基于网络药理学、多组学和分子生物学相结合的策略阐明益气通络颗粒对脑缺血/再灌注损伤的作用机制。
Elucidation of the mechanism of Yiqi Tongluo Granule against cerebral ischemia/reperfusion injury based on a combined strategy of network pharmacology, multi-omics and molecular biology.
机构信息
Institute for Chinese Materia Medica, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory of TCM Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100730, China.
Department of Neurology, Medical College, Institute of Translational Medicine, Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225001, China.
出版信息
Phytomedicine. 2023 Sep;118:154934. doi: 10.1016/j.phymed.2023.154934. Epub 2023 Jun 25.
BACKGROUND
Ischemic stroke is caused by local lesions of the central nervous system and is a severe cerebrovascular disease. A traditional Chinese medicine, Yiqi Tongluo Granule (YQTL), shows valuable therapeutic effects. However, the substances and mechanisms remain unclear.
PURPOSE
We combined network pharmacology, multi-omics, and molecular biology to elucidate the mechanisms by which YQTL protects against CIRI.
STUDY DESIGN
We innovatively created a combined strategy of network pharmacology, transcriptomics, proteomics and molecular biology to study the active ingredients and mechanisms of YQTL. We performed a network pharmacology study of active ingredients absorbed by the brain to explore the targets, biological processes and pathways of YQTL against CIRI. We also conducted further mechanistic analyses at the gene and protein levels using transcriptomics, proteomics, and molecular biology techniques.
RESULTS
YQTL significantly decreased the infarction volume percentage and improved the neurological function of mice with CIRI, inhibited hippocampal neuronal death, and suppressed apoptosis. Fifteen active ingredients of YQTL were detected in the brains of rats. Network pharmacology combined with multi-omics revealed that the 15 ingredients regulated 19 pathways via 82 targets. Further analysis suggested that YQTL protected against CIRI via the PI3K-Akt signaling pathway, MAPK signaling pathway, and cAMP signaling pathway.
CONCLUSION
We confirmed that YQTL protected against CIRI by inhibiting nerve cell apoptosis enhanced by the PI3K-Akt signaling pathway.
背景
缺血性脑卒中是由中枢神经系统的局部病变引起的，是一种严重的脑血管疾病。一种中药，益气通络颗粒（YQTL），表现出有价值的治疗效果。然而，物质和机制仍不清楚。
目的
我们结合网络药理学、多组学和分子生物学来阐明 YQTL 防治 CIRI 的机制。
研究设计
我们创新性地创建了网络药理学、转录组学、蛋白质组学和分子生物学相结合的策略，研究 YQTL 的活性成分和作用机制。我们进行了网络药理学研究，以探索 YQTL 对 CIRI 的作用靶点、生物过程和途径。我们还使用转录组学、蛋白质组学和分子生物学技术在基因和蛋白质水平上进行了进一步的机制分析。
结果
YQTL 显著降低 CIRI 小鼠的梗死体积百分比，改善其神经功能，抑制海马神经元死亡，抑制细胞凋亡。在大鼠脑中检测到 YQTL 的 15 种活性成分。网络药理学结合多组学研究表明，这 15 种成分通过 82 个靶点调节 19 条通路。进一步分析表明，YQTL 通过 PI3K-Akt 信号通路、MAPK 信号通路和 cAMP 信号通路保护 CIRI。
结论
我们证实 YQTL 通过抑制 PI3K-Akt 信号通路增强的神经细胞凋亡来防治 CIRI。
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