Chlorogenic Acid Inhibits Inflammation And Oxidative Stress By Inhibiting TLR4/MAPK/NFκB Pathway And Activating Autophagy

Background and Objective:Cardiovascular disease is currently the leading cause of death in my country.Atherosclerosis is a cardiovascular disease with an increasing incidence worldwide.It is also the cause of cerebral infarction,peripheral vascular disease,coronary heart disease and so on.Inflammation,which accompanies the development of atherosclerosis,is a key factor in its formation.Oxidative stress is a concomitant reaction closely related to inflammation.Autophagy is a protective mechanism that maintains cell homeostasis and plays a role in inflammation.Chlorogenic acid is a polyphenolic compound with good anti-inflammatory and antioxidant properties.The incidence of atherosclerosis is increasing day by day,and it constitutes a serious social problem.Therefore,research on the prevention and control of atherosclerosis is of great significance.Inflammation is closely related to atherosclerosis.From the perspective of prevention and treatment of inflammation,this article explores the anti-inflammatory effects of chlorogenic acid,related mechanisms,and its relationship with oxidative stress and autophagy,so as to provide references for the prevention and control of atherosclerosis.Materials and Methods:The cell line studied in this paper is human umbilical vein endothelial cells.The effect of chlorogenic acid on cell viability was detected by MTT method.After treating the cells with lipopolysaccharide and chlorogenic acid,the expression changes of tumor necrosis factor α(TNF-α),interleukin 6(IL-6),Vascular cell adhesion molecule(VCAM),intercellular adhesion molecule-1(ICAM-1),cyclooxygenase-2(COX-2),matrix metalloproteinase-9(MMP-9)were detected by ELISA and Western Blot technology.And study the relevant pathways of its effect.Detect the expression changes of mitochondrial membrane potential,ROS,SOD,GSH,MDA by immunofluorescence and ELISA technology,and explore the influence on oxidative stress.Western Blot technology was used to detect the expression changes of P62 and MAP1LC3B-II to explore the relationship between chlorogenic acid and autophagy.Results:The results of MTT method showed that chlorogenic acid had no effect on the cell viability of human umbilical vein endothelial cells.Chlorogenic acid inhibited TNF-α and IL-6 in a dose-dependent manner while inhibiting the expression of VCAM,ICAM-1,COX-2,and MMP-9 in a dose-and time-dependent manner.And chlorogenic acid significantly inhibited the expression of related proteins in the TLR4/MAPK/NF-κB signaling pathway.Chlorogenic acid significantly reduced the expression of ROS and MDA and enhanced the expression of mitochondrial membrane potential,SOD and GSH.In the study of chlorogenic acid and autophagy,chlorogenic acid enhanced MAP1LC3B-II and decreased the expression of P62.It is worth mentioning that chlorogenic acid inhibits the NF-κB pathway while activating autophagy.When 3-methyladenine(3-MA)is used to inhibit autophagy,the expressions of VCAM,ICAM-1,COX-2,and MMP-9 are significantly enhanced,which relieves the anti-inflammatory effect of chlorogenic acid.Conclusion:1.Chlorogenic acid inhibits the inflammatory response and oxidative stress induced by lipopolysaccharide in human umbilical vein endothelial cells.2.Chlorogenic acid stimulates autophagy by inhibiting the NF-κB pathway.3.Chlorogenic acid activates autophagy by inhibiting the TLR4/MAPK/NF-κB signaling pathway,thereby inhibiting inflammation and oxidative stress.