Guo Siyu, Tan Yingying, Huang Zhihong, Li Yikui, Liu Weiyu, Fan Xiaotian, Zhang Jingyuan, Stalin Antony, Fu Changgeng, Wu Zhishan, Wang Penglong, Zhou Wei, Liu Xinkui, Wu Chao, Jia Shanshan, Zhang Jinyan, Duan Xiaoxia, Wu Jiarui
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Feb 23;13:839936. doi: 10.3389/fphar.2022.839936. eCollection 2022.
Danhong injection (DHI) is a traditional Chinese medicine preparation commonly used in the clinical treatment of acute myocardial infarction (AMI). In this study, the active components of DHI and its mechanism in the treatment of AMI were investigated. The chemical components of DHI were detected by the ultra-high-performance liquid chromatography-linear trap quadrupole-orbitrap-tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS), and the targets and pathways of DHI in the treatment of AMI were analyzed by systems pharmacology, which was verified by molecular docking and animal experiments. A total of 12 active components of DHI were obtained, and 158 common targets of component and disease were identified by systems pharmacology. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that DHI is closely related to the calcium signaling pathway in the treatment of AMI. Molecular docking showed that the key target protein has good binding affinity to related compounds. The experimental results showed that compared with the model group, LVAWs, EF, and FS significantly ( < 0.05) increased in the DHI group. The percentage of myocardial infarction significantly ( < 0.01) decreased, both in the ventricular and total cardiac regions, and the pathological damage of myocardial tissue also decreased. In addition, the expression of the protein CaMK II decreased ( < 0.01) and the expression of SERCA significantly increased ( < 0.01). This study revealed that ferulic acid, caffeic acid and rosmarinic acid could inhibit AMI by regulating PLB, CaMK II, SERCA, etc. And mechanistically, calcium signaling pathway was critically involved. Combination of systems pharmacology prediction with experimental validation may provide a scientific basis for in-depth clinical investigation of the material basis of DHI.
丹红注射液（DHI）是临床治疗急性心肌梗死（AMI）常用的一种中药制剂。本研究对DHI的活性成分及其治疗AMI的机制进行了探究。采用超高效液相色谱-线性离子阱四极杆-轨道阱串联质谱（UHPLC-LTQ-Orbitrap-MS/MS）检测DHI的化学成分，并通过系统药理学分析DHI治疗AMI的靶点和通路，再经分子对接和动物实验进行验证。共获得DHI的12种活性成分，通过系统药理学鉴定出158个成分与疾病的共同靶点。京都基因与基因组百科全书（KEGG）分析结果显示，DHI在治疗AMI方面与钙信号通路密切相关。分子对接表明关键靶蛋白与相关化合物具有良好的结合亲和力。实验结果显示，与模型组相比，DHI组的左室后壁厚度（LVAWs）、射血分数（EF）和短轴缩短率（FS）显著升高（<0.05）。心室和全心梗死面积百分比均显著降低（<0.01），心肌组织的病理损伤也减轻。此外，蛋白钙/钙调蛋白依赖性蛋白激酶II（CaMK II）的表达降低（<0.01），而肌浆网钙ATP酶（SERCA）的表达显著升高（<0.01）。本研究表明，阿魏酸、咖啡酸和迷迭香酸可通过调节受磷蛋白（PLB）､CaMK II、SERCA等抑制AMI。从机制上讲，钙信号通路起关键作用。系统药理学预测与实验验证相结合可为深入临床研究DHI的物质基础提供科学依据。
