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3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway

3,4′,5-trimethoxy-trans-stilbene (TMS) is a methoxylated derivative of resveratrol. Previous studies showed the vaso-protective effects of resveratrol; nevertheless, research on this derivative is scarce. The current study aimed to explore whether TMS can alleviate endothelial dysfunction in diabeti...

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Autores principales: Zhou, Chunxiu, Tan, Yi, Xu, Baojun, Wang, Yitao, Cheang, Wai-San
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311592/
https://www.ncbi.nlm.nih.gov/pubmed/35883777
http://dx.doi.org/10.3390/antiox11071286
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author Zhou, Chunxiu
Tan, Yi
Xu, Baojun
Wang, Yitao
Cheang, Wai-San
author_facet Zhou, Chunxiu
Tan, Yi
Xu, Baojun
Wang, Yitao
Cheang, Wai-San
author_sort Zhou, Chunxiu
collection PubMed
description 3,4′,5-trimethoxy-trans-stilbene (TMS) is a methoxylated derivative of resveratrol. Previous studies showed the vaso-protective effects of resveratrol; nevertheless, research on this derivative is scarce. The current study aimed to explore whether TMS can alleviate endothelial dysfunction in diabetic and obese mice, along with the underlying mechanisms. Thoracic aortas isolated from male C57BL/6J mice and primary cultures of rat aortic endothelial cells were treated with high glucose with or without TMS. High glucose exposure impaired acetylcholine-induced endothelium-dependent relaxations, down-regulated NO bioavailability and the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1)/endothelial nitric oxide synthase (eNOS) pathway, increased endoplasmic reticulum (ER) stress and oxidative stress, which were reversed by TMS treatment. Moreover, the protective effects of TMS were abolished by Compound C (AMPK inhibitor), and EX527 (SIRT1 inhibitor). The mice were fed with high-fat diet (60% kcal% fat) for 14 weeks to establish a diabetic and obese model, and were orally administered TMS (10 mg/kg/day) in the last 4 weeks. Chronic TMS treatment alleviated endothelial dysfunction via enhancing the AMPK/SIRT1/eNOS pathway and attenuated oxidative stress and ER stress in aortas of diet-induced obese mice. In summary, our study reveals the potent vaso-protective effect of TMS and its therapeutic potential against endothelial dysfunction in metabolic disorders.
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spelling pubmed-93115922022-07-26 3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway Zhou, Chunxiu Tan, Yi Xu, Baojun Wang, Yitao Cheang, Wai-San Antioxidants (Basel) Article 3,4′,5-trimethoxy-trans-stilbene (TMS) is a methoxylated derivative of resveratrol. Previous studies showed the vaso-protective effects of resveratrol; nevertheless, research on this derivative is scarce. The current study aimed to explore whether TMS can alleviate endothelial dysfunction in diabetic and obese mice, along with the underlying mechanisms. Thoracic aortas isolated from male C57BL/6J mice and primary cultures of rat aortic endothelial cells were treated with high glucose with or without TMS. High glucose exposure impaired acetylcholine-induced endothelium-dependent relaxations, down-regulated NO bioavailability and the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1)/endothelial nitric oxide synthase (eNOS) pathway, increased endoplasmic reticulum (ER) stress and oxidative stress, which were reversed by TMS treatment. Moreover, the protective effects of TMS were abolished by Compound C (AMPK inhibitor), and EX527 (SIRT1 inhibitor). The mice were fed with high-fat diet (60% kcal% fat) for 14 weeks to establish a diabetic and obese model, and were orally administered TMS (10 mg/kg/day) in the last 4 weeks. Chronic TMS treatment alleviated endothelial dysfunction via enhancing the AMPK/SIRT1/eNOS pathway and attenuated oxidative stress and ER stress in aortas of diet-induced obese mice. In summary, our study reveals the potent vaso-protective effect of TMS and its therapeutic potential against endothelial dysfunction in metabolic disorders. MDPI 2022-06-28 /pmc/articles/PMC9311592/ /pubmed/35883777 http://dx.doi.org/10.3390/antiox11071286 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Chunxiu
Tan, Yi
Xu, Baojun
Wang, Yitao
Cheang, Wai-San
3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway
title 3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway
title_full 3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway
title_fullStr 3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway
title_full_unstemmed 3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway
title_short 3,4′,5-Trimethoxy-trans-stilbene Alleviates Endothelial Dysfunction in Diabetic and Obese Mice via Activation of the AMPK/SIRT1/eNOS Pathway
title_sort 3,4′,5-trimethoxy-trans-stilbene alleviates endothelial dysfunction in diabetic and obese mice via activation of the ampk/sirt1/enos pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311592/
https://www.ncbi.nlm.nih.gov/pubmed/35883777
http://dx.doi.org/10.3390/antiox11071286
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