Format

Send to

Choose Destination
Mol Nutr Food Res. 2017 Sep;61(9). doi: 10.1002/mnfr.201600966. Epub 2017 Jun 12.

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

Author information

1
Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China.
2
Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
3
Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.

Abstract

SCOPE:

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.

METHODS AND RESULTS:

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).

CONCLUSION:

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.

KEYWORDS:

Atherosclerosis; Autophagy; Inflammation; Morin hydrate; cAMP-PKA-AMPK-SIRT1 signaling pathway

PMID:
28421659
DOI:
10.1002/mnfr.201600966
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center