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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1510380
This article is part of the Research Topic Natural Products and Immune Inflammation: Mechanistic Understanding Based on Systems Biology View all 19 articles

Mechanistic Analysis of Tanshinone IIA's Regulation of the ATM/GADD45/ORC Signaling Pathway to Reduce Myocardial Ischemia-Reperfusion Injury

Provisionally accepted
Yiwei Sang Yiwei Sang 1Jiangnan Du Jiangnan Du 1Dilimulati Zulikala Dilimulati Zulikala 1Zhongqiang Sang Zhongqiang Sang 2*
  • 1 Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
  • 2 Department of Dermatology Shanghai Zhongye Hospital, Shanghai, China

The final, formatted version of the article will be published soon.

    Background: By far, one of the best treatments for myocardial ischemia is reperfusion therapy. The primary liposoluble component of Danshen, a traditional Chinese herbal remedy, Tanshinone Ⅱ A, has been shown to have cardiac healing properties. The purpose of this work is to investigate the processes by which Tanshinone Ⅱ A influences myocardial ischemia-reperfusion injury (MIRI) in the H9C2 cardiac myoblast cell line, as well as the association between Tanshinone ⅡA and MIRI.The cardiac cells were divided into a normal group, a model group and Tanshinone ⅡA treatment groups. After 4 h of culture with the deprivation of oxygen and glucose, the cells were incubated normally for 2 h. The success of the model and the capacity of Tanshinone Ⅱ A to heal cardiac damage were validated by the outcomes of cell viability, morphology, and proliferation. The efficacy of Tanshinone ⅡA in treating MIRI was further confirmed by the scratch assay and biomarker measurement. The differentially expressed genes were examined using transcriptome sequencing. The Ataxia-Telangiectasia Mutated (ATM)/Growth Arrest and DNA Damage (GADD45)/Origin Recognition Complex (ORC) signaling pathway was identified as being crucial to this process by KEGG pathway analysis and GO enrichment. Molecular docking and RT-qPCR were used to confirm our results. The crucial function of the ATM/GADD45/ORC pathway was further confirmed by the addition of an ATM inhibitor, which inhibited the expression of ATM.Tanshinone ⅡA can relieve the myocardial ischemia-reperfusion injury in cardiac cells by activating the ATM/GADD45/ORC pathway.

    Keywords: Myocardial ischemia-reperfusion injury, H9c2, ATM, GADD45, ORC Myocardial ischemia-reperfusion injury, ORC

    Received: 12 Oct 2024; Accepted: 12 Dec 2024.

    Copyright: © 2024 Sang, Du, Zulikala and Sang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhongqiang Sang, Department of Dermatology Shanghai Zhongye Hospital, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.