Cargando…
The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology
Astragaloside IV (AS-IV) has been used to treat cardiovascular disease. However, whether AS-IV exerts a protective effect against hypertensive heart disease has not been investigated. This study aimed to investigate the antihypertensive and cardioprotective effects of AS-IV on L-NAME-induced hyperte...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602690/ https://www.ncbi.nlm.nih.gov/pubmed/34803698 http://dx.doi.org/10.3389/fphar.2021.755653 |
_version_ | 1784601623675273216 |
---|---|
author | Jing, Haoran Xie, Rongsheng Bai, Yu Duan, Yuchen Sun, Chongyang Wang, Ye Cao, Rongyi Ling, Zaisheng Qu, Xiufen |
author_facet | Jing, Haoran Xie, Rongsheng Bai, Yu Duan, Yuchen Sun, Chongyang Wang, Ye Cao, Rongyi Ling, Zaisheng Qu, Xiufen |
author_sort | Jing, Haoran |
collection | PubMed |
description | Astragaloside IV (AS-IV) has been used to treat cardiovascular disease. However, whether AS-IV exerts a protective effect against hypertensive heart disease has not been investigated. This study aimed to investigate the antihypertensive and cardioprotective effects of AS-IV on L-NAME-induced hypertensive rats via network pharmacology and experimental pharmacology. The network pharmacology and bioinformatics analyses were performed to obtain the potential targets of AS-IV and hypertensive heart disease. The rat hypertension model was established by administrated 50 mg/kg/day of L-NAME for 5 weeks. Meanwhile, hypertension rats were intragastrically administrated with vehicle or AS-IV or fosinopril for 5 weeks. Cardiovascular parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rates, and body weight), cardiac function parameters (LVEDd, LVEDs, and fractional shortening), cardiac marker enzymes (creatine kinase, CK-MB, and lactate dehydrogenase), cardiac hypertrophy markers (atrial natriuretic peptide and brain natriuretic peptide), endothelial function biomarkers (nitric oxide and eNOS), inflammation biomarkers (IL-6 and TNF-α) and oxidative stress biomarkers (SOD, MDA, and GSH) were measured and cardiac tissue histology performed. Network pharmacological analysis screened the top 20 key genes in the treatment of hypertensive heart disease treated with AS-IV. Besides, AS-IV exerted a beneficial effect on cardiovascular and cardiac function parameters. Moreover, AS-IV alleviated cardiac hypertrophy via down-regulating the expression of ANP and BNP and improved histopathology changes of cardiac tissue. AS-IV improved endothelial function via the up-regulation of eNOS expression, alleviated oxidative stress via increasing antioxidant enzymes activities, and inhibited cardiac inflammation via down-regulating IL-6 and TNF-α expression. Our findings suggested that AS-IV is a potential therapeutic drug to improve L-NAME-induced hypertensive heart disease partly mediated via modulation of eNOS and oxidative stress. |
format | Online Article Text |
id | pubmed-8602690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86026902021-11-20 The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology Jing, Haoran Xie, Rongsheng Bai, Yu Duan, Yuchen Sun, Chongyang Wang, Ye Cao, Rongyi Ling, Zaisheng Qu, Xiufen Front Pharmacol Pharmacology Astragaloside IV (AS-IV) has been used to treat cardiovascular disease. However, whether AS-IV exerts a protective effect against hypertensive heart disease has not been investigated. This study aimed to investigate the antihypertensive and cardioprotective effects of AS-IV on L-NAME-induced hypertensive rats via network pharmacology and experimental pharmacology. The network pharmacology and bioinformatics analyses were performed to obtain the potential targets of AS-IV and hypertensive heart disease. The rat hypertension model was established by administrated 50 mg/kg/day of L-NAME for 5 weeks. Meanwhile, hypertension rats were intragastrically administrated with vehicle or AS-IV or fosinopril for 5 weeks. Cardiovascular parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rates, and body weight), cardiac function parameters (LVEDd, LVEDs, and fractional shortening), cardiac marker enzymes (creatine kinase, CK-MB, and lactate dehydrogenase), cardiac hypertrophy markers (atrial natriuretic peptide and brain natriuretic peptide), endothelial function biomarkers (nitric oxide and eNOS), inflammation biomarkers (IL-6 and TNF-α) and oxidative stress biomarkers (SOD, MDA, and GSH) were measured and cardiac tissue histology performed. Network pharmacological analysis screened the top 20 key genes in the treatment of hypertensive heart disease treated with AS-IV. Besides, AS-IV exerted a beneficial effect on cardiovascular and cardiac function parameters. Moreover, AS-IV alleviated cardiac hypertrophy via down-regulating the expression of ANP and BNP and improved histopathology changes of cardiac tissue. AS-IV improved endothelial function via the up-regulation of eNOS expression, alleviated oxidative stress via increasing antioxidant enzymes activities, and inhibited cardiac inflammation via down-regulating IL-6 and TNF-α expression. Our findings suggested that AS-IV is a potential therapeutic drug to improve L-NAME-induced hypertensive heart disease partly mediated via modulation of eNOS and oxidative stress. Frontiers Media S.A. 2021-11-05 /pmc/articles/PMC8602690/ /pubmed/34803698 http://dx.doi.org/10.3389/fphar.2021.755653 Text en Copyright © 2021 Jing, Xie, Bai, Duan, Sun, Wang, Cao, Ling and Qu. 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 Jing, Haoran Xie, Rongsheng Bai, Yu Duan, Yuchen Sun, Chongyang Wang, Ye Cao, Rongyi Ling, Zaisheng Qu, Xiufen The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology |
title | The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology |
title_full | The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology |
title_fullStr | The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology |
title_full_unstemmed | The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology |
title_short | The Mechanism Actions of Astragaloside IV Prevents the Progression of Hypertensive Heart Disease Based on Network Pharmacology and Experimental Pharmacology |
title_sort | mechanism actions of astragaloside iv prevents the progression of hypertensive heart disease based on network pharmacology and experimental pharmacology |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602690/ https://www.ncbi.nlm.nih.gov/pubmed/34803698 http://dx.doi.org/10.3389/fphar.2021.755653 |
work_keys_str_mv | AT jinghaoran themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT xierongsheng themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT baiyu themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT duanyuchen themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT sunchongyang themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT wangye themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT caorongyi themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT lingzaisheng themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT quxiufen themechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT jinghaoran mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT xierongsheng mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT baiyu mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT duanyuchen mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT sunchongyang mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT wangye mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT caorongyi mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT lingzaisheng mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology AT quxiufen mechanismactionsofastragalosideivpreventstheprogressionofhypertensiveheartdiseasebasedonnetworkpharmacologyandexperimentalpharmacology |