中医药信息2025,Vol.42Issue(11):26-36,11.DOI:10.19656/j.cnki.1002-2406.20251105
基于HPLC-QTOF-MS结合网络药理学分析苦地丁抗急性肝损伤的体内化学成分及其作用机制
Analysis of the In Vivo Chemical Components and Mechanism of Corydalis Bungeanae Herba against Acute Liver Injury Based on HPLC-QTOF-MS Combined with Network Pharmacology
摘要
Abstract
Objective:To reveal the pharmacodynamic material basis and mechanism of Corydalis Bungeanae Herba in improving lipopolysaccharide/D-galactosamine(LPS/D-GalN)-induced acute liver injury in mice based on high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(HPLC-QTOF-MS)combined with network pharmacology and validation experiments.Methods:Eight-week-old male BALB/c mice were randomly divided into a blank group,a background group,a model group,a positive drug group,and low-,medium-,and high-dose Corydalis Bungeanae Herba groups,with 7 mice in each group.The blank group and the model group were administered an equal volume of 0.9% normal saline daily by gavage;the low-,medium-,and high-dose Corydalis Bungeanae Herba groups were administered Corydalis Bungeanae Herba extract at doses of 0.5 g/kg,1 g/kg,and 2 g/kg by gavage respectively;the positive drug group was administered 200 mg/kg biphenyl dimethyl dicarboxylate;the background group was administered 2 g/kg Corydalis Bungeanae Herba extract by gavage.All groups were administered for 10 consecutive days.One hour after the last administration on the 10th day,the model group,the low-,medium-,and high-dose Corydalis Bungeanae Herba groups,and the positive drug group were intraperitoneally injected with a mixed solution of LPS(50 μg/kg)and D-GalN(500 mg/kg);the blank group and the background group were intraperitoneally injected with an equal volume of 0.9% normal saline respectively.Serum ALT and AST levels were measured,and liver HE staining was observed.HPLC-QTOF-MS technology was used to identify the blood-absorbed and liver-distributed chemical components of Corydalis Bungeanae Herba.Network pharmacology was applied to predict the action pathways,and molecular docking technology was used to validate the target pathways activated by the primary chemical components of Corydalis Bungeanae Herba.Oxidative stress-related indicators(MPO,MDA,GSH-Px)in liver tissue,inflammatory indicators(TNF-α,IL-1β)in serum and liver,and TUNEL staining were detected.Western blot technology was used to validate the pathways through which Corydalis Bungeanae Herba extract exerts its effects.Results:Corydalis Bungeanae Herba significantly reduced the serum ALT and AST levels and the expression of inflammatory factors TNF-α and IL-1β in serum and liver in mice with acute liver injury,decreased liver MPO and MDA levels,increased the level of the antioxidant enzyme GSH-Px,and alleviated liver injury.HPLC-QTOF-MS technology identified a total of 19 blood-absorbed chemical components and 17 liver-distributed chemical components.Based on network pharmacology technology,it was predicted that the Corydalis Bungeanae Herba extract exerts its pharmacological effects mainly through the PI3K/Akt signaling pathway.Further validation experiments found that the Corydalis Bungeanae Herba extract can inhibit the PI3K/Akt signaling pathway to exert an anti-hepatocyte apoptosis effect.Conclusion:Corydalis Bungeanae Herba exerts anti-inflammatory,antioxidant stress,and anti-hepatocyte apoptosis effects by regulating the PI3K/Akt signaling pathway.关键词
苦地丁/急性肝损伤/高效液相色谱-四极杆飞行时间质谱/网络药理学/PI3K/Akt信号通路Key words
Corydalis Bungeanae Herba/Acute liver injury/HPLC-QTOF-MS/Network pharmacology/PI3K/Akt signaling pathway引用本文复制引用
肖琪,付俊,李木子,张振旭,崔国倩,武洁,李钦宁,朱粉霞..基于HPLC-QTOF-MS结合网络药理学分析苦地丁抗急性肝损伤的体内化学成分及其作用机制[J].中医药信息,2025,42(11):26-36,11.基金项目
国家自然科学基金项目(81473430) (81473430)
江苏省医学创新团队项目(CXTDB2017003) (CXTDB2017003)