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Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation

Doxorubicin (DOX) is a potent chemotherapeutic agent that is used against various types of human malignancies. However, the associated risk of cardiotoxicity has limited its clinical application. Danhong injection (DHI) is a Chinese medicine with multiple pharmacological activities and is widely use...

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Autores principales: Yi, Xiaojiao, Wang, Fugen, Feng, Yan, Zhu, Junfeng, Wu, Yongjiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441549/
https://www.ncbi.nlm.nih.gov/pubmed/36071840
http://dx.doi.org/10.3389/fphar.2022.929302
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author Yi, Xiaojiao
Wang, Fugen
Feng, Yan
Zhu, Junfeng
Wu, Yongjiang
author_facet Yi, Xiaojiao
Wang, Fugen
Feng, Yan
Zhu, Junfeng
Wu, Yongjiang
author_sort Yi, Xiaojiao
collection PubMed
description Doxorubicin (DOX) is a potent chemotherapeutic agent that is used against various types of human malignancies. However, the associated risk of cardiotoxicity has limited its clinical application. Danhong injection (DHI) is a Chinese medicine with multiple pharmacological activities and is widely used for treating cardiovascular diseases. The aim of the present study was to evaluate the potential protective effect of DHI on DOX-induced cardiotoxicity in vivo and to investigate the possible underlying mechanisms. First, a sensitive and reliable HPLC−ESI-Q-TOF-MS/MS method was developed to comprehensively analyze the chemical compositions of DHI. A total of 56 compounds were identified, including phenolic acids, tanshinones, and flavonoids. Then, a DOX-induced chronic cardiotoxicity rat model was established to assess the therapeutic effect of DHI. As a result, DHI administration prevented the reduction in body weight and heart weight, and improved electrocardiogram performance. Additionally, the elevated levels of serum biochemical indicators were reduced, and the activities of oxidative enzymes were restored in the DOX-DHI group. Network pharmacology analysis further revealed that these effects might be attributed to 14 active compounds (e.g., danshensu, salvianolic acid A, salvianolic acid B, rosmarinic acid, and tanshinone IIA) and 15 potential targets (e.g., CASP3, SOD1, NOS3, TNF, and TOP2A). The apoptosis pathway was highly enriched according to the KEGG analysis. Molecular docking verified the good binding affinities between the active compounds and the corresponding apoptosis targets. Finally, experimental validation demonstrated that DHI treatment significantly increased the Bcl-2 level and suppressed DOX-induced Bax and caspase-3 expression in rat heart tissue. Furthermore, DHI treatment obviously decreased the apoptosis rate of DOX-treated H9c2 cells. These results indicate that DHI attenuated DOX-induced cardiotoxicity via regulating the apoptosis pathway. The present study suggested that DHI is a promising agent for the prevention of DOX-induced cardiotoxicity.
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spelling pubmed-94415492022-09-06 Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation Yi, Xiaojiao Wang, Fugen Feng, Yan Zhu, Junfeng Wu, Yongjiang Front Pharmacol Pharmacology Doxorubicin (DOX) is a potent chemotherapeutic agent that is used against various types of human malignancies. However, the associated risk of cardiotoxicity has limited its clinical application. Danhong injection (DHI) is a Chinese medicine with multiple pharmacological activities and is widely used for treating cardiovascular diseases. The aim of the present study was to evaluate the potential protective effect of DHI on DOX-induced cardiotoxicity in vivo and to investigate the possible underlying mechanisms. First, a sensitive and reliable HPLC−ESI-Q-TOF-MS/MS method was developed to comprehensively analyze the chemical compositions of DHI. A total of 56 compounds were identified, including phenolic acids, tanshinones, and flavonoids. Then, a DOX-induced chronic cardiotoxicity rat model was established to assess the therapeutic effect of DHI. As a result, DHI administration prevented the reduction in body weight and heart weight, and improved electrocardiogram performance. Additionally, the elevated levels of serum biochemical indicators were reduced, and the activities of oxidative enzymes were restored in the DOX-DHI group. Network pharmacology analysis further revealed that these effects might be attributed to 14 active compounds (e.g., danshensu, salvianolic acid A, salvianolic acid B, rosmarinic acid, and tanshinone IIA) and 15 potential targets (e.g., CASP3, SOD1, NOS3, TNF, and TOP2A). The apoptosis pathway was highly enriched according to the KEGG analysis. Molecular docking verified the good binding affinities between the active compounds and the corresponding apoptosis targets. Finally, experimental validation demonstrated that DHI treatment significantly increased the Bcl-2 level and suppressed DOX-induced Bax and caspase-3 expression in rat heart tissue. Furthermore, DHI treatment obviously decreased the apoptosis rate of DOX-treated H9c2 cells. These results indicate that DHI attenuated DOX-induced cardiotoxicity via regulating the apoptosis pathway. The present study suggested that DHI is a promising agent for the prevention of DOX-induced cardiotoxicity. Frontiers Media S.A. 2022-08-22 /pmc/articles/PMC9441549/ /pubmed/36071840 http://dx.doi.org/10.3389/fphar.2022.929302 Text en Copyright © 2022 Yi, Wang, Feng, Zhu and Wu. 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
Yi, Xiaojiao
Wang, Fugen
Feng, Yan
Zhu, Junfeng
Wu, Yongjiang
Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
title Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
title_full Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
title_fullStr Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
title_full_unstemmed Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
title_short Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
title_sort danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441549/
https://www.ncbi.nlm.nih.gov/pubmed/36071840
http://dx.doi.org/10.3389/fphar.2022.929302
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