14-Deoxygarcinol,a polyisoprenylated benzophenone from Garcinia cambogia,ameliorates inflammatory responses in adipose tissue via suppressing NLRP3 inflammasome

OBJECTIVE Interleukin(IL)-1β,one of the principal inflammatory cytokines mainly secreted by monocytes and macrophages,is produced by cleavage of the inactive pro-IL^(-1)βprecursor by caspase-1 via the NLRP3 inflammasome complex.The fruits of Garcinia cambogia(Clusiaceae)are widely developed as health products for anti-obese purpose.14-deoxygarcinol(DOG)is a polyisoprenylated benzophenone from the fruits of G.cambogia,which showed potent anti-inflammatory effect in our previous study.The objective of this study was to explore the anti-inflammatory mechanism of DOG and its roles in alleviating adipose tissue inflammation and insulin resistance.METHODS The anti-inflammatory effect of DOG was evaluated on LPS plus nigericin-induced THP-1 macrophages.The expression of NLRP3 inflammasome complex proteins was analyzed by Western blotting,immunofluorescence staining and co-immunoprecipitation.The pro-inflammatory cytokines levels were determined by ELISA kits.RESULTS DOG increased the expression of Sirtuin 2(SIRT2)deacetylase and enhanced its deacetylating activity to suppress the NLRP3 inflammasome activation and IL^(-1)βsecretion in THP-1 macrophages.Moreover,DOG attenuated macrophage conditioned medium-induced inflammatory responses in adipocytes and blocked THP-1 macrophages migration towards 3T3-L1 adipocytes.CONCLUSION DOG attenuated the inflammatory crosstalk between macrophages and adipocytes through SIRT2-mediated NLRP3 inflammasome inhibition,which might be used for the treatment of adipose tissue inflammation-related metabolic disorders.