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Uncovering the Mechanism of Chinese Hawthorn Leaf on Myocardial Ischemia Based on Network Pharmacology, Molecular Docking Verification, and In Vitro Studies

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A Correction to this article was published on 25 April 2024

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Abstract

Hawthorn leaf has shown therapeutic effects in the patients with myocardial ischemia. Our study combines network pharmacology, molecular docking techniques, and in vitro experiment with the aim of revealing the mechanism of hawthorn leaves in the treatment of myocardial ischemia. The active ingredients and corresponding targets of hawthorn leaf through Traditional Chinese Medicine System Pharmacology and Swiss Target Prediction databases. Targets related to myocardial ischemia were retrieved by Gene Card, Online Mendelian Inheritance in Man, Disgenet, and Therapeutic Targets Database databases. Cytoscape software was used to construct an ingredient–target–organ network and enrichment analysis of common targets was analyzed. Molecular docking verification of the core compound and target interactions was performed using MOE software. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. Six active components and 107 potential therapeutic targets were screened. The protein–protein interaction network analysis indicated that 10 targets, including AKT1 and EGFR, were hub genes. Quercetin, kaempferol and isorhamnetin were taken as core active components. Through pathway enrichment analysis, nearly 455 Gene Ontology entries and 77 Kyoto Encyclopedia of Genes and Genomes pathways were obtained, mainly including PI3K/Akt, estrogen and other signaling pathways. Molecular docking prediction showed that three main active ingredients were firmly combined with the core targets. Cellular experiments showed that quercetin alleviated oxidative damage in cells and regulated the expression of PI3K, P-AKT/AKT and Bax/Bcl-2 proteins. This study identified the potential targets of Hawthorn leaf against myocardial ischemia using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Hawthorn leaf in treatment of myocardial ischemia.

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Acknowledgements

We would like to thank the Provincial Science and Technology Plan of Hebei Province (Grant numbers 20372507D), Hebei Provincial Science and Technology Department's "Technological Innovation Guidance Project-Scientific and Technological Work Consultation" (Grant number 2020), and Key discipline Construction Project of Colleges and Universities in Hebei Province (Grant number Ji Jiao Gao [2013] 4).

Funding

The Provincial Science and Technology Plan of Hebei Province (Grant Number 20372507D), Key discipline Construction Project of Colleges and Universities in Hebei Province (Grant Number Ji Jiao Gao (2013) 4).

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Authors and Affiliations

  1. Hebei Key Laboratory of Study and Exploitation of Chinese Medicine, Chengde Medical College, Anyuan Road, Shuangqiao District, Chengde, 067000, Hebei, China

    Jingyun Gao, Yueyue Wang, Hui Xiong, Shengnan Zhao, Mingmei He, Meiting He & Haifeng Pan

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  1. Jingyun Gao
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Contributions

(I) Conception and design: JG, YW, XH; (II) Administrative support: HP; (III) Collection and assembly of data: SZ; (IV) Data analysis and interpretation: JG; (V) Manuscript writing: JG, YW, XH; (VI) Final approval of manuscript: All authors.

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Correspondence to Haifeng Pan.

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Gao, J., Wang, Y., Xiong, H. et al. Uncovering the Mechanism of Chinese Hawthorn Leaf on Myocardial Ischemia Based on Network Pharmacology, Molecular Docking Verification, and In Vitro Studies. Cardiovasc Toxicol 24, 171–183 (2024). https://doi.org/10.1007/s12012-024-09825-w

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