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Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia

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Abstract

Objective

To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI).

Methods

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.

Results

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.

Conclusions

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.

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Author information

Authors and Affiliations

  1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China

    Po-li Lin, Jun-ling Cao, Ping Ren, Bo-ya Cao, Chang-hui Zheng & Qi-wen Li

  2. Department of Pharmacy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China

    Jun-ling Cao

  3. School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China

    Jia-li Chen

  4. School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China

    Ping He &  Jian Zhang

  5. School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Wei Wang

  6. Beijing Key Laboratory of TCM Syndrome and Formula, Beijing, 100029, China

    Wei Wang &  Jian Zhang

  7. Key Laboratory of Beijing University of Chinese Medicine, Ministry of Education, Beijing, 100029, China

    Wei Wang &  Jian Zhang

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  1. Po-li Lin
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  2. Jun-ling Cao
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  9. Wei Wang
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  10. Jian Zhang
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Contributions

Zhang J conceived and designed the study. Lin PL, Ren P, Chen JL, He P, Cao BY and Li QW performed the experiments. Lin PL and Zheng CH performed the statistical analyses. Lin PL and Li QW drafted the manuscript. Zhang J, Wang W and Cao JL revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jian Zhang.

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The authors declare no conflict of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 82004095) and the Fundamental Research Funds for the Central Universities (No. 2021-JYB-XJSJJ031)

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Lin, Pl., Cao, Jl., Ren, P. et al. Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia. Chin. J. Integr. Med. 29, 1087–1098 (2023). https://doi.org/10.1007/s11655-023-3644-x

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