Proteins and lunasin from Glycine soja inhibited inflammation by activating the Hippo pathway through phosphorylation of YAP1 kinase

Abstract

The Hippo pathway has attracted scientific interest as a target for anti-inflammation and anti-cancer therapy. Our objective was to elucidate and compare the potential anti-inflammatory mechanism of digested whole flour (DWF), total protein extract (TPE), lunasin-free total protein extract (LFP), and enriched lunasin protein extract (ELPE) from wild-type soybean (Glycine soja) on the Hippo pathway, using a human monocytic cell (THP-1) as a model. ELPE (56% to 73% purity) showed increased lunasin concentrations (52 – 87 mg/g of defatted flour, DF) compared to TPE (16 – 33 mg/g, DF). TPE significantly decreased IL-6, MCP-1, and TNF-α production (96%, 76%, and 52%). G. soja inhibited IL-6 production (74% – 98%) more effectively compared to MCP-1 (6% – 99%). ELPE and TPE significantly (p ≤ 0.05) decreased the expression of dephosphorylated YAP1 and increased phosphorylated YAP1 (p ≤ 0.05). ELPE significantly increased (p ≤ 0.05) cytoplasmic YAP1 retention. G. soja proteins and peptides inhibited inflammation by decreasing pro-inflammatory cytokines IL-6, IL-1β, and MCP-1, phosphorylating YAP1 and LATS1/2, and increasing YAP1 cytoplasmic retention, thus activating the Hippo pathway. The results suggest that soybean proteins and peptides inhibited inflammation through the Hippo pathway, offering novel developments of functional food ingredients or supplements for a healthier diet.