NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress

Abstract Doxorubicin (DOX) is an anthracycline antibiotic used in the clinical treatment of cancer, but its use is limited due to its cardiotoxic effects. Therefore, it is necessary to explore natural compounds that are effective in protecting against the cardiotoxicity caused by DOX. Neutral Morche...

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Autores principales: Na Xu, Yi Lu, Xinmiao Yao, Rui Zhao, Zhebin Li, Jialei Li, Yinglei Zhang, Bo Li, Ye Zhou, Huifang Shen, Liqun Wang, Kaixin Chen, Li Yang, Shuwen Lu
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Publicado: Wiley 2021
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spelling oai:doaj.org-article:008dfff0966e4904aef051697cb27e2c2021-11-04T13:06:43ZNMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress2048-717710.1002/fsn3.2586https://doaj.org/article/008dfff0966e4904aef051697cb27e2c2021-11-01T00:00:00Zhttps://doi.org/10.1002/fsn3.2586https://doaj.org/toc/2048-7177Abstract Doxorubicin (DOX) is an anthracycline antibiotic used in the clinical treatment of cancer, but its use is limited due to its cardiotoxic effects. Therefore, it is necessary to explore natural compounds that are effective in protecting against the cardiotoxicity caused by DOX. Neutral Morchella conica polysaccharides‐2 (NMCP‐2) is a natural polysaccharide with antioxidant activity that was isolated and purified from Morchella conica in our laboratory's previous study. This study aimed to investigate the possible protective effect of NMCP‐2 on DOX‐induced cardiotoxicity and the potential underlying mechanisms. The model of DOX‐induced H9C2 cells and the model of DOX‐induced mice were used in this study. In in vitro studies of H9C2 myocardial cells, NMCP‐2 effectively increased the activity of H9C2 cells, reducing the levels of lactate dehydrogenase (LDH). In the mouse model of DOX‐induced chronic cardiotoxicity, NMCP‐2 significantly reduced the cardiac index, reduced the release of serum cardiac enzymes, and improved the pathology of murine myocardial tissues, thereby alleviating DOX‐induced cardiotoxicity. Further mechanism studies showed that pretreatment with NMCP‐2 counteracted the oxidative stress induced by DOX, as indicated by increasing superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) activities, and malondialdehyde (MDA) production decreased. In addition, we observed NMCP‐2 inhibited the activation of the mitochondrial apoptosis pathway and regulated the disordered expression of Bcl‐2 and Bax in the myocardial tissues of DOX‐treated mice. These findings indicated that NMCP‐2, a natural bioactive compound, could potentially be used as a food supplement to reduce the cardiotoxicity caused by DOX.Na XuYi LuXinmiao YaoRui ZhaoZhebin LiJialei LiYinglei ZhangBo LiYe ZhouHuifang ShenLiqun WangKaixin ChenLi YangShuwen LuWileyarticlecardiotoxicitydoxorubicinmitochondrial apoptosisNMCP‐2oxidative stressNutrition. Foods and food supplyTX341-641ENFood Science & Nutrition, Vol 9, Iss 11, Pp 6262-6273 (2021)
institution DOAJ
collection DOAJ
language EN
topic cardiotoxicity
doxorubicin
mitochondrial apoptosis
NMCP‐2
oxidative stress
Nutrition. Foods and food supply
TX341-641
spellingShingle cardiotoxicity
doxorubicin
mitochondrial apoptosis
NMCP‐2
oxidative stress
Nutrition. Foods and food supply
TX341-641
Na Xu
Yi Lu
Xinmiao Yao
Rui Zhao
Zhebin Li
Jialei Li
Yinglei Zhang
Bo Li
Ye Zhou
Huifang Shen
Liqun Wang
Kaixin Chen
Li Yang
Shuwen Lu
NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
description Abstract Doxorubicin (DOX) is an anthracycline antibiotic used in the clinical treatment of cancer, but its use is limited due to its cardiotoxic effects. Therefore, it is necessary to explore natural compounds that are effective in protecting against the cardiotoxicity caused by DOX. Neutral Morchella conica polysaccharides‐2 (NMCP‐2) is a natural polysaccharide with antioxidant activity that was isolated and purified from Morchella conica in our laboratory's previous study. This study aimed to investigate the possible protective effect of NMCP‐2 on DOX‐induced cardiotoxicity and the potential underlying mechanisms. The model of DOX‐induced H9C2 cells and the model of DOX‐induced mice were used in this study. In in vitro studies of H9C2 myocardial cells, NMCP‐2 effectively increased the activity of H9C2 cells, reducing the levels of lactate dehydrogenase (LDH). In the mouse model of DOX‐induced chronic cardiotoxicity, NMCP‐2 significantly reduced the cardiac index, reduced the release of serum cardiac enzymes, and improved the pathology of murine myocardial tissues, thereby alleviating DOX‐induced cardiotoxicity. Further mechanism studies showed that pretreatment with NMCP‐2 counteracted the oxidative stress induced by DOX, as indicated by increasing superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) activities, and malondialdehyde (MDA) production decreased. In addition, we observed NMCP‐2 inhibited the activation of the mitochondrial apoptosis pathway and regulated the disordered expression of Bcl‐2 and Bax in the myocardial tissues of DOX‐treated mice. These findings indicated that NMCP‐2, a natural bioactive compound, could potentially be used as a food supplement to reduce the cardiotoxicity caused by DOX.
format article
author Na Xu
Yi Lu
Xinmiao Yao
Rui Zhao
Zhebin Li
Jialei Li
Yinglei Zhang
Bo Li
Ye Zhou
Huifang Shen
Liqun Wang
Kaixin Chen
Li Yang
Shuwen Lu
author_facet Na Xu
Yi Lu
Xinmiao Yao
Rui Zhao
Zhebin Li
Jialei Li
Yinglei Zhang
Bo Li
Ye Zhou
Huifang Shen
Liqun Wang
Kaixin Chen
Li Yang
Shuwen Lu
author_sort Na Xu
title NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
title_short NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
title_full NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
title_fullStr NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
title_full_unstemmed NMCP‐2 polysaccharide purified from Morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
title_sort nmcp‐2 polysaccharide purified from morchella conica effectively prevents doxorubicin‐induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress
publisher Wiley
publishDate 2021
url https://doaj.org/article/008dfff0966e4904aef051697cb27e2c
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