The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated with autophagy induction through cAMP signaling

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.

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Official URL: http://dx.doi.org/10.1002/mnfr.201600966

Abstract

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. This study investigated the effect of MO in atherosclerosis in ApoE-/- 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). 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
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:	19 Jan 2023 06:59
DOI:	10.1002/mnfr.201600966
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008422