Morin Hydrate Inhibits Lipopolysaccharide-induced Inflammatory Responses By Inhibiting The Activation Of The PI3K/Akt1/NF?B Signaling Pathway In An Autophagy-Dependent Pathway In Endothelial Cells

Chronic inflammation of the long-term accumulation of blood vessel walls causes atherosclerosis(AS).Inflammation involves all the aspects of the process and is characterized by the increased expression of adhesion molecules.Morin hydrate(MO)is a bioflavonoid compound with positive anti-inflammatory effects.Although the exact mechanism has not been fully elucidated,there is evidence that it has various beneficial pharmacological effects.Autophagy denotes the degradation process of intracellular proteins and organelles,which has a protective effect on some inflammatory damage.Therefore,it is aimed to explore the anti-inflammatory effects of MO in human umbilical vein endothelial cells(HUVECs)and its relation with autophagy.It was found that MO could inhibit lipopolysaccharide(LPS)-induced ICAM-1(intercellular adhesion molecule-1),VCAM-1(vascular cell adhesion molecule-1),COX-2(prostaglandin-endoperoxide synthase 2),and MMP-9(matrix metallopeptidase 9)levels in HUVECs in an MO dose-and time-dependent manners and the expression of TNF-?(tumor necrosis factor alpha)and IL-6(interleukin-6)in an MO dose-dependent manner by inhibiting the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/NF?B activation.Further,we found that this anti-inflammatory effect of MO was achieved by an autophagy-dependent pathway.When autophagy was inhibited by 3-MA(3-methyladenine)or siRNA,the anti-inflammatory effect of MO disappeared.The relation between MO and autophagy was further explored;it was found that MO induces autophagy in normal HUVECs and LPS-stimulated HUVECs by inhibiting the NF?B signaling pathway.In conclusion,MO inhibits LPS-induced inflammatory responses by inhibiting the activation of the PI3K/Akt1/NF?B signaling pathway in an autophagy-dependent pathway in HUVECs,and MO could activate autophagy by inhibiting the NF?B signaling pathway.