Wang Xiao-Yan, Dai Le, Liu Yan, Li Gang
Academy of Traditional Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin, 132109, China.
Academy of Medical, Changchun Sci-Tech University, Changchun, 130600, P. R. China.
J Bioenerg Biomembr. 2025 Aug 7. doi: 10.1007/s10863-025-10070-1.
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 γ-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.
黄伞是一种传统中药“黄蘑”。黄蘑富含蛋白质、多糖，已被记载可用于治疗癌症。然而，黄蘑治疗癌症的药理机制仍不清楚。本研究通过代谢组学分析研究了黄伞乙醇提取物（EPA）对荷肝癌小鼠的抗癌机制。雄性ICR小鼠被随机分为对照组（CG）、模型组（MG）、阳性组（25 mg/kg/天环磷酰胺；PG）、低剂量EPA组（LG，100 mg/kg/天）和高剂量EPA组（HG，300 mg/kg/天）。通过酶联免疫吸附测定、TdT介导的dUTP缺口末端标记测定和苏木精-伊红染色评估各种生化指标。利用蛋白质免疫印迹法评估肿瘤凋亡相关的半胱天冬酶-3、裂解的半胱天冬酶-3、Bcl-2、Bcl-2相关X蛋白和血管内皮生长因子。应用超高效液相色谱-电喷雾电离四极杆飞行时间质谱和化学计量学方法测定血清代谢组学。EPA对体内肿瘤生长有显著影响且无不良反应，表明对肝肾有保护作用。EPA显著增加了谷氨酰胺、亮氨酸、组氨酸、瓜氨酸、肌酸、前列腺素A2和前列腺素D2的水平，同时降低了花生四烯酸、20-羟基二十碳四烯酸、血栓素B2和丙酮酸的水平。这些变化反映了蛋白质消化吸收减少、γ-氨基丁酸代谢改变以及氨基酸代谢变化，尤其影响花生四烯酸、精氨酸和脯氨酸。EPA在小鼠中发挥显著抗癌作用主要是通过减少支链氨基酸的代偿性能量供应、调节氨基酸代谢、抑制负氮平衡、增强免疫反应、抑制炎症介质以及促进肿瘤微环境中的肿瘤细胞凋亡。
