School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
Department of Pharmacy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China.
Chin J Integr Med. 2023 Dec;29(12):1087-1098. doi: 10.1007/s11655-023-3644-x. Epub 2023 Aug 22.
To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI).
First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro.
MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model.
THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.
探讨延胡索乙素（THP）对急性心肌缺血（AMI）的潜在分子机制。
首先，分别从 SymMap 数据库、中药数据库及分析平台、SwissTargetPrediction 收集 THP 和 AMI 的靶基因，然后评估 THP 和 AMI 的重叠靶基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析及蛋白质-蛋白质相互作用网络分析。采用分子对接评估蛋白与 THP 的结合亲和力。最后，在体内和体外分别探讨 THP 对 AMI 模型和 H9C2 心肌细胞氧葡萄糖剥夺（OGD）模型的保护作用，并通过 RT-qPCR 检测靶基因的表达水平。
MMP9、PPARG、PTGS2、SLC6A4、ESR1、JAK2、GSK3B、NOS2 和 AR 被认为是关键基因。KEGG 富集分析结果表明，THP 的潜在靶基因参与了 PPAR 和激素途径的调节。THP 改善了心脏功能，减轻了心肌细胞损伤。此外，THP 显著降低了 AMI 后 MMP9、PTGS2、SLC6A4、GSK3B 和 ESR1 的 RNA 表达水平（P<0.05，P<0.01）。在体外，THP 显著增加了 H9C2 心肌细胞活力（P<0.05，P<0.01），并抑制了 OGD 模型中 PPARG、ESR1 和 AR 的 RNA 表达水平（P<0.05，P<0.01）。
THP 可改善 AMI 患者的心脏功能，减轻心肌损伤。其作用机制可能与抑制炎症、改善能量代谢和调节激素有关。
