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Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Correlational Analysis of Liver Metabolites and Pharmacodynamic Indexes in Xanthoxylin-Treated Acute Liver Failure
Fengfeng Xie1, Huimin Luo1, Yuchen Shen1
1Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China.
Abstract:
Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-κB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), NF-κB, Inhibitor of NF-κB α (IκBα), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the IκBα/NF-κB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism.
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