Effect Of Chlorogenic Acid On Chronic Stress-Induced Liver Inflammation In Rats By Regulating RvD1-NF-κB Pathway

Chronic stress is an inevitable and important factor in animal husbandry.Long-term stress reactions will damage animal organisms and reduce animal production performance.It has been shown that chronic stress is associated with the onset and progression of many types of liver disease,and chronic stress disorder is often accompanied by inflammation.Therefore,the research on chronic stress leading to inflammatory reactions is of great significance to solving the chronic stress problem in animal production.Chlorogenic Acid(CGA)is a phenolic acid with a wide range of biological activities,which has been proven to have a good anti-inflammatory effect.As an unsaturated fat derivative,Resolvin D1 plays an important role in many inflammatory diseases by binding to its receptor,Formyl Peptide Receptor 2(FPR2).However,whether CGA can affect Rv D1,and the role and mechanism of CGA and Rv D1 in chronic stress-induced liver inflammation remain unclear.To explore the mechanism of CGA in the treatment of chronic stress-induced liver inflammation,we established a rat model of chronic restraint stress-induced liver inflammation by administration of CGA and Rv D1 receptor inhibitor WRW4,to find new targets and new ideas for pharmacological action of CGA.Thirty male Wistar rats were selected and randomly assigned to the control group(CON group),chronic restraint stress group(CRS Group),chlorogenic acid group(CRS+CGA Group;100 mg/kg),and Rv D1 receptor inhibitor WRW4 group(CRS+CGA+WRW4 group;0.1 mg/kg),CRS+CGA+DMSO Group.Except for the CON group,the remaining four groups were under restraint stress from 6 hours per day to fasting and water deprivation for 21 days.After the model was established,the behavior was evaluated,the content of Corticosterone(CORT)was detected,the pathological damaged in the liver were observed,the indicators of liver function and the content of Rv D1 were detected,the expression levels of Rv D1 synthetase 5-LOX,15-LOX protein,receptor protein FPR2,and NF-κB pathway-related protein were detected.Results: compared with the CON group,the total distance of the CRS Group was significantly shortened,the average speed was significantly decreased,the times of entering Central District and standing were significantly decreased(P<0.05,P<0.01),and the serum CORT concentration was obviously elevated in the CRS group(P<0.01).ALT and AST were significantly added(P<0.05,P<0.01).The results of histopathology showed that the structure of liver cells was destroyed,the arrangement of liver platelets was disordered,and there were lymphocyte aggregation and infiltration of red blood cells,the expression of TNF-α,IL-1β,IL-6protein,and m RNA were all increased(P<0.05,P<0.01),which indicated that chronic stressinduced liver inflammation in rats The expression of 5-LOX and 15-LOX decreased significantly(P<0.01),the content of Rv D1 in serum and liver decreased(P<0.05,P<0.01),the transcription and protein expression of FPR2 had no difference,and the expression of IRAK1,TRAF6,pP65/P65,p-IκB/IκB increased(P<0.05,P<0.01).The results of immunofluorescence staining showed that the expression of P65 was increased in the nucleus.After administration of CGA,the rats’ adaptability to the strange environment was improved,the excitability and exploratory activity were restored to some extent,the concentration of CORT hormone was significantly decreased(P<0.01),the chronic stress was ameliorated,the pathological damage of liver was alleviated,the structure of hepatocytes was clear,the hepatic cords were arranged neatly,and the sinusoids were obvious,ALT and AST were all decreased to the healthy range;the level of Rv D1 was increased(P<0.01),the genetic transcription and protein expression of inflammatory factors were declined(P<0.05,P<0.01),and the protein expression of NF-κB pathway was decreased(P<0.05,P<0.01),liver inflammation improved.WRW4 inhibitor inhibited CGA-induced chronic stress relief,aggravated liver pathological injury,decreased R v D1 expression,and aggravated liver inflammation by over-activation of the NF-κB pathway.The results indicated that chronic restraint stress could activate the NF-κB signal pathway and induce liver injury.CGA treatment can promote the expression of R v D1 and alleviate liver injury by inhibiting the stimulation of the NF-κB signaling pathway and reducing the level of inflammation.