PHB1 Attenuates Triptolide-induced Cardiotoxicity by Regulating Mitochondrial Dynamics in Cultured Newborn Mice Cardiomyocytes - Abstract

Sep 29, 2026

Uploaded by Fans

Triptolide (TP), used clinically for multiple diseases, is limited by cardiotoxicity whose mechanisms remain unclear. Mitochondrial dysfunction and apoptosis of cardiomyocytes emerge as key processes in TP-induced cardiotoxicity. TP decreases prohibitin1 (PHB1) expression in a time-dependent manner, while PHB1 overexpression alleviates mitochondrial dysfunction and suppresses cardiomyocyte apoptosis. PHB1 may regulate mitochondrial dynamics to maintain normal mitochondrial function, suggesting PHB1 as a potential therapeutic target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Introduction

Materials and Methods

PHB1 Attenuates Triptolide-induced Cardiotoxicity by Regulating Mitochondrial Dynamics in Cultured Newborn Mice Cardiomyocytes Wanlin Chen, MM* and XinGuo Li, MM† Abstract: Triptolide (TP) is widely used clinically for multiple diseases, but its cardiotoxicity signiﬁcantly limits its clinical applications. The underlying mechanisms of its cardiotoxicity are still unclear. Mitochondria are crucial for cellular survival and function. Here, we found that TP induced mitochondrial dysfunction and apoptosis of cardiomyocytes, which might be the key process underlying TP-induced cardiotoxicity. Moreover, the expression of prohibitin1 (PHB1) was signiﬁcantly decreased after TP treatment ina time-dependent manner. Overexpression of PHB1 alleviated mitochondrial dysfunction and inhibited apoptosis of cardiomyocytes after TP treatment. Mechanistically, PHB1 might regulate mitochondrial dynamics, which maintain normal mitochondrial function. Based on the above results, PHB1 might be a potential therapeutic target for TP-induced cardiotoxicity. Key Words: triptolide, cardiotoxicity, mitochondrial dynamics, apoptosis, PHB1 (J Cardiovasc Pharmacol 􀀁 2026;87:51–60) INTRODUCTION Triptolide (TP), a bioactive constituent isolated from the traditional Chinese herb Tripterygium wilfordii (Thunder God Vine), is widely used for the treatment of rheumatic disease, cancers, and nephrotic syndrome. But its clinical applications are highly limited by multiorgan damage, Received for publication September 28, 2024; accepted September 27, 2025. From the *Department of Cardiology, Baoji People’s Hospital, the Fifth Clinical Medical School of Medical College of Yan’an University, Baoji, China; and †Department of Cardiology, Xianyang Hospital of Yan’an University, Xianyang, China. The authors report no conﬂicts of interest. X. Li and W. Chen contributed to the study conception, and W. Chen designed the study. W. Chen performed the experiments and wrote the ﬁrst draft. W. Chen and X. Li revised the manuscript and approved the ﬁnal version. All authors contributed to manuscript revisions and approved the submitted version. All experiments were performed in accordance with the National Institutes of Health (USA) guidelines. The protocol of the present study was approved by the ethical committee of Xianyang Hospital of Yan’an University. Data will be made available on request. Correspondence: Xinguo Li, MM, Department of Cardiology, Xianyang Hospital of Yan’an University, No. 38 Wenlin Road, Xianyang, Shaanxi, 712000, China ([e-mail: Lixinguo198@163.com](e-mail: Lixinguo198@163.com)). Copyright © 2025 The Author(s) . Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. including cardiotoxicity.1 TP-induced cardiotoxicity presents as cardiomyocyte death, progressive heart enlargement, and heart failure,2 which ultimately induces unscheduled treatment discontinuation.3 Therefore, it is an urgent priority to clarify the underlying mechanism and identify therapeutic targets. Previous studies reported that triptolide inhibited the phosphorylations of AKT/mTOR pathway to induce abnormal cell death of cardiomyocytes.3 Mitochondria play significant role in cardiac normal function and cell death.4,5 Mitochondrial injury of cardiomyocytes is a notable feature in TP-induced cardiotoxicity, including unbalanced mitochondrial fusion and ﬁssion, decreased mitochondrial biogenesis, and dysregulation of mitophagy, which might ultimately induce cell apoptosis.6 These results indicate that mitochondrial injury plays a vital role in TP-induced cardiotoxicity. Strategies to protect mitochondrial structure and function could be potential

FAQs

What cardiotoxic effects of triptolide does the paper focus on?

It focuses on TP-induced cardiotoxicity presenting as cardiomyocyte death, progressive heart enlargement, and eventual heart failure.

How does PHB1 relate to triptolide-induced cardiotoxicity?

PHB1 expression decreases after TP treatment in a time-dependent manner, and restoring PHB1 by overexpression alleviates mitochondrial dysfunction and inhibits cardiomyocyte apoptosis.

What mechanism is proposed for PHB1’s protective effects?

PHB1 may regulate mitochondrial dynamics, thereby maintaining normal mitochondrial function and reducing TP-associated mitochondrial injury and apoptosis.

Sep 29, 2026

Uploaded by Fans