Soyasaponins reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts

作者：Junbin Chen, Hidayat Ullah, Zhongdaixi Zheng, Xiangfu Gu, Chuhong Su, Lingyu Xiao, Xinglong Wu, Fei Xiong, Qing Li, Longying Zha · 发表于：BMC Complementary Medicine and Therapies · 年份：2020 · DOI：10.1186/s12906-020-2864-2 · 被引用次数：33 · 研究领域：Immune Response and Inflammation、Phytoestrogen effects and research、Natural product bioactivities and synthesis

Abstract Background Previous studies indicate that soyasaponins may reduce inflammation via modulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling. However, its underlying mechanisms are still not fully understood. Methods Lipopolysaccharide (LPS)-challenged inflamed male ICR mice were intervened by intragastrical administration with 10 and 20 μmol/kg·BW of soyasaponin A 1 , A 2 or I for 8 weeks. The serum inflammatory markers were determined by commercial kits and the expression of molecules in TLR4/MyD88 signaling pathway in liver by real-time PCR and western blotting. The recruitments of TLR4 and MyD88 into lipid rafts of live tissue lysates were detected by sucrose gradient ultracentrifugation and western blotting. LPS-stimulated RAW264.7 macrophages were treated with 10, 20 and 40 μmol/L of soyasaponin A 1 , A 2 or I for 2 h. MyD88-overexpressed HEK293T cells were treated with 20 and 40 μmol/L of soyasaponins (A 1 , A 2 or I) or 20 μmol/L of ST2825 (a MyD88 inhibitor) for 6 h. The expression of molecules in TLR4/MyD88 signaling pathway were determined by western blotting. Data were analyzed by using one way analysis of variance or t-test by SPSS 20.0 statistical software. Results Soyasaponins A 1 , A 2 or I significantly reduced the levels of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and nitric oxide (NO) in serum ( p < 0.05), and decreased the mRNA levels of TNFα, IL-6, IL-1β, cyclooxygenase 2 (COX-2) and inducible nit...