Research On The Synergistic Anti-inflammatory Effect And Dosage Optimization Of Chlorogenic Acid And Quercetin

Chlorogenic acid and quercetin are important active ingredient of Auricularia polyphenols,which have shown superior anti-inflammatory activities in in vivo and in vitro studies.Dietary intake of polyphenols will undergo complex metabolism in the body,and eventually reach the systemic circulation or specific tissues in the form of their metabolites to exert positive effects.In addition,dietary polyphenols are often not a single component,and there may be antagonistic,synergistic or additive effects among phenolic compounds,making it difficult to attribute the biological effects of dietary polyphenols to a single compound.Therefore,research on the metabolism and interaction of phenolic compounds in vivo is of great significance for the development of effective dietary therapy or dietary recommendations.In this study,we used intraperitoneal injection of lipopolysaccharide to induce a rat model of acute lung injury.By comparing the protective effects of chlorogenic acid,quercetin and chlorogenic acid-quercetin compound on acute lung injury,we explored the synergistic effect on anti-inflammatory between chlorogenic acid and quercetin.And their influence on the intestinal microflora of acute lung injury models was also clarified.The response surface method was used to optimize the dosage of chlorogenic acid-quercetin,and the differences in the composition of metabolites in different dosage treatment groups were compared.The concrete results can be summarized as follows:1)Chlorogenic acid,quercetin and chlorogenic acid-quercetin compound could effectively reduce the expression levels of TNF-?,IL-1? and IL-6 in serum and alveolar bronchoalveolar lavage fluid of ALI rats(P < 0.05),and effectively ameliorate the pathological changes of lung tissue and decrease the ratio of wet/dry weight of lung tissue(P < 0.05).Moreover,the protective effect of chlorogenic acid + quercetin compound was better than that of single ingredient at the same dose,indicating that there is a synergistic effect on anti-inflammatory between chlorogenic acid and quercetin.2)LPS-induced rats ALI model was treated with quercetin,chlorogenic acid and chlorogenic acid-quercetin compound,and there were significant differences in the composition of intestinal microflora between different treatment groups.After treatment with quercetin,chlorogenic acid and chlorogenic acid-quercetin,the abundance of pro-inflammatory bacteria such as Corynebacterium and Streptococcus decreased.The abundance of beneficial bacteria Bifidobacterium increased significantly in chlorogenic acid treatment group.In quercetin treatment group,the abundance of beneficial bacteria such as,Butyricimonas,Oscillospira and Bacteroides increased significantly,while the abundance of pathogenic bacteria Clostridium and Turicibacter decreased.And the abundance of Lactobacillus in chlorogenic acid + quercetin treatment group was significantly increased.These results may suggest that the protective effects of quercetin and chlorogenic acid on acute lung injury may be related to their regulation of inflammatory-related intestinal microbes.3)Taking the concentration of TNF-? in serum of rats as the evaluation index,the dosage of chlorogenic acid-quercetin was optimized by response surface analysis.The results showed that the optimal dosage was chlorogenic acid 27.868 mg/kg,quercetin 45.932mg/kg,which is close to the central point' dose(chlorogenic acid 30mg/kg,quercetin 45 mg/kg).4)13 metabolites of chlorogenic acid and quercetin were identified by UPLC-MS/MS.Compared with other groups,the central point(CP)dose group had higher concentrations of dihydroxylated phenolic acid(2,4-dihydroxybenzoic acid,3,4-dihydroxyphenylacetic acid)and p-coumaric acid in serum,which may be related to the stronger anti-inflammatory activities of CP dose group.