Soyasaponin A1 inhibits the lipid raft recruitment and dimerization of TLR4, MyD88, and TRIF by maintaining cholesterol homeostasis in palmitic acid-stimulated inflammatory Raw264.7 macrophage cell line

Gu, Xiangfu; Tang, Jiaqi; Zhao, Yue; Su, Chuhong; Xiao, Lingyu; Luo, Haiyan; Li, Hui; Xiong, Fei; Zheng, Zuoping; Chen, Junbin; Zha, Longying

doi:10.1016/j.jff.2021.104789

Cited by 4 publications

(2 citation statements)

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“…[30] SS-A 1 and SS-Bb also exert anti-inflammatory activities by inhibiting the lipid raft recruitment and dimerization of TLR4 and its downstream molecules MyD88 and TRIF. [31] Excessive lipids accumulation in liver is one of the core characteristics of NAFLD/NASH. Methionine and choline are key substrates for the synthesis of very low-density lipoprotein (VLDL).…”

Section: Discussionmentioning

confidence: 99%

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Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet‐Induced Non‐Alcoholic Steatohepatitis (NASH) Mice

Su,

Wang,

Luo

et al. 2024

Molecular Nutrition Food Res

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ScopeGut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS‐A1 and SS‐Bb) against NASH and explores the mechanisms by targeting GM.Methods and resultsMale C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS‐A1, SS‐Bb, or not for 16 weeks. Antibiotics‐treated pseudo germ‐free (PGF) mice are fed with MCD diet containing SS‐A1, SS‐Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC‐MS/MS. In NASH mice, SS‐A1 and SS‐Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF‐α, IL‐6, α‐SMA, triglycerides, and cholesterol in liver. SS‐A1 and SS‐Bb decrease Firmicutes, Erysipelotrichaceae, unidentified‐Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS‐A1 and SS‐Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO‐1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS‐A1 and SS‐Bb against NASH.ConclusionGM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet‐induced NASH mice.

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Section: Discussionmentioning

confidence: 99%

“…[ 30 ] SS‐A 1 and SS‐Bb also exert anti‐inflammatory activities by inhibiting the lipid raft recruitment and dimerization of TLR4 and its downstream molecules MyD88 and TRIF. [ 31 ]…”

Section: Discussionmentioning

confidence: 99%