Multi-omics Of The Effect Of Apis Cerana Cerana Honey On Oxidative Stress-related Inflammatory Response

Under the background of healthy China strategy,researches on the exploration of natural food with nutrition and healthy function have become the hotspot in Food Science.Foods rich in antioxidants are contribute to oxidative stress-related inflammatory response.Honey has been not only favoured by consumers due to its unique flavor,but also possessed a wide use of pharmacological activities and biological functions as a natural dietary antioxidant.Among them,honey of Apis cerana cerana(A.cerana honey)has been used as a unique Chinese honey and folk medicine to treat constipation and alcohol-induced liver damage for thousands of years.The key to reveal the relationship of honey-human health is to define the effect of A.cerana honey on oxidative stress-related inflammatory response.Herein,based on the analysis of chemical composition,antioxidant activity in vitro and serum metabolic phenotype,the present study focus on the intervention effect and mechanism of honey on studied the improvment effect and underlying molecular mechanisms of honey on oxidative stress-related inflammatory response(alcohol-induced liver damage,ulcerative colitis and metabolic syndrome).This study establishes a theoretical foundation for development of bee products with antioxidant function,and provides new clues for application of multiomics in the field of Food Bioactivity.The main investigations and results are as follows:1.Based on the determination and characterization of the physicochemical properties,nutritional composition and phenolic compounds of A.cerana honey,its antioxidant activity in vitro was evaluated by chemical model and cell model.The results showed that the total phenolic content of A.cerana honey ranged from 345.1 mg/kg to 502.1 mg/kg,and the ascorbic acid content ranged from 153.8 mg/kg to 385.4 mg/kg.Caffeic acid and rutin were the dominant phenolic compounds with an average content of 30.4 mg/kg and 11.9 mg/kg respectively.In addition,A.cerana honey had strong DPPH radical scavenging activity(87.5-136.2 mg/m L),ferric ion reducing antioxidant power(176.5-317.4 mg/kg),ferrous ion-chelating activities(22.8-35.5 mg Na₂EDTA/kg)and protective effect against H₂O₂induced DNA oxidative damage.2.The effects of A.cerana honey on serum antioxidant capacity and metabolic phenotype were studied by metabolomics.The results showed that 25 kinds of biomarkers,including phenolic compounds,fatty acids and amino acids,were related to the enhancement of serum antioxidant capacity.These biomarkers mainly involved in COX-and LOX-related arachidonic acid metabolic pathway,reactive nitrogen production-related arginine metabolic pathway,and NF?B signaling pathway.3.The hepatoprotective effect of A.cerana honey on alcohol-induced liver damage in mice was studied.The results showed that 12-week-pretreatment with A.cerana honey significantly inhibited serum lipoprotein oxidation,increased serum oxygen free radical absorption capacity(p<0.05),inhibited the increase of serum ALT and AST,decreased liver MDA content,increased SOD and GSH-Px activities,and inhibited the level of TGF-?1 in serum and liver,which confirmed that A.cerana honey prevents acute alcohol-induced liver damage attributed to its antioxidant properties and intervention of oxidative stress.4.The underlying molecular mechanisms of A.cerana honey on DSS-induced ulcerative colitis were studied by gut microbiome.The results showed that the A.cerana honey and its phenolic compounds significantly increased the levels of SOD and GSH-Px,decreased the NO,MPO,TNF-?,TGF-?1 and IL-6,down-regulated the gene expression of IL-1?,IL-6,TNF-?and IFN-?,and up-regulated the gene expression of I?B-?.In addition,A.cerana honey and sulfasalazine showed similar gut microbiota structure.At the genus level,A.cerana honey significantly reduced the population of Bacteroides,Corynebacterium,and Proteus species.The correlation analysis indicates that colonic gene expression regulated by honey polyphenols is relative to the key species of gut microbiota.5.The effects of A.cerana honey on normal or metabolic syndrome mice were studied.The results showed that A.cerana honey could reduce the risk of metabolic syndrome in normal mice by inhibition of TC and LDL-C,regulation of the gut microbiota composition,and improve the oxidative stress-related inflammatory response to metabolic syndrome by improving liver lipid synthesis,oxidative stress homeostasis and inflammatory response,and restructuring gut microbiota and short chain fatty acid metabolites.