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

Background: 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. Objective: 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. Materials and methods: 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. Result: 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. Conclusion: 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.