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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (1): 32-41.doi: 10.12092/j.issn.1009-2501.2025.01.004

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Exploring the mechanism of Xin Mai Jia in inhibiting hypertensive cardiac hypertrophy based on network pharmacology and animal experiments

LEI Chengjing1,2,3, YU Miao1,2,3, LI Yange1,2,3, TANG Xiaoguang1,2,3, ZHAO Fanrong1,2,3, ZHU Tiantian1,2,3   

  1. 1 School of Pharmacy, Xinxiang Medical College, Xinxiang 453500, Henan, China; 2 Henan International Joint Laboratory of Cardiovascular Reconstruction and Drug Intervention, Xinxiang 453500, Henan, China; 3 Xinxiang Key Laboratory of Cardiovascular Reconstruction Intervention and Molecular Targeted therapy, Xinxiang 453500, Henan, China
  • Received:2023-11-16 Revised:2024-08-16 Online:2025-01-26 Published:2025-01-02

Abstract:

AIM: To exploring the mechanism of Xin Mai Jia (XMJ) in inhibiting hypertensive cardiac hypertrophy through network pharmacology and animal experiments. METHODS: Retrieving the active ingredients and target points of XMJ by searching the TCMSP database and related literature reports; using the Gene Cards, OMIM, and Drug Bank databases to screen targets for hypertensive cardiac hypertrophy; constructing a network of traditional Chinese medicine-active ingredients-potential targets and a protein-protein interaction (PPI) network; using DAVID software for target gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; using Auto Dock software for molecular docking. A spontaneously hypertensive rat (SHR) model was established, and hematoxylin-eosin (HE) staining was used to detect the morphology of cardiac tissue and cellular hypertrophy, Masson staining was used to detect collagen deposition in cardiac tissue, and Western blot to detect the expression of heat shock protein (HSP90AA1), mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptor γ (PPARG), and tumor necrosis factor (TNF-α) in cardiac tissue. RESULTS: A total of 56 potential active ingredients were identified in XMJ, and 5,492 targets related to hypertensive cardiac hypertrophy were obtained. The targets in the core network were ranked according to their Degree values, and four main targets were selected: HSP90AA1, mTOR, PPARG, and TNF-α. The results of HE staining showed that compared with the normal group, the average area of cardiomyocytes in the SHR group increased significantly (P<0.05), while there was no significant change in the XMJ group. The hypertrophy in the SHR+XMJ group was significantly alleviated (P<0.05). The results of Masson staining showed that compared with the normal group, the levels of interstitial fibrosis and perivascular fibrosis in the SHR group rats increased significantly (P<0.01), and XMJ could significantly reduce the fibrosis levels in the SHR group rats (P<0.01). The results of Western blot showed that compared with the normal group rats, the expression of HSP90AA1 and PPARG in the myocardial tissue of SHR group rats was downregulated, mTOR phosphorylation was downregulated, and TNF-α was significantly upregulated (P<0.01). In the SHR+XMJ group, the expression of HSP90AA1, PPARG, and TNF-α in the myocardial tissue of rats returned to normal levels, and mTOR phosphorylation returned to normal levels. In the XMJ group, there were no significant changes in the above indicators compared with the normal group rats. CONCLUSION: The mechanism underlying the inhibitory effect of XMJ on myocardial cell hypertrophy in hypertension involves a comprehensive action through multiple components, multiple targets, and multiple pathways.

Key words: network pharmacology, molecular docking, Xin Mai Jia, myocardial hypertrophy, core targets, molecular docking

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