Cyclocarya paliurus Triterpenoids Improve Diabetes-Induced Hepatic Inflammation via the Rho-Kinase-Dependent Pathway.
Journal: 2019/August - Frontiers in Pharmacology
ISSN: 1663-9812
Abstract:
This study aimed to assess the effects of triterpene extract of Cyclocarya paliurus (Batal.) Iljinskaja (CPT) on diabetes-induced hepatic inflammation and to unveil the underlying mechanisms. Diabetes in db/db mice was alleviated after CPT administration, as assessed by the oral glucose tolerance test. In addition, treatment with CPT dramatically reduced serum insulin, aspartate amino-transaminase, alanine aminotransferase, triglyceride, and total cholesterol amounts. Besides, serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also reduced after CPT administration. Western blot analysis revealed that CPT treatment significantly reversed the protein expression levels of Rho, ROCK1, ROCK2, p-P65, p-IκBα, p-IKKα, and p-IKKβ in liver samples obtained from db/db mice. Upon palmitic acid stimulation, the protective effects of CPT on the liver were further assessed in HepG2 and LO2 cells, and no appreciable cytotoxic effects were found. Therefore, these findings indicate that CPT alleviates liver inflammation via Rho-kinase signaling. Chemical compounds evaluated in this report: Metformin (PubChem CID: 4091); Fasudil (PubChem CID: 3547); Palmitic acid (PubChem CID: 985).
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Front Pharmacol 10: 811

<em>Cyclocarya paliurus</em> Triterpenoids Improve Diabetes-Induced Hepatic Inflammation <em>via</em> the Rho-Kinase-Dependent Pathway

Figure S1

CPT’s effects on the Rho-kinase pathway in palmitic acid–treated LO2 cells. Data are mean ± SD. p<0.01, P<0.05 vs. control cells. **p<0.01, *p<0.05 vs. palmitic acid group.

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Figure S2

Graphical abstract of the manuscript.

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Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Edited by: Haitao Lu, Shanghai Jiao Tong University, China
Reviewed by: Geng Wenye, Fudan University, China; Chen Ling, University of Florida, United States
*Correspondence: Jian Zhang, moc.mctasj@naijgnahz; Shiping Ma, nc.ude.upc@amps
This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology
Edited by: Haitao Lu, Shanghai Jiao Tong University, China
Reviewed by: Geng Wenye, Fudan University, China; Chen Ling, University of Florida, United States
Received 2018 Nov 7; Accepted 2019 Jun 24.
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.

Abstract

This study aimed to assess the effects of triterpene extract of Cyclocarya paliurus (Batal.) Iljinskaja (CPT) on diabetes-induced hepatic inflammation and to unveil the underlying mechanisms. Diabetes in db/db mice was alleviated after CPT administration, as assessed by the oral glucose tolerance test. In addition, treatment with CPT dramatically reduced serum insulin, aspartate amino-transaminase, alanine aminotransferase, triglyceride, and total cholesterol amounts. Besides, serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also reduced after CPT administration. Western blot analysis revealed that CPT treatment significantly reversed the protein expression levels of Rho, ROCK1, ROCK2, p-P65, p-IκBα, p-IKKα, and p-IKKβ in liver samples obtained from db/db mice. Upon palmitic acid stimulation, the protective effects of CPT on the liver were further assessed in HepG2 and LO2 cells, and no appreciable cytotoxic effects were found. Therefore, these findings indicate that CPT alleviates liver inflammation via Rho-kinase signaling.

Chemical compounds evaluated in this report: Metformin (PubChem CID: 4091); Fasudil (PubChem CID: 3547); Palmitic acid (PubChem CID: 985).

Keywords: Cyclocarya paliurus, triterpene, diabetes mellitus, hepatic inflammation, ROCK, NF-κB
Abstract
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