Untargeted metabolomic analysis of the therapeutic effects of Pholiota adiposa in H22 hepatocellular carcinoma tumor-bearing mice

文献类型： 外文期刊

第一作者： Wang, Xiao-yan

作者： Wang, Xiao-yan;Dai, Le;Liu, Yan;Li, Gang

作者机构：

关键词： Pholiota adiposa; Antitumor activity; Pharmacological mechanism; Serum metabonomic; UPLC-ESI-QTOF/MS

期刊名称：JOURNAL OF BIOENERGETICS AND BIOMEMBRANES （ 影响因子：3.0； 五年影响因子：3.0 ）

ISSN： 0145-479X

年卷期： 2025 年

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收录情况： SCI

摘要： Pholiota adiposa is a traditional Chinese medicine "Huangsan". Huangsan is rich in proteins, polysaccharides, which has been documented to be used in the treatment of cancer. However, the pharmacological mechanism of Huangsan in the treatment of cancer remains unclear. This research examined the anticancer mechanisms of the ethanol extract of P. adiposa (EPA) in hepatoma-bearing mice via metabolomic analysis. Male ICR mice were randomly assigned to the control (CG), model (MG), positive (25 mg/kg/day cyclophosphamide; PG), low-level EPA (LG, 100 mg/kg/day), and high-level EPA (HG, 300 mg/kg/day) groups. Various biochemical indicators were assessed via enzyme-linked immunosorbent assay, TdT-mediated dUTP nick-end labeling assay, and hematoxylin and eosin staining. Western blot was utilized to assess tumor apoptosis-related caspase-3, cleaved caspase-3, Bcl-2, Bcl-2-associated X, and vascular endothelial growth factor. Ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry and chemometric approaches were applied to determine serum metabolomics. EPA substantially impacted tumor growth in vivo without causing adverse reactions, indicating liver and kidney protection. EPA significantly increased the levels of glutamine, leucine, histidine, citrulline, creatine, prostaglandin A2, and prostaglandin D2 while decreasing levels of arachidonic acid, 20-hydroxyeicosatetraenoic acid, thromboxane B2, and pyruvate. These changes reflected a reduction in protein digestion and absorption, alterations in gamma-aminobutyric acid metabolism, and shifts in amino acid metabolism, particularly affecting arachidonic acid, arginine, and proline. EPA exerted significant anticancer effects in mice mainly by reducing the compensatory energy supply from branched-chain amino acids, regulating amino acid metabolism, inhibiting negative nitrogen balance, enhancing immune responses, inhibiting inflammatory mediators, and promoting tumor cell apoptosis in the tumor microenvironment.

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