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
王杰 1王金梅 2刘慧 2刘旭光 3郭文静 3何红平4
作者信息
- 1. 云南中医药大学,云南 昆明 650500;河南大学 国家食用菌加工技术研发专业中心,河南 开封 475004
- 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;河南大学农学院,河南 开封 475004
- 3. 河南大学 国家食用菌加工技术研发专业中心,河南 开封 475004
- 4. 云南中医药大学,云南 昆明 650500
- 折叠
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.
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.
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Key words
Agaricus bisporus/hepatoprotection/network pharmacology/ultra-high performance liquid chromatography-tandem mass spectrometry/mechanism of action引用本文复制引用
出版年
2025
国家科技期刊平台
NSTL
万方数据