Zhou, Yue, Cao, Zhan-Qi, Wang, Hong-Yuan, Cheng, Yan-Na, Yu, Lu-Gang ORCID: 0000-0001-9641-3712, Zhang, Xin-Ke, Sun, Yan and Guo, Xiu-Li
(2017)
The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated with autophagy induction through cAMP signaling.
MOLECULAR NUTRITION & FOOD RESEARCH, 61 (9).
p. 1600966.
ISSN 1613-4125, 1613-4133
Text
Guo Xioli-MS anti-inflammatory .pdf - Author Accepted Manuscript Download (508kB) |
Abstract
<h4>Scope</h4>Although the previous trials of inflammation have indicated that morin hydrate (MO) hold considerable promise, understanding the distinct mechanism of MO against inflammation remains a challenge.<h4>Methods and results</h4>This study investigated the effect of MO in atherosclerosis in ApoE<sup>-/-</sup> mice and underlying cell signaling of MO effect in inflammation in human umbilical vein endothelial cells (HUVECs). Administration of MO significantly reduced serum lipid level, inflammatory cytokines (TNF-α and ICAM-1), and atherosclerotic plaque formation in vivo. MO presence attenuated the expression of TNF-α-induced inflammatory cytokines (ICAM-1, COX-2, and MMP-9), and remarkably enhanced microtubule associated protein 1 light chain 3 beta 2 (MAP1LC3B2) expression and sequestosome 1 (SQSTM1/p62) degradation in HUVECs. These MO effects were significantly prevented by the presence of autophagic inhibitors, 3-methyladenine (3-MA), or chloroquine (CQ), as well as siRNA suppression of ATG5 and BECN1. MO increased intracellular cAMP levels and activated cAMP-PKA-AMPK-SIRT1 signaling in vivo and in vitro. These changes resulted in increased expression of autophagy-related protein MAP1LC3B2 and decreased secretion of inflammatory cytokines (ICAM-1, COX-2, and MMP-9).<h4>Conclusion</h4>Our results suggest that anti-AS and anti-inflammatory effects of MO are largely associated with its induction of autophagy through stimulation of cAMP-PKA-AMPK-SIRT1 signaling pathway.
Item Type: | Article |
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Uncontrolled Keywords: | Atherosclerosis, Autophagy, Inflammation, cAMP-PKA-AMPK-SIRT1 signaling pathway, Morin hydrate |
Depositing User: | Symplectic Admin |
Date Deposited: | 12 Jul 2017 08:55 |
Last Modified: | 06 Dec 2024 21:56 |
DOI: | 10.1002/mnfr.201600966 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3008422 |