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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1442831

Puerarin attenuates myocardial ischemic injury and endoplasmic reticulum stress through upregulating Mzb1 signal pathway

Provisionally accepted
Jiaojiao Xue Jiaojiao Xue 1Ren Haolin Ren Haolin 2Qi Zhang Qi Zhang 1Jing Gu Jing Gu 1Qian Xu Qian Xu 1Jiaxi Sun Jiaxi Sun 1Lu Zhang Lu Zhang 1*Ming-Sheng Zhou Ming-Sheng Zhou 1*
  • 1 Shenyang Medical College, Shenyang, China
  • 2 First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning Province, China

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

    Objective: This study investigated the role of Mzb1 in puerarin protection against heart injury and dysfunction in acute myocardial infarction (AMI) mice.Methods: C57BL/6 mice were pretreated with and without puerarin at doses of 50 mg/kg and 100 mg/kg for 14 days before the establishment of AMI model. An AMI model was induced by the ligation of the left descending anterior coronary artery, and AC16 cardiomyocytes were treated with H2O2 in vitro. Echocardiography was performed to measure cardiac function. DHE staining, NADPH oxidase assay and DCFH-DA oxidative fluorescence staining were used to determine ROS production in vivo and in vitro respectively. Bioinformatics analysis was used to predict potential upstream transcription factors of Mzb1.Results: Puerarin dose-dependently reduced myocardial infarction area and injury accompanied by the improvement of cardiac function in AMI mice. AMI mice manifested an increase in myocardial oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and mitochondrial biogenesis dysfunction, which were inhibited by pretreatment with puerarin. Puerarin also prevented Mzb1 downregulation in the heart of AMI mice or H2O2-treated AC16 cells. Consistent with the in vivo findings, puerarin inhibited H2O2-induced cardiomyocyte apoptosis, ER stress and mitochondrial dysfunction, which were attenuated by siRNA Mzb1. Furthermore, JASPAR website predicted that KLF4 may be a transcription factor for Mzb1. The expression of KLF4 was partially reversed by puerarin in the cardiomyocytes injury model, and KLF4 inhibitor (Kenpaullone) inhibited Mzb1 expression and affect its function.Conclusions: These results suggest that puerarin can protect against cardiac injury by attenuating oxidative stress and endoplasmic reticulum stress through upregulating KLF4/Mzb1 pathway, and that puerarin may expand our armamentarium for the prevention and treatment of ischemic heart diseases.

    Keywords: Puerain1, acute myocardial infarction2, endoplasmic reticulum3, Mitochondria function4, Mzb15

    Received: 03 Jun 2024; Accepted: 23 Jul 2024.

    Copyright: © 2024 Xue, Haolin, Zhang, Gu, Xu, Sun, Zhang and Zhou. 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:
    Lu Zhang, Shenyang Medical College, Shenyang, China
    Ming-Sheng Zhou, Shenyang Medical College, Shenyang, 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.