基于网络药理学探究双孢菇的肝脏保护作用

doi:10.7506/spkx1002-6630-20240614-096

食品科学 ›› 2025, Vol. 46 ›› Issue (2): 126-137.doi: 10.7506/spkx1002-6630-20240614-096

基于网络药理学探究双孢菇的肝脏保护作用

王杰，王金梅，刘慧，刘旭光，郭文静，何红平

（1.云南中医药大学，云南昆明 650500；2.河南大学国家食用菌加工技术研发专业中心，河南开封 475004；3.河南大学农学院，河南开封 475004）

出版日期:2025-01-25 发布日期:2024-12-30
基金资助:
中央引导地方科技发展资金项目（Z20231811055）

Exploring the Hepatoprotective Effect of Agaricus bisporus Based on Network Pharmacology

WANG Jie, WANG Jinmei, LIU Hui, LIU Xuguang, GUO Wenjing, HE Hongping

(1. Yunnan University of Chinese Medicine, Kunming 650500, China; 2. National R&D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China; 3. College of Agriculture, Henan University, Kaifeng 475004, China)

Online:2025-01-25 Published:2024-12-30

摘要/Abstract

摘要： 为研究双孢菇乙醇提取物（Agaricus bisporus ethanol extract，ABEE）保肝活性的物质基础及其作用机制，采用超高效液相色谱-串联质谱（ultra-high performance liquid chromatography-tandem mass spectrometry，UPLC-MS/MS）技术对ABEE的成分进行分析鉴定，通过网络药理学结合CCl4致小鼠急性肝损伤动物模型对其活性物质及作用机制进行分析。UPLC-MS/MS分析鉴定化合物75 个，其中网络药理学预测与肝损伤活性相关化合物15 个，作用靶点11 个。动物实验结果显示，ABEE能够显著改善由CCl4导致的小鼠急性肝损伤，与模型组相比，高剂量组（1 000 mg/kg）肝功能指标谷草转氨酶、谷丙转氨酶、碱性磷酸酶得到了显著恢复（P＜0.001），同时小鼠体内抗氧化能力得到显著提高，与模型组相比，超氧化物歧化酶、谷胱甘肽过氧化物酶活力显著提高（P＜0.001），丙二醛含量显著下降（P＜0.01）。采用实时荧光定量聚合酶链式反应和Western blot技术对相关基因的mRNA和蛋白表达水平进行检测，结果显示，与模型组相比，高剂量组Bcl-2表达显著上升（P＜0.001），MYC、NF-κB1、RELA、MMP9表达显著降低（P＜0.01），证实了预测结果。因此，ABEE可能是通过水杨酸、棕榈酸、α-亚麻酸、白杨素调节Bcl-2、MYC、NF-κB1、RELA的表达及其所在的化学致癌-受体激活等信号通路，从而发挥肝脏保护作用。本研究结果表明ABEE可能是通过多成分、多靶点、多通路抑制细胞凋亡、癌变，抑制自由基脂质过氧化来发挥肝脏保护作用。

关键词: 双孢菇；肝脏保护；网络药理学；超高效液相色谱-串联质谱联用；作用机制

Abstract: To investigate the hepatoprotective components and mechanism of Agaricus bisporus ethanol extract (ABEE), ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze and identify the components of ABEE. The active components and mechanism were analyzed using network pharmacology and a mouse model of CCl4-induced acute liver injury. UPLC-MS/MS analysis identified 75 compounds, of which 15 were predicted by network pharmacology to be related to liver injury, with 11 different targets. Animal experiments showed that ABEE significantly alleviated CCl4-induced acute liver injury in mice. Compared with the model group, the high-dose group (1 000 mg/kg) showed significant recovery in liver function indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AKP) (P < 0.001). The antioxidant capacity in mice was significantly enhanced, as evidenced by a significant increase in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P < 0.001) and a significant decrease in malondialdehyde (MDA) content (P < 0.01). Detection of the mRNA and protein expression levels of relevant genes was performed using real-time quantitative polymerase chain reaction (PCR) and Western blot techniques, showing that compared with the model group, the expression of the Bcl-2 in the high-dose group significantly increased (P < 0.001), while the expression of MYC, NF-κB1, RELA and MMP9 significantly decreased (P < 0.01). These results confirmed the predictions, indicating that ABEE might exert its hepatoprotective effect by regulating the expression of Bcl-2, MYC, NF-κB1 and RELA through salicylic acid, palmitic acid, linolenic acid, and chrysin, as well as their associated signaling pathways such as chemical carcinogenesis-receptor activation. This study suggests that ABEE may provide liver protection by inhibiting apoptosis, carcinogenesis, and lipid peroxidation caused by free radicals through multiple components, targets, and pathways.

Key words: Agaricus bisporus; hepatoprotection; network pharmacology; ultra-high performance liquid chromatography-tandem mass spectrometry; mechanism of action

中图分类号:

TS201.4

王杰，王金梅，刘慧，刘旭光，郭文静，何红平. 基于网络药理学探究双孢菇的肝脏保护作用[J]. 食品科学, 2025, 46(2): 126-137 https://doi.org/10.7506/spkx1002-6630-20240614-096

WANG Jie, WANG Jinmei, LIU Hui, LIU Xuguang, GUO Wenjing, HE Hongping. Exploring the Hepatoprotective Effect of Agaricus bisporus Based on Network Pharmacology[J]. FOOD SCIENCE, 2025, 46(2): 126-137 https://doi.org/10.7506/spkx1002-6630-20240614-096

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基于网络药理学探究双孢菇的肝脏保护作用

Exploring the Hepatoprotective Effect of Agaricus bisporus Based on Network Pharmacology

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