目的 通過對豨薟草化學成分鑒定，結合網(wǎng)絡藥理學和細胞實驗驗證，探討豨薟草治療心肌缺氧損傷的藥效成分和潛在的作用機制。方法 采用超高效液相色譜-離子阱-靜電場軌道肼質(zhì)譜（ UHPLC-LTQ-Orbitrap MS）技術對豨薟草醇提物的化學成分進行鑒定，以鑒定出來的化學成分為研究對象，采用網(wǎng)絡藥理學方法篩選豨薟草對心肌缺氧損傷具有保護作用的活性成分并預測治療靶點?；贖9c2心肌細胞缺氧損傷模型，驗證豨薟草代表性活性成分豨薟精醇和奇壬醇的關鍵通路和靶點。結果 豨薟草醇提液共鑒定出43個化學成分，篩選豨薟精醇和奇壬醇可能是豨薟草治療心肌缺氧損傷的關鍵活性成分，STAT3、SHBG、IL2、CYP19A1、HMGCR、PTPN1和AR可能是關鍵靶點。豨薟精醇和奇壬醇能夠提高H9c2細胞缺氧損傷模型超氧化物歧化酶（ SOD）的活性，降低乳酸脫氫酶（ LDH）、活性氧（ ROS）和丙二醛（ MDA）水平。豨薟精醇和奇壬醇上調(diào)了磷酸化Janus激酶2/Janus激酶2（ p-JAK2/JAK2）和磷酸化信號轉導及轉錄激活蛋白3/信號轉導及轉錄激活蛋白3（p-STAT3/STAT3）的值，降低了Bcl-2相關X蛋白/B淋巴細胞瘤-2（Bax/Bcl-2）值，下調(diào)了半胱天冬酶-9（Caspase-9）和半胱天冬酶-3（ Caspase-3 ）的表達。結論 篩選獲得豨薟草活性成分豨薟精醇和奇壬醇，可通過激活JAK2/STAT3信號通路抑制氧化應激和減少細胞凋亡，發(fā)揮抗心肌缺氧損傷作用。

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

北京中醫(yī)藥大學東直門醫(yī)院2023年度科技創(chuàng)新專項（DZMKJCX-2023-025）；北京中醫(yī)藥大學2022年度基本科研業(yè)務費（2022-JYB-SYS-005）；北京中醫(yī)藥大學重點實驗室項目（1000061222482）