Astragalin and rutin restore gut microbiota dysbiosis, alleviate obesity and insulin resistance in high-fat diet-fed C57BL/6J mice

In the present study we investigated the impact of the combination of astragalin and rutin(CAR)on restoring gut-microbial dysbiosis and obesity and obesity related disorders.Randomized male C57BL/6J mice were experimentally divided into 5 groups and fed either a normal diet or a high-fat diet(HFD)for 16 weeks.Compared to vehicle treated group(HFD group),CAR could substantially improve selected gut microbiota abundance(Akkermansia,Lactobacillus,Bifidobacteria,Roseburia,Prevotella),reversed the Firmicutes/Bacteroidetes proportions,and inhibited the growth of Escherichia coli,Salmonella,and Klebsiella in obese mice.In addition,CAR-treated mice showed significantly increased total short-chain fatty acid production,reduced body weight gain,organs’weights,serum lipid profile(except HDL)and insulin resistance.The mRNA expressions of CCAAT/enhancer binding protein-α(C/EBP-α),sterol regulatory element-binding protein-1c(SREBP-1c),peroxisome proliferator-activated receptor-γ(PPAR-γ),acetyl-CoA carboxylase(ACC),adipocyte protein 2(aP2),and fatty acid synthase(FAS)were downregulated(P<0.05)and the protein expression of PPAR-γwas downregulated while adenosine 5’monophosphate-activated protein kinase(AMPK)was phosphorylated in CAR-treated HFD-fed mice compared to the HFD control group.Interestingly,CAR-treated HFD-fed mice showed significantly improved tissue architecture in the liver and fatty tissues.In conclusion,the findings suggest that CAR/Moringa oleifera may be beneficial in the treatment of insulin resistance and obesity disorders.

Antioxidative,antimicrobial and anti-inflammatory activities and release of ultra-filtered antioxidative and antimicrobial peptides during fermentation of sheep milk:In-vitro,in-silico and molecular interaction studies

The antioxidative,antimicrobial,and anti-inflammatory properties of fermented sheep milk with L.fermentum (KGL4),as well as the generation of antioxidative and antimicrobial peptides,are evaluated in the study.Antioxidative and antibacterial activities in sheep milk fermented with KGL4 increased with incubation hours,along with varied antioxidative properties (ABTS assay:35.12%,hydroxyl free radical scavenging assay:29.12%,superoxide free radical scavenging activity:36.38%).Antimicrobial activity of fermented sheep milk against E.faecalis (19 mm),S.typhimurium (15.67 mm),B.cereus (14 mm),and E.coli (13 mm) was also observed.Furthermore,after 48 h,the KGL4 showed maximum proteolysis (10.40 mg/ml) at 2.5% rate of addition sheep milk.The antioxidative and antimicrobial activities of fermented sheep milk fractions (3 kDa and 10 kDa permeates and retentates) were also investigated.The highest ABTS activity (26.90%) was found in 10 kDa permeate,whereas the 3 kDa retentate had higher hydroxyl free radical scavenging activity (69.20%) and 3 kDa permeate showed maximum superoxide free radical scavenging activity (32.85%).The 10 kDa retentate had shown maximum antimicrobial activity against S.typhimurium (13.67 mm) and E.faecalis (17.00 mm).Proteins spotted on 2D gel electrophoresis of KGL4 were varied from 10 to 70 kDa.RP-LC/MS was used to identify 5 novel peptide sequences from 2-D gel spots.Searches in the BIOPEP database confirmed the antioxidative and antimicrobial effects of the novel fermented sheep milk peptides.Fermented sheep milk with KGL4 (SMKGL4) significantly reduced excessive TNF-α,IL-6,& IL-1β production in LPS-activated RAW 264.7 cells.