Cargando…
Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling
Left ventricular hypertrophy (LVH) is an important characteristic of hypertensive heart disease. Renin-angiotensin system (RAS) blockers have been shown to be effective drugs for the reversal of LVH. Clinical and experimental studies have shown that Zi Shen Huo Luo Formula (ZSHLF) can improve the ef...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147343/ https://www.ncbi.nlm.nih.gov/pubmed/32317965 http://dx.doi.org/10.3389/fphar.2020.00383 |
_version_ | 1783520400603348992 |
---|---|
author | Song, Xiaotong Zhao, Yue Wang, Shijun Wang, Yuan Chen, Qian Zhao, Haijun Wang, Hua Tian, Sheng Yu, Huayun Wu, Zhichun |
author_facet | Song, Xiaotong Zhao, Yue Wang, Shijun Wang, Yuan Chen, Qian Zhao, Haijun Wang, Hua Tian, Sheng Yu, Huayun Wu, Zhichun |
author_sort | Song, Xiaotong |
collection | PubMed |
description | Left ventricular hypertrophy (LVH) is an important characteristic of hypertensive heart disease. Renin-angiotensin system (RAS) blockers have been shown to be effective drugs for the reversal of LVH. Clinical and experimental studies have shown that Zi Shen Huo Luo Formula (ZSHLF) can improve the efficacy of perindopril in the treatment of hypertensive LVH, but its mechanism is unclear. This study aimed to investigate the possible mechanism to improve the efficacy of perindopril. First, we identified 23 compounds in ZSHLF by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis, among which ferulic acid, caffeic acid, vanillic acid, berberine, rutin, quercetin, kaempferol, stachydrine, and tiliroside have been reported to reduce blood pressure and exhibit cardioprotective effects. Second, we treated spontaneously hypertensive rats (SHRs) with perindopril and ZSHLF for 12 continuous weeks and found that chronic use of perindopril could increase the aldosterone (ALD) levels and cause aldosterone breakthrough (ABT). ZSHLF combined with perindopril reduced the ALD levels, interfered with ABT, decreased blood pressure, improved left ventricular diastolic dysfunction, and decreased the collagen volume fraction; these effects were superior to those of perindopril alone. In vitro experiments, ALD-induced cardiomyocytes (H9c2 cells) and cardiac fibroblasts were treated with ZSHLF-containing serum, which suppressed ALD-induced cardiomyocyte hypertrophy and cardiac fibroblast proliferation, increased mineralocorticoid receptor (MR) and Cav-1 colocalization and decreased phosphorylated epidermal growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase (pERK) protein expression the cells. In conclusion, ZSHLF can interfere with ABT and affect the pathological role of ALD by affecting MR and Cav-1 interactions and EGFR/ERK signaling pathway. These effects represent a possible mechanism by which ZSHLF improves the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive LVH treatment. However, the major bioactive components or metabolites responsible for the effects and the implications of these findings in patients need further verification. |
format | Online Article Text |
id | pubmed-7147343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71473432020-04-21 Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling Song, Xiaotong Zhao, Yue Wang, Shijun Wang, Yuan Chen, Qian Zhao, Haijun Wang, Hua Tian, Sheng Yu, Huayun Wu, Zhichun Front Pharmacol Pharmacology Left ventricular hypertrophy (LVH) is an important characteristic of hypertensive heart disease. Renin-angiotensin system (RAS) blockers have been shown to be effective drugs for the reversal of LVH. Clinical and experimental studies have shown that Zi Shen Huo Luo Formula (ZSHLF) can improve the efficacy of perindopril in the treatment of hypertensive LVH, but its mechanism is unclear. This study aimed to investigate the possible mechanism to improve the efficacy of perindopril. First, we identified 23 compounds in ZSHLF by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis, among which ferulic acid, caffeic acid, vanillic acid, berberine, rutin, quercetin, kaempferol, stachydrine, and tiliroside have been reported to reduce blood pressure and exhibit cardioprotective effects. Second, we treated spontaneously hypertensive rats (SHRs) with perindopril and ZSHLF for 12 continuous weeks and found that chronic use of perindopril could increase the aldosterone (ALD) levels and cause aldosterone breakthrough (ABT). ZSHLF combined with perindopril reduced the ALD levels, interfered with ABT, decreased blood pressure, improved left ventricular diastolic dysfunction, and decreased the collagen volume fraction; these effects were superior to those of perindopril alone. In vitro experiments, ALD-induced cardiomyocytes (H9c2 cells) and cardiac fibroblasts were treated with ZSHLF-containing serum, which suppressed ALD-induced cardiomyocyte hypertrophy and cardiac fibroblast proliferation, increased mineralocorticoid receptor (MR) and Cav-1 colocalization and decreased phosphorylated epidermal growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase (pERK) protein expression the cells. In conclusion, ZSHLF can interfere with ABT and affect the pathological role of ALD by affecting MR and Cav-1 interactions and EGFR/ERK signaling pathway. These effects represent a possible mechanism by which ZSHLF improves the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive LVH treatment. However, the major bioactive components or metabolites responsible for the effects and the implications of these findings in patients need further verification. Frontiers Media S.A. 2020-04-03 /pmc/articles/PMC7147343/ /pubmed/32317965 http://dx.doi.org/10.3389/fphar.2020.00383 Text en Copyright © 2020 Song, Zhao, Wang, Wang, Chen, Zhao, Wang, Tian, Yu and Wu http://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 Song, Xiaotong Zhao, Yue Wang, Shijun Wang, Yuan Chen, Qian Zhao, Haijun Wang, Hua Tian, Sheng Yu, Huayun Wu, Zhichun Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling |
title | Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling |
title_full | Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling |
title_fullStr | Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling |
title_full_unstemmed | Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling |
title_short | Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling |
title_sort | zi shen huo luo formula enhances the therapeutic effects of angiotensin-converting enzyme inhibitors on hypertensive left ventricular hypertrophy by interfering with aldosterone breakthrough and affecting caveolin-1/mineralocorticoid receptor colocalization and downstream extracellular signal-regulated kinase signaling |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147343/ https://www.ncbi.nlm.nih.gov/pubmed/32317965 http://dx.doi.org/10.3389/fphar.2020.00383 |
work_keys_str_mv | AT songxiaotong zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT zhaoyue zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT wangshijun zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT wangyuan zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT chenqian zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT zhaohaijun zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT wanghua zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT tiansheng zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT yuhuayun zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi AT wuzhichun zishenhuoluoformulaenhancesthetherapeuticeffectsofangiotensinconvertingenzymeinhibitorsonhypertensiveleftventricularhypertrophybyinterferingwithaldosteronebreakthroughandaffectingcaveolin1mineralocorticoidreceptorcolocalizationanddownstreamextracellularsi |