Resveratrol analogue, HS-1793, inhibits inflammatory mediator release from macrophages by interfering with the TLR4 mediated NF-κB activation.

Resveratrol is known to have anti-inflammatory properties. However, high-dose resveratrol is required for optimal anti-inflammatory effects. HS-1793 is a derivative designed to be metabolically stable and more effective than resveratrol. We tested whether HS-1793 also has anti-inflammatory activity. HS-1793 effectively inhibited the mRNA and protein expression of lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in macrophages. Therefore, the production of nitric oxide (NO) and prostaglandin E (PGE) was significantly attenuated. In addition, HS-1793 completely suppressed the production of inflammatory cytokines enhanced by LPS treatment along with a decrease in Toll-like receptor 4 (TLR4) expression. At the same time, the expression of myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase 1 (IRAK1), and TNF receptor-associated factor 6 (TRAF6) signaling molecules and the nuclear translocation of nuclear factor kappa B (NF-κB)/p65 were also downregulated. We conclusively suggest that HS-1793 also exhibits anti-inflammatory properties by effectively inhibiting TLR4-mediated NF-κB activation.