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Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway

Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular functio...

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Autores principales: Jin, Sun Woo, Pham, Hoa Thi, Choi, Jae Ho, Lee, Gi Ho, Han, Eun Hee, Cho, Young Ho, Chung, Young Chul, Kim, Young Ho, Jeong, Hye Gwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888592/
https://www.ncbi.nlm.nih.gov/pubmed/31744135
http://dx.doi.org/10.3390/ijms20225772
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author Jin, Sun Woo
Pham, Hoa Thi
Choi, Jae Ho
Lee, Gi Ho
Han, Eun Hee
Cho, Young Ho
Chung, Young Chul
Kim, Young Ho
Jeong, Hye Gwang
author_facet Jin, Sun Woo
Pham, Hoa Thi
Choi, Jae Ho
Lee, Gi Ho
Han, Eun Hee
Cho, Young Ho
Chung, Young Chul
Kim, Young Ho
Jeong, Hye Gwang
author_sort Jin, Sun Woo
collection PubMed
description Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from Acanthopanax koreanum, acts as an enhancer of eNOS activity and NO production. IPA treatment induced eNOS phosphorylation and NO production, which was correlated with eNOS phosphorylation via the activation of JNK1/2, p38 MAPK, AMPK, and CaMKII. In addition, the induction of eNOS phosphorylation by IPA was attenuated by pharmacological inhibitor of MAPKs, AMPK, and CaMKII. Finally, IPA treatment prevented the adhesion of TNF-α-induced monocytes to endothelial cells and suppressed the TNF-α-stimulated ICAM-1 expression via activation of NF-κB, while treatment with L-NAME, the NOS inhibitor, reversed the inhibitory effect of IPA on TNF-α-induced ICAM-1 expression via activation of NF-κB. Taken together, these findings show that IPA protects against TNF-α-induced vascular endothelium dysfunction through attenuation of the NF-κB pathway by activating eNOS/NO pathway in endothelial cells.
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spelling pubmed-68885922019-12-09 Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway Jin, Sun Woo Pham, Hoa Thi Choi, Jae Ho Lee, Gi Ho Han, Eun Hee Cho, Young Ho Chung, Young Chul Kim, Young Ho Jeong, Hye Gwang Int J Mol Sci Article Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from Acanthopanax koreanum, acts as an enhancer of eNOS activity and NO production. IPA treatment induced eNOS phosphorylation and NO production, which was correlated with eNOS phosphorylation via the activation of JNK1/2, p38 MAPK, AMPK, and CaMKII. In addition, the induction of eNOS phosphorylation by IPA was attenuated by pharmacological inhibitor of MAPKs, AMPK, and CaMKII. Finally, IPA treatment prevented the adhesion of TNF-α-induced monocytes to endothelial cells and suppressed the TNF-α-stimulated ICAM-1 expression via activation of NF-κB, while treatment with L-NAME, the NOS inhibitor, reversed the inhibitory effect of IPA on TNF-α-induced ICAM-1 expression via activation of NF-κB. Taken together, these findings show that IPA protects against TNF-α-induced vascular endothelium dysfunction through attenuation of the NF-κB pathway by activating eNOS/NO pathway in endothelial cells. MDPI 2019-11-16 /pmc/articles/PMC6888592/ /pubmed/31744135 http://dx.doi.org/10.3390/ijms20225772 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jin, Sun Woo
Pham, Hoa Thi
Choi, Jae Ho
Lee, Gi Ho
Han, Eun Hee
Cho, Young Ho
Chung, Young Chul
Kim, Young Ho
Jeong, Hye Gwang
Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
title Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
title_full Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
title_fullStr Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
title_full_unstemmed Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
title_short Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway
title_sort impressic acid, a lupane-type triterpenoid from acanthopanax koreanum, attenuates tnf-α-induced endothelial dysfunction via activation of enos/no pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888592/
https://www.ncbi.nlm.nih.gov/pubmed/31744135
http://dx.doi.org/10.3390/ijms20225772
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