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02.07.2021 | Original Contribution

Multi-omics integration reveals the hepatoprotective mechanisms of ursolic acid intake against chronic alcohol consumption

verfasst von: Xin Yan, Xiaoyun Liu, Yu Wang, Xueyang Ren, Jiamu Ma, Ruolan Song, Xiuhuan Wang, Ying Dong, Qiqi Fan, Jing Wei, Axiang Yu, Hong Sui, Gaimei She

Erschienen in: European Journal of Nutrition | Ausgabe 1/2022

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Abstract

Purpose

Alcoholic liver disease (ALD) is a major health issue globally. In addition to pharmacotherapy, dietary support is also regarded as reliable strategy for ALD management. As a widely distributed natural constituent within edible plants, the present study aims to investigate the hepatoprotective effects of ursolic acid (UA) against ALD and also to deepen insights into the underlying targets and mechanisms comprehensively.

Methods

The hepatoprotective activity of UA against chronic alcohol-induced liver injury was investigated on Lieber–DeCarli liquid diet-based mouse model. In-depth RNA-seq transcriptomics and TMT-based proteomics analyses were conducted in parallel. Data integration as well as bioinformatics analysis were also performed to unravel the targets and mechanisms associated with the hepatoprotective activity of UA intake against alcoholic liver injury comprehensively.

Results

The serum biomarkers and pathological characteristics indicated the hepatoprotective effects of UA intake on alcoholic liver injury. 567 target genes and 377 target proteins related to the hepatoprotective activity of UA were identified in transcriptomics and proteomics analysis respectively, most of which were associated with function of cellular process, cell part and binding. After data integration, 56 co-regulated targets, including ADH4, CYP450 enzymes, NQO1, apolipoproteins, glutathione–S–transferase, etc. which were consistently modulated on both mRNA and protein levels were identified. These co-regulated targets were found to be correlated with 70 KEGG pathways led by carcinogenesis, retinol metabolism and CYP450 metabolism pathways.

Conclusion

UA intake ameliorated chronic alcohol-induced liver injury. Given the role of the co-regulated targets in ALD and the bioinformatics analysis results, CYP450-, glutathione and redox homeostasis-dependent antioxidation, promotion of lipid transport, and restoration of ethanol metabolic capacity are the potentially underlying mechanisms. This information will further deepen our insights into the hepatoprotective effects of UA-rich edible plants, and provide us valuable instruction for ALD management.

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Titel: Multi-omics integration reveals the hepatoprotective mechanisms of ursolic acid intake against chronic alcohol consumption
verfasst von: Xin Yan
Xiaoyun Liu
Yu Wang
Xueyang Ren
Jiamu Ma
Ruolan Song
Xiuhuan Wang
Ying Dong
Qiqi Fan
Jing Wei
Axiang Yu
Hong Sui
Gaimei She
Publikationsdatum: 02.07.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 1/2022
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-021-02632-x

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