Elicited soybean extract attenuates proinflammatory cytokines expression by modulating TLR3/TLR4 activation in high−fat, high−fructose diet mice

Abstract

The high−fat, high−fructose diet (HFFD) provokes overnutrition and inflammation directly, mainly through Toll−like receptors (TLRs). Soybean (Glycine max L.) contains isoflavone that can be transformed into glyceollin by microbial and physical stimuli. Glyceollin possesses many beneficial effects on health. This study evaluates the beneficial effect of soybean extract elicited by Saccharomyces cerevisiae and light (ESE) on dendritic cells (DCs) profile and naïve T cells in HFFD mice. Female Balb/C mice were fed with HFFD for 24 weeks then orally administered with simvastatin 2.8 mg/kg BW or ESE 78, 104, and 130 mg/kg BW at the last four weeks. The expression of splenic CD11c+TLR3+, CD11c+TLR4+, NFκB+, CD11c+IL-17+, CD11c+TNF−α+, CD4+CD62L+, and CD8+CD62L+ subsets was measured by flow cytometry. The molecular docking has been measured using Pyrx 0.8, displayed in PyMol and Biovia Discovery Studio. HFFD significantly increased CD11c+TLR3+, CD11c+TLR4+, NFκB+, CD11c+IL-17+, CD11c+TNF−α+ expression and decreased CD4+CD62L+ and CD8+CD62L+ (p < 0.05) compared to normal diet (ND) groups. ESE reduced CD11c+TLR3+, CD11c+TLR4+, thereby decreasing NFκB+, as well as decreased the CD11c+IL−17+, CD11c+TNF−α+, and restores CD4+CD62L+ and CD8+CD62L+ subsets in HFFD mice. Glyceollin II exhibited the best binding affinity with an average energy of −7.3 kcal/mol to TLR3 and −7.9 kcal/mol to TLR4. The bioactive compound in ESE act synergistically to modulate TLR3/TLR4 activation, reduced NFκB, IL−17, and TNF−α, and restores naïve T cells expression in HFFD mice. ESE was a favorable candidate to mitigate chronic inflammation.