目的 通过对豨莶草化学成分鉴定，结合网络药理学和细胞实验验证，探讨豨莶草治疗心肌缺氧损伤的药效成分和潜在的作用机制。方法 采用超高效液相色谱-离子阱-静电场轨道肼质谱（ UHPLC-LTQ-Orbitrap MS）技术对豨莶草醇提物的化学成分进行鉴定，以鉴定出来的化学成分为研究对象，采用网络药理学方法筛选豨莶草对心肌缺氧损伤具有保护作用的活性成分并预测治疗靶点。基于H9c2心肌细胞缺氧损伤模型，验证豨莶草代表性活性成分豨莶精醇和奇壬醇的关键通路和靶点。结果 豨莶草醇提液共鉴定出43个化学成分，筛选豨莶精醇和奇壬醇可能是豨莶草治疗心肌缺氧损伤的关键活性成分，STAT3、SHBG、IL2、CYP19A1、HMGCR、PTPN1和AR可能是关键靶点。豨莶精醇和奇壬醇能够提高H9c2细胞缺氧损伤模型超氧化物歧化酶（ SOD）的活性，降低乳酸脱氢酶（ LDH）、活性氧（ ROS）和丙二醛（ MDA）水平。豨莶精醇和奇壬醇上调了磷酸化Janus激酶2/Janus激酶2（ p-JAK2/JAK2）和磷酸化信号转导及转录激活蛋白3/信号转导及转录激活蛋白3（p-STAT3/STAT3）的值，降低了Bcl-2相关X蛋白/B淋巴细胞瘤-2（Bax/Bcl-2）值，下调了半胱天冬酶-9（Caspase-9）和半胱天冬酶-3（ Caspase-3 ）的表达。结论 筛选获得豨莶草活性成分豨莶精醇和奇壬醇，可通过激活JAK2/STAT3信号通路抑制氧化应激和减少细胞凋亡，发挥抗心肌缺氧损伤作用。

Objective To explore the pharmacological components and potential mechanisms of Siegesbeckiae Herba in treating myocardial hypoxia injury by combining chemical component identification with network pharmacology and cell experiments. Methods Ultra high performance liquid chromatography ion trap electrostatic field orbital hydrazine mass spectrometry (UHPLCLTQ Orbitrap MS) technology was used to identify the chemical components of the alcohol extract of Siegesbeckiae Herba. The identified chemical components were used as the research object, and network pharmacology was used to screen the active ingredients of Siegesbeckiae Herba that have protective effects on myocardial hypoxia injury and predict therapeutic targets. Key pathways and targets were validated through the treatment of H9c2 myocardial cell hypoxia injury model with darutigenol and kirenol, which are representative active ingredients of Siegesbeckiae Herba. Results A total of 43 chemical components were identified in Siegesbeckiae Herba. Among them, darutigenol and kirenol may be the active ingredients in Siegesbeckiae Herba for treating myocardial hypoxia injury, while STAT3, SHBG, IL2, CYP19A1, HMGCR, PTPN1, and AR may be key targets. Darutigenol and kirenol could elevate the activity of antioxidant enzymes SOD, reduced LDH, ROS, and MDA levels in hypoxia-exposed H9c2 cells. Moreover, darutigenol and kirenol upregulated the expression of p-JAK2/JAK2 and p-STAT3/STAT3, reduced Bax/Bcl-2 ratio and the expression of Caspase-9 and Caspase-3. Conclusion Siegesbeckiae Herba and its active ingredients can enhance antioxidant and anti apoptotic abilities by activating the JAK2/STAT3 signaling pathway, exerting anti myocardial hypoxia injury effects.

R285.5

北京中医药大学东直门医院2023年度科技创新专项（DZMKJCX-2023-025）；北京中医药大学2022年度基本科研业务费（2022-JYB-SYS-005）；北京中医药大学重点实验室项目（1000061222482）