Validation was conducted using Western blotting. The research revealed that WZYT treatment significantly reduced the gastric ulcer index (UI) and regulation of alcohol-induced biochemical indicators levels. Additionally, improvements were observed in pathological tissue. Network analysis results indicated that 62 compounds contained in WZYT modulate alcohol-induced gastric ulcers by regulating 183 genes. The serum metabolomics indicated significant changes in the content of 19 metabolites after WZYT treatment. Two pivotal targets, heme oxygenase 1 (HMOX1) and albumin (ALB), are believed to assume a significant role in the treatment of gastric ulcers by the construction of "compounds-target-metabolite" networks. Western blot analysis confirmed that WZYT has the capacity to elevate the expression of HMOX1 and ALB targets. The integration of network analysis and metabolomics provides a scientific basis to propel the clinical use of WZYT for GUs. Our study provides a theoretical basis for the use of Wuzhuyu decoction in the treatment of gastric ulcers.

摘要

胃溃疡(GUs)是全球普遍存在的消化系统疾病。吴茱萸汤(WZYT)是一种传统中药,数百年以来一直用于缓解消化不良和呕吐等消化系统疾病。本研究旨在探讨吴茱萸汤对酒精性胃溃疡治疗的潜在作用及潜在机制。我们采用宏观评估来评价胃溃疡指数(UI),同时利用酶联免疫吸附测定(ELISA)检测生化指标。病理组织分析包括苏木精-伊红(H&E)染色和过碘酸-希夫(PAS)染色,以评估胃组织损伤。此外,网络分析与代谢组学相结合有助于预测潜在靶点。通过蛋白质印迹法进行验证。研究发现,吴茱萸汤治疗可显著降低胃溃疡指数(UI),并调节酒精诱导的生化指标水平。此外,病理组织也有改善。网络分析结果表明,吴茱萸汤中的62种化合物通过调节183个基因来调节酒精诱导的胃溃疡。血清代谢组学表明,吴茱萸汤治疗后19种代谢物的含量发生了显著变化。通过构建“化合物-靶点-代谢物”网络,认为两个关键靶点血红素加氧酶1(HMOX1)和白蛋白(ALB)在胃溃疡治疗中起重要作用。蛋白质印迹分析证实,吴茱萸汤有能力提高HMOX1和ALB靶点的表达。网络分析与代谢组学的结合为推动吴茱萸汤在胃溃疡临床应用方面提供了科学依据。我们的研究为吴茱萸汤治疗胃溃疡的应用提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c8/10800891/695493698ac7/fphar-14-1308995-g001.jpg

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