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Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice

PURPOSE: In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of db/db diabetic mice. METHODS: Twenty healthy male db/db mice aged 8 weeks were randomly divided into db/db+ECH (n=10, ECH, 300 mg/(kg/d)),...

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Autores principales: Zhang, Xiang, Hao, Yarong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755380/
https://www.ncbi.nlm.nih.gov/pubmed/33376302
http://dx.doi.org/10.2147/DDDT.S276972
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author Zhang, Xiang
Hao, Yarong
author_facet Zhang, Xiang
Hao, Yarong
author_sort Zhang, Xiang
collection PubMed
description PURPOSE: In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of db/db diabetic mice. METHODS: Twenty healthy male db/db mice aged 8 weeks were randomly divided into db/db+ECH (n=10, ECH, 300 mg/(kg/d)), db/db (n=10, saline), and db/m control groups (n=9). Mice were monitored weekly for diet and activity. Mice were injected with 2% of pentobarbital sodium in week 10 and executed. Weight and free blood glucose (FBG) were measured weekly. Echocardiographs were used to detect cardiac function. HE staining, Sudan II staining, Masson’s trichrome staining and Tunel assays were used to evaluate myocardial tissue pathological changes, collagen fiber deposition, lipid accumulation and apoptosis rates in cardiomyocytes, respectively. Western blot and RT-PCR analysis were used to detect the expression of components of the PPAR-α/M-CPT-1 and p53/p38MAPK signaling axis. RESULTS: Compared to db/db mice, ECH groups showed lower blood glucose and lipid levels. Deterioration in cardiac function was also delayed following ECH treatment. Histopathological analysis showed that ECH significantly improved myocardial tissue in db/db mice, including reduced intercellular spaces, regular arrangements, improved extracellular matrix deposition, and reduced lipid accumulation. ECH also significantly reduced oxidative stress levels in myocardial tissue in db/db mice. Moreover, ECH inhibited PPAR-α/M-CPT-1 signaling, downregulated CD36, and upregulated glucose transporter type 4 (GLUT-4) expression in db/db mouse models of DCM. ECH also inhibited p53/p38MAPK signaling, downregulated caspase-3 and caspase-8, and upregulated Bcl-2/Bax in db/db mouse models of DCM. CONCLUSION: ECH displays protective effects in DCM, including the inhibition of cardiac apoptosis and oxidative stress, and improved lipid metabolism in cardiomyocytes. ECH also inhibits cardiac apoptosis through its regulation of p53/p38MAPK signaling, and prevents lipid accumulation through suppression of the PPAR-α/M-CPT-1 signaling axis.
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spelling pubmed-77553802020-12-28 Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice Zhang, Xiang Hao, Yarong Drug Des Devel Ther Original Research PURPOSE: In this study, we investigated the protective effects and mechanism of action of echinacoside (ECH) from cistanche tubulosa extract in cardiomyocytes of db/db diabetic mice. METHODS: Twenty healthy male db/db mice aged 8 weeks were randomly divided into db/db+ECH (n=10, ECH, 300 mg/(kg/d)), db/db (n=10, saline), and db/m control groups (n=9). Mice were monitored weekly for diet and activity. Mice were injected with 2% of pentobarbital sodium in week 10 and executed. Weight and free blood glucose (FBG) were measured weekly. Echocardiographs were used to detect cardiac function. HE staining, Sudan II staining, Masson’s trichrome staining and Tunel assays were used to evaluate myocardial tissue pathological changes, collagen fiber deposition, lipid accumulation and apoptosis rates in cardiomyocytes, respectively. Western blot and RT-PCR analysis were used to detect the expression of components of the PPAR-α/M-CPT-1 and p53/p38MAPK signaling axis. RESULTS: Compared to db/db mice, ECH groups showed lower blood glucose and lipid levels. Deterioration in cardiac function was also delayed following ECH treatment. Histopathological analysis showed that ECH significantly improved myocardial tissue in db/db mice, including reduced intercellular spaces, regular arrangements, improved extracellular matrix deposition, and reduced lipid accumulation. ECH also significantly reduced oxidative stress levels in myocardial tissue in db/db mice. Moreover, ECH inhibited PPAR-α/M-CPT-1 signaling, downregulated CD36, and upregulated glucose transporter type 4 (GLUT-4) expression in db/db mouse models of DCM. ECH also inhibited p53/p38MAPK signaling, downregulated caspase-3 and caspase-8, and upregulated Bcl-2/Bax in db/db mouse models of DCM. CONCLUSION: ECH displays protective effects in DCM, including the inhibition of cardiac apoptosis and oxidative stress, and improved lipid metabolism in cardiomyocytes. ECH also inhibits cardiac apoptosis through its regulation of p53/p38MAPK signaling, and prevents lipid accumulation through suppression of the PPAR-α/M-CPT-1 signaling axis. Dove 2020-12-18 /pmc/articles/PMC7755380/ /pubmed/33376302 http://dx.doi.org/10.2147/DDDT.S276972 Text en © 2020 Zhang and Hao. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhang, Xiang
Hao, Yarong
Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice
title Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice
title_full Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice
title_fullStr Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice
title_full_unstemmed Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice
title_short Beneficial Effects of Echinacoside on Diabetic Cardiomyopathy in Diabetic Db/Db Mice
title_sort beneficial effects of echinacoside on diabetic cardiomyopathy in diabetic db/db mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755380/
https://www.ncbi.nlm.nih.gov/pubmed/33376302
http://dx.doi.org/10.2147/DDDT.S276972
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