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Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling
Cardiovascular disease, a disease caused by many pathogenic factors, is one of the most common causes of death worldwide, and oxidative stress plays a major role in its pathophysiology. Tanshinone I (Tan I), a natural compound with cardiovascular protective effects, is one of the main active compoun...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167655/ https://www.ncbi.nlm.nih.gov/pubmed/34084132 http://dx.doi.org/10.3389/fphar.2021.644116 |
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author | Wu, Yu-Ting Xie, Ling-Peng Hua, Yue Xu, Hong-Lin Chen, Guang-Hong Han, Xin Tan, Zhang-Bin Fan, Hui-Jie Chen, Hong-Mei Li, Jun Liu, Bin Zhou, Ying-Chun |
author_facet | Wu, Yu-Ting Xie, Ling-Peng Hua, Yue Xu, Hong-Lin Chen, Guang-Hong Han, Xin Tan, Zhang-Bin Fan, Hui-Jie Chen, Hong-Mei Li, Jun Liu, Bin Zhou, Ying-Chun |
author_sort | Wu, Yu-Ting |
collection | PubMed |
description | Cardiovascular disease, a disease caused by many pathogenic factors, is one of the most common causes of death worldwide, and oxidative stress plays a major role in its pathophysiology. Tanshinone I (Tan I), a natural compound with cardiovascular protective effects, is one of the main active compounds extracted from Salvia miltiorrhiza. Here, we investigated whether Tan I could attenuate oxidative stress and oxidative stress–induced cardiomyocyte apoptosis through Nrf2/MAPK signaling in vivo and in vitro. We found that Tan I treatment protected cardiomyocytes against oxidative stress and oxidative stress–induced apoptosis, based on the detection of relevant oxidation indexes such as reactive oxygen species, superoxide dismutase, malondialdehyde, and apoptosis, including cell viability and apoptosis-related protein expression. We further examined the mechanisms underlying these effects, determining that Tan I activated nuclear factor erythroid 2 (NFE2)–related factor 2 (Nrf2) transcription into the nucleus and dose-dependently promoted the expression of Nrf2, while inhibiting MAPK signaling activation, including P38 MAPK, SAPK/JNK, and ERK1/2. Nrf2 inhibitors in H9C2 cells and Nrf2 knockout mice demonstrated aggravated oxidative stress and oxidative stress–induced cardiomyocyte injury; Tan I treatment suppressed these effects in H9C2 cells; however, its protective effect was inhibited in Nrf2 knockout mice. Additionally, the analysis of surface plasmon resonance demonstrated that Tan I could directly target Nrf2 and act as a potential Nrf2 agonist. Collectively, these data strongly indicated that Tan I might inhibit oxidative stress and oxidative stress–induced cardiomyocyte injury through modulation of Nrf2 signaling, thus supporting the potential therapeutic application of Tan I for oxidative stress–induced CVDs. |
format | Online Article Text |
id | pubmed-8167655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81676552021-06-02 Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling Wu, Yu-Ting Xie, Ling-Peng Hua, Yue Xu, Hong-Lin Chen, Guang-Hong Han, Xin Tan, Zhang-Bin Fan, Hui-Jie Chen, Hong-Mei Li, Jun Liu, Bin Zhou, Ying-Chun Front Pharmacol Pharmacology Cardiovascular disease, a disease caused by many pathogenic factors, is one of the most common causes of death worldwide, and oxidative stress plays a major role in its pathophysiology. Tanshinone I (Tan I), a natural compound with cardiovascular protective effects, is one of the main active compounds extracted from Salvia miltiorrhiza. Here, we investigated whether Tan I could attenuate oxidative stress and oxidative stress–induced cardiomyocyte apoptosis through Nrf2/MAPK signaling in vivo and in vitro. We found that Tan I treatment protected cardiomyocytes against oxidative stress and oxidative stress–induced apoptosis, based on the detection of relevant oxidation indexes such as reactive oxygen species, superoxide dismutase, malondialdehyde, and apoptosis, including cell viability and apoptosis-related protein expression. We further examined the mechanisms underlying these effects, determining that Tan I activated nuclear factor erythroid 2 (NFE2)–related factor 2 (Nrf2) transcription into the nucleus and dose-dependently promoted the expression of Nrf2, while inhibiting MAPK signaling activation, including P38 MAPK, SAPK/JNK, and ERK1/2. Nrf2 inhibitors in H9C2 cells and Nrf2 knockout mice demonstrated aggravated oxidative stress and oxidative stress–induced cardiomyocyte injury; Tan I treatment suppressed these effects in H9C2 cells; however, its protective effect was inhibited in Nrf2 knockout mice. Additionally, the analysis of surface plasmon resonance demonstrated that Tan I could directly target Nrf2 and act as a potential Nrf2 agonist. Collectively, these data strongly indicated that Tan I might inhibit oxidative stress and oxidative stress–induced cardiomyocyte injury through modulation of Nrf2 signaling, thus supporting the potential therapeutic application of Tan I for oxidative stress–induced CVDs. Frontiers Media S.A. 2021-05-18 /pmc/articles/PMC8167655/ /pubmed/34084132 http://dx.doi.org/10.3389/fphar.2021.644116 Text en Copyright © 2021 Wu, Xie, Hua, Xu, Chen, Han, Tan, Fan, Chen, Li, Liu and Zhou. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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. |
spellingShingle | Pharmacology Wu, Yu-Ting Xie, Ling-Peng Hua, Yue Xu, Hong-Lin Chen, Guang-Hong Han, Xin Tan, Zhang-Bin Fan, Hui-Jie Chen, Hong-Mei Li, Jun Liu, Bin Zhou, Ying-Chun Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling |
title | Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling |
title_full | Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling |
title_fullStr | Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling |
title_full_unstemmed | Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling |
title_short | Tanshinone I Inhibits Oxidative Stress–Induced Cardiomyocyte Injury by Modulating Nrf2 Signaling |
title_sort | tanshinone i inhibits oxidative stress–induced cardiomyocyte injury by modulating nrf2 signaling |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167655/ https://www.ncbi.nlm.nih.gov/pubmed/34084132 http://dx.doi.org/10.3389/fphar.2021.644116 |
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