Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling

Background: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. Cyclocarya paliurus is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether C. paliurus leaves can prevent or treat DCM, however, it remai...

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Main Authors: Yang Wang, Xiaojie Zheng, Longyu Li, Hong Wang, Keyuan Chen, Mingjie Xu, Yiwei Wu, Xueli Huang, Meiling Zhang, Xiaoxia Ye, Tunhai Xu, Rongchang Chen, Yindi Zhu
Format: Article
Language:English
Published: Swedish Nutrition Foundation 2020-08-01
Series:Food & Nutrition Research
Subjects:
Online Access:https://foodandnutritionresearch.net/index.php/fnr/article/view/4267/11166
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author Yang Wang
Xiaojie Zheng
Longyu Li
Hong Wang
Keyuan Chen
Mingjie Xu
Yiwei Wu
Xueli Huang
Meiling Zhang
Xiaoxia Ye
Tunhai Xu
Rongchang Chen
Yindi Zhu
author_facet Yang Wang
Xiaojie Zheng
Longyu Li
Hong Wang
Keyuan Chen
Mingjie Xu
Yiwei Wu
Xueli Huang
Meiling Zhang
Xiaoxia Ye
Tunhai Xu
Rongchang Chen
Yindi Zhu
author_sort Yang Wang
collection DOAJ
description Background: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. Cyclocarya paliurus is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether C. paliurus leaves can prevent or treat DCM, however, it remains to be formally assessed. The present study was therefore designed to assess the ability of C. paliurus to protect against DCM in db/db mice. Methods: Male wild-type (WT) and db/db mice were administered C. paliurus ethanol leaf extracts (ECL) or appropriate vehicle controls daily via gavage, and levels of blood glucose in treated animals were assessed on a weekly basis. After a 10-week treatment, the levels of cardiac troponin I (cTn-I), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), total triglycerides (TG), and total cholesterol (TC) in serum were measured. Activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in heart tissues were detected. Hematoxylin-eosin (HE) and Masson staining were conducted. The protein expression that related with oxidative stress and inflammatory reaction was evaluated by Western blotting. Results: Compared with WT mice, the TG, TC, and blood glucose levels in db/db mice increased significantly, which were reduced by ECL treatment. Compared with WT mice, the levels of LDH, CK-MB, AST, and cTn-I in serum and MDA in heart tissues of db/db mice increased significantly. Activities of SOD, GSH-Px, and CAT in heart tissues of db/db mice decreased significantly. The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in heart tissues of db/db mice increased remarkably. However, ECL treatment improved the above pathological changes significantly. ECL alleviated pathological injury and fibrosis in heart tissues of mice. Western blotting showed that ECL increased Bcl-2 level and decreased Bax, cle-caspase-3, and cle-caspase-9 expression. Furthermore, ECL inhibited NF-κB nuclear translocation and increased PI3K and p-Akt expressions. Conclusion: Our results indicate that ECL treatment can markedly reduce pathological cardiac damage in db/db mice through antiapoptotic, antifibrotic, and anti-inflammatory mechanisms. Specifically, this extract was able to suppress NF-κB activation via the PI3K/Akt signaling pathway. Given its diverse activities and lack of significant side effects, ECL may thus have therapeutic value for the treatment of DCM.
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spelling doaj.art-56c637a13d4d4b93aae834b7122b6a5e2022-12-22T01:29:28ZengSwedish Nutrition FoundationFood & Nutrition Research1654-661X2020-08-0164011210.29219/fnr.v64.42674267Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signalingYang Wang0Xiaojie Zheng1Longyu Li2Hong Wang3Keyuan Chen4Mingjie Xu5Yiwei Wu6Xueli Huang7Meiling Zhang8Xiaoxia Ye9Tunhai Xu10Rongchang Chen11Yindi Zhu12School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaWenzhou Vocational College of Science & Technology, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Quality Research, Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaBackground: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. Cyclocarya paliurus is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether C. paliurus leaves can prevent or treat DCM, however, it remains to be formally assessed. The present study was therefore designed to assess the ability of C. paliurus to protect against DCM in db/db mice. Methods: Male wild-type (WT) and db/db mice were administered C. paliurus ethanol leaf extracts (ECL) or appropriate vehicle controls daily via gavage, and levels of blood glucose in treated animals were assessed on a weekly basis. After a 10-week treatment, the levels of cardiac troponin I (cTn-I), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), total triglycerides (TG), and total cholesterol (TC) in serum were measured. Activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in heart tissues were detected. Hematoxylin-eosin (HE) and Masson staining were conducted. The protein expression that related with oxidative stress and inflammatory reaction was evaluated by Western blotting. Results: Compared with WT mice, the TG, TC, and blood glucose levels in db/db mice increased significantly, which were reduced by ECL treatment. Compared with WT mice, the levels of LDH, CK-MB, AST, and cTn-I in serum and MDA in heart tissues of db/db mice increased significantly. Activities of SOD, GSH-Px, and CAT in heart tissues of db/db mice decreased significantly. The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in heart tissues of db/db mice increased remarkably. However, ECL treatment improved the above pathological changes significantly. ECL alleviated pathological injury and fibrosis in heart tissues of mice. Western blotting showed that ECL increased Bcl-2 level and decreased Bax, cle-caspase-3, and cle-caspase-9 expression. Furthermore, ECL inhibited NF-κB nuclear translocation and increased PI3K and p-Akt expressions. Conclusion: Our results indicate that ECL treatment can markedly reduce pathological cardiac damage in db/db mice through antiapoptotic, antifibrotic, and anti-inflammatory mechanisms. Specifically, this extract was able to suppress NF-κB activation via the PI3K/Akt signaling pathway. Given its diverse activities and lack of significant side effects, ECL may thus have therapeutic value for the treatment of DCM.https://foodandnutritionresearch.net/index.php/fnr/article/view/4267/11166cyclocarya paliurusdiabetic cardiomyopathyinflammationpi3k/aktnf-κb
spellingShingle Yang Wang
Xiaojie Zheng
Longyu Li
Hong Wang
Keyuan Chen
Mingjie Xu
Yiwei Wu
Xueli Huang
Meiling Zhang
Xiaoxia Ye
Tunhai Xu
Rongchang Chen
Yindi Zhu
Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling
Food & Nutrition Research
cyclocarya paliurus
diabetic cardiomyopathy
inflammation
pi3k/akt
nf-κb
title Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling
title_full Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling
title_fullStr Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling
title_full_unstemmed Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling
title_short Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling
title_sort cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db db mice via regulating pi3k akt nf κb signaling
topic cyclocarya paliurus
diabetic cardiomyopathy
inflammation
pi3k/akt
nf-κb
url https://foodandnutritionresearch.net/index.php/fnr/article/view/4267/11166
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