基于UHPLC-QE-MS技术和网络药理学研究四妙散治疗膝骨关节的药效物质基础及作用机制

Material Basis and Mechanism of Simiao San(四妙散)in Treatment of Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking

目的:分析并鉴定四妙散的化学成分和入血成分,预测其治疗膝骨关节炎(KOA)的药效物质基础和作用机制。方法:采用超高效液相色谱-四级杆-静电场轨道阱质谱联用(UHPLC-QE-MS)技术鉴定四妙散的化学成分及入血成分。根据入血成分进行网络药理学分析,并对核心成分和关键靶点进行分子对接验证。结果:从四妙散水煎剂中共鉴定出354个化学成分。通过比较四妙散水煎剂、空白血清及含药血清样本数据,鉴定出21个入血成分,主要包括黄酮类、萜类、苯丙素类、生物碱类等成分。网络药理学结果表明,四妙散入血成分可能通过调节AKT1、ALB、TNF、EGFR、JUN、SRC、MAPK3等关键靶点,调控PI3K/AKT、Ras、TNF等信号通路发挥治疗KOA效应。分子对接结果显示,四妙散核心入血成分与关键靶点之间具有较好的结合活性。结论:四妙散中黄酮类等入血成分可能通过作用于AKT1等关键靶点,调控PI3K/AKT等关键通路进而发挥治疗KOA效应。

Objective:To systematically analyze and identify the chemical and blood-entry components of Simiao San,predicting its material basis and mechanism in the treatment of knee osteoarthritis(KOA).Method:The chemical and blood-entry components of Simiao San were identified using ultra-high performance liquid chromatography coupled with Q Exactive mass spectrometry(UHPLC-QE-MS).Based on these blood-entry components,network pharmacological analyses were conducted,followed by molecular docking validation of the core components and key targets.Result:A total of 354 chemical components were identified in the water decoction of Simiao San.Comparative analysis of the water decoction,blank serum,and drug-containing serum samples led to the preliminary identification of 21 blood-entry components,predominantly flavonoids,terpenoids,phenylpropanoids,alkaloids,and other compounds.Network pharmacology results indicated that the blood-entry components of Simiao San may exert anti-KOA effects by targeting key proteins such as AKT1,ALB,TNF,EGFR,JUN,SRC,and MAPK3,and modulating pathways including PI3K-AKT,Ras,and TNF.Molecular docking results demonstrated strong binding activity between the core blood-entry components and key targets.Conclusion:The flavonoids and other blood-entry components of Simiao San may exert anti-KOA effects by acting on key targets such as AKT1 and regulating critical pathways like the PI3K-AKT pathway.