Anti-inflammatory effect of lipophilic grape seed proanthocyanidin in RAW 264.7 cells and a zebrafish model

Grape seed proanthocyanidin (GSP), a major polyphenol in grape seed, has several remarkable physiological activities beneficial to human health. However, the hydrophilicity of GSP hampers its cellular absorption and thus limits the bio-efficiency in vivo. In order to enhance the lipophilicity of GSP for improved bio-efficiency, lipophilic grape seed proanthocyanidin (LGSP) was synthesized by enzymatic esterification of GSP. The anti-inflammatory activity of LGSP was evaluated in lipopolysaccharides-stimulated RAW 264.7 cells in vitro and a zebrafish tail-amputated model in vivo. LGSP exhibited strong inhibitory effects on the production of NO and pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in RAW 264.7 cells. Further mechanistic studies showed that LGSP achieved the aforementioned effects by inhibiting the activation of MAPKs and NF-κB signaling pathways. In the zebrafish model, LGSP effectively suppressed the aggregation of neutrophils. Our findings suggest that LGSP may be effective as a complementary agent for the prevention/treatment of inflammation-mediated diseases.