PMID- 35935870 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220809 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification. PG - 927488 LID - 10.3389/fphar.2022.927488 [doi] LID - 927488 AB - Background: Myocardial infarction (MI), characterized by reduced blood flow to the heart, is a coronary artery disorder with the highest morbidity and mortality among cardiovascular diseases. Consequently, there is an urgent need to identify effective drugs to treat MI. Rhizoma Corydalis (RC) is the dry tuber of Corydalis yanhusuo W.T. Wang, and is extensively applied in treating MI clinically in China. Its underlying pharmacological mechanism remains unknown. This study aims to clarify the molecular mechanism of RC on MI by utilizing network pharmacology and experimental verification. Methods: Based on network pharmacology, the potential targets of the RC ingredients and MI-related targets were collected from the databases. Furthermore, core targets of RC on MI were identified by the protein-protein interaction (PPI) network and analyzed with Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to validate the binding affinity between the core targets and the bioactive components. Oxygen-glucose deprivation (OGD) was performed on H9c2 cells to mimic MI in vitro. A Cell Counting Kit-8 assay was used to assess the cardioprotective effect of the active ingredient against OGD. Western blot analysis and RT-qPCR were used to measure the cell apoptosis and inflammation level of H9c2 cells. Results: The network pharmacology obtained 60 bioactive components of RC, 431 potential targets, and 1131 MI-related targets. In total, 126 core targets were screened according to topological analysis. KEGG results showed that RC was closely related to the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB, also called Akt) signaling pathway. The experimental validation data showed that tetrahydropalmatine (THP) pretreatment preserved cell viability after OGD exposure. THP suppressed cardiomyocyte apoptosis and inflammation induced by OGD, while LY294002 blocked the inhibition effect of THP on OGD-induced H9c2 cell injury. Moreover, the molecular docking results indicated that THP had the strongest binding affinity with Akt over berberine, coptisine, palmatine, and quercetin. Conclusion: THP, the active ingredient of RC, can suppress OGD-induced H9c2 cell injury by activating the PI3K/Akt pathway, which in turn provides a scientific basis for a novel strategy for MI therapy and RC application. CI - Copyright (c) 2022 Li, Wu, Huang, Cheng, Wang and Liu. FAU - Li, Jingyan AU - Li J AD - Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research International, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Wu, Junxuan AU - Wu J AD - Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research International, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Shunde Hospital of Guangzhou University of Translational Chinese Medicine, Foshan, China. AD - The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Huang, Junying AU - Huang J AD - College of Life Sciences, Guangzhou University, Guangzhou, China. FAU - Cheng, Yuanyuan AU - Cheng Y AD - Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research International, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Wang, Dawei AU - Wang D AD - Shunde Hospital of Guangzhou University of Translational Chinese Medicine, Foshan, China. FAU - Liu, Zhongqiu AU - Liu Z AD - Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research International, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. LA - eng PT - Journal Article DEP - 20220722 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9355031 OTO - NOTNLM OT - Corydalis yanhusuo OT - PI3k/Akt signaling pathway OT - apoptosis OT - myocardial infarction OT - network pharmacology OT - tetrahydropalmatine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/09 06:00 MHDA- 2022/08/09 06:01 PMCR- 2022/07/22 CRDT- 2022/08/08 03:40 PHST- 2022/04/24 00:00 [received] PHST- 2022/06/21 00:00 [accepted] PHST- 2022/08/08 03:40 [entrez] PHST- 2022/08/09 06:00 [pubmed] PHST- 2022/08/09 06:01 [medline] PHST- 2022/07/22 00:00 [pmc-release] AID - 927488 [pii] AID - 10.3389/fphar.2022.927488 [doi] PST - epublish SO - Front Pharmacol. 2022 Jul 22;13:927488. doi: 10.3389/fphar.2022.927488. eCollection 2022.