Deoiled Sunflower Seeds Alleviate Abnormal 5-hydroxytryptamine Conversion In Chronic Stressed Mice And Its Mechanism

Reduced brain 5-hydroxytryptamine(5-HT)function is a vulnerable biological factor for the development of emotional stress and mood disorders.In recent years,the relationship between tryptophan(Trp)metabolism or a diet high in tryptophan and chronic stress-related disorders has received increasing attention.Previous studies have demonstrated that single doses of Trp or Trp rich whey protein enhanced the synthesis and release of 5-HT in the brain by increasing tryptophan intake,resulting in the prevention of chronic stress-induced brain5-HT depletion.Sunflower seeds are rich in Trp and may be a food ingredient for nutritional intervention to prevent and alleviate chronic stress.The purpose of this study was to investigate the effect of deoiled sunflower seeds on mice subjected to chronic unpredictable mild stress(CUMS)and its possible mechanism of action when it was used as the main protein source of dietary food,with the aim of providing a scientific basis for the development and utilization of sunflower seeds and related foods for the prevention of chronic stress.First,the effect of deoiled sunflower seeds on alleviating 5-HT depletion,oxidative stress and inflammatory response induced by chronic stress in mice was investigated.Male SPF6-week-old C57BL/6J mice were randomly divided into 6 groups(n=10 per group): normal group(CON,normal diet),model group(MOD,normal diet),deoiled sunflower seeds group(DSFS),deoiled and dechlorogenic sunflower seeds group(DDSFS),whey protein group(WPC,positive control),and fish collagen protein group(FCP,negative control).After 4weeks,all mice,except those in the CON group,were housed individually and exposed to CUMS for 3 weeks.The results showed that deoiled sunflower seeds significantly improved CUMS-induced reduction in sucrose preference,prolonged immobility in the tail suspension and forced swimming tests,reduced spontaneous activity and anxiety-like behavior in the open field and elevated plus maze tests,which is comparable to WPC.The Trp concentration and the ratio of Trp to large neutral amino acids in plasma were increased,and the levels of5-HT,dopamine,norepinephrine and brain-derived neurotrophic factor in hippocampus were increased,while the activity of indole 2,3-dioxygenase,which can cause 5-HT depletion,was decreased in deoiled sunflower seeds-fed group.These changes also accompanied the amelioration of inflammatory abnormalities and oxidative stress,and a decrease in plasma corticosterone.The effect of deoiled sunflower seeds on intestinal mucosal barrier and the composition of colonic flora in mice were further explored.The results showed that deoiled sunflower seeds significantly reduced plasma endotoxin and diamine oxidase levels,upregulated tight junction related protein and Mucin-2 m RNA expression levels in colon,suggesting improved intestinal mucosal barrier and intestinal permeability.Deoiled sunflower seeds caused significant changes in intestinal flora beta diversity,an increase in Butyrivibrio,Alistipes and Helicobacter,and a decrease in Alloprevotella in CUMS-induced mice,as well as significant increases in colon contents of propionic acid and valeric acid.The effect of DSFS and DDSFS on intestinal flora composition and short-chain fatty acid content were comparable to WPC.Finally,the effect of deoiled sunflower seeds on metabolites in hippocampus and colon content of mice were explored using a broadly targeted metabolome.The results showed that deoiled sunflower seeds significantly ameliorated CUMS-induced endogenous metabolite abnormalities in the hippocampus and colon content.Twenty-eight differential stress-related metabolites were screened in the hippocampus,mainly involving metabolic pathways such as glycerophospholipid metabolism;aminoacyl-t RNA biosynthesis;branched-chain amino acids biosynthesis,pyrimidine metabolism and purine metabolism.Eighteen markers were screened from colon content,mainly involving metabolic pathways such as tryptophan metabolism,aminoacyl-t RNA biosynthesis;branched-chain amino acids biosynthesis;aromatic amino acids biosynthesis;pyrimidine metabolism and purine metabolism.Deoiled sunflower seeds can restore abnormal metabolites to normal levels and significantly improve multiple metabolic pathways such as amino acid metabolism,nucleotide metabolism and lipid metabolism in stressed mice,thus improving their stress status.In summary,deoiled sunflower seeds effectively increased Trp bioavailability and alleviated CUMS-induced 5-HT depletion in the hippocampus,thereby preventing decreased pleasure,anxiety-like behavior,oxidative stress,and inflammatory responses.Meanwhile,deoiled sunflower seeds improved intestinal mucosal barrier function,intestinal permeability and colonic flora composition,amino acid metabolism,nucleotide metabolism,and lipid metabolism in stressed mice.