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Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and in vitro validation

  • Authors:
    • Haoying Li
    • Linlin Bu
    • Xiaoqi Sun
    • Xi Chu
    • Yucong Xue
    • Muqing Zhang
    • Jing Shi
    • Yanshuang Liu
    • Shengjiang Guan
    • Xue Han
    • Hongfang Wang
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China, Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050000, P.R. China, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 117
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    Published online on: January 29, 2024
       https://doi.org/10.3892/etm.2024.12405
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Abstract

Liquiritin (LIQ) is a flavonoid known for its cardioprotective properties, extracted from Glycyrrhiza uralensis Fisch. The purpose of the present study was to investigate the protective mechanism of LIQ against hypoxia/reoxygenation (H/R) injury through in vitro experiments, with the goal of enhancing its pharmacological effects. Initially, network pharmacology was employed to explore the targets and mechanisms of LIQ. Subsequently, an in vitro H/R model was established using H9c2 cells. Potential targets for LIQ and myocardial ischemia‑reperfusion injury (MIRI) were identified through online databases. The STRING, Cytoscape and DAVID databases were used to extract intersecting targets and mechanisms. In vitro experiments were conducted to validate these findings, assessing cardiac enzymes, oxidative stress indicators, mitochondrial fluorescence, apoptotic fluorescence, inflammation and related protein expression. The network pharmacological analysis revealed that the protective effects of LIQ on MIRI involve oxidative stress, inflammation and apoptosis. The results of in vitro experimental validation demonstrated that LIQ significantly reduced the activities of lactated dehydrogenase and creatine kinase isoenzyme‑MB (P<0.05 or 0.01), as well as the level of malondialdehyde (P<0.01). It also inhibited the production of reactive oxygen species (P<0.01), the release of inflammatory factors (P<0.05 or 0.01) and apoptosis (P<0.01). By contrast, the LIQ pre‑treatment group exhibited a significant increase in mitochondrial membrane potential level (P<0.05 or 0.01) and the activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (P<0.05 or 0.01). Furthermore, LIQ reduced the protein expressions of TNF‑α receptor type 1 (TNFR1) and MMP9, along with the level of NF‑κB phosphorylation (P<0.05 or 0.01). In conclusion, LIQ mitigated H/R‑induced cardiomyocyte injury through mechanisms that may involve antioxidants, anti‑apoptotic effects, protection against mitochondrial damage and suppression of inflammatory levels. These effects are achieved via inhibition of the TNFR1/NF‑κB/MMP9 pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Li H, Bu L, Sun X, Chu X, Xue Y, Zhang M, Shi J, Liu Y, Guan S, Han X, Han X, et al: Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation. Exp Ther Med 27: 117, 2024.
APA
Li, H., Bu, L., Sun, X., Chu, X., Xue, Y., Zhang, M. ... Wang, H. (2024). Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation. Experimental and Therapeutic Medicine, 27, 117. https://doi.org/10.3892/etm.2024.12405
MLA
Li, H., Bu, L., Sun, X., Chu, X., Xue, Y., Zhang, M., Shi, J., Liu, Y., Guan, S., Han, X., Wang, H."Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation". Experimental and Therapeutic Medicine 27.3 (2024): 117.
Chicago
Li, H., Bu, L., Sun, X., Chu, X., Xue, Y., Zhang, M., Shi, J., Liu, Y., Guan, S., Han, X., Wang, H."Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation". Experimental and Therapeutic Medicine 27, no. 3 (2024): 117. https://doi.org/10.3892/etm.2024.12405
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Bu L, Sun X, Chu X, Xue Y, Zhang M, Shi J, Liu Y, Guan S, Han X, Han X, et al: Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation. Exp Ther Med 27: 117, 2024.
APA
Li, H., Bu, L., Sun, X., Chu, X., Xue, Y., Zhang, M. ... Wang, H. (2024). Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation. Experimental and Therapeutic Medicine, 27, 117. https://doi.org/10.3892/etm.2024.12405
MLA
Li, H., Bu, L., Sun, X., Chu, X., Xue, Y., Zhang, M., Shi, J., Liu, Y., Guan, S., Han, X., Wang, H."Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation". Experimental and Therapeutic Medicine 27.3 (2024): 117.
Chicago
Li, H., Bu, L., Sun, X., Chu, X., Xue, Y., Zhang, M., Shi, J., Liu, Y., Guan, S., Han, X., Wang, H."Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and <em>in</em> <em>vitro</em> validation". Experimental and Therapeutic Medicine 27, no. 3 (2024): 117. https://doi.org/10.3892/etm.2024.12405
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