NO-donating Bergenin derivatives with enhanced anti-inflammatory activity

Ten new nitric oxide (NO)-donating Bergenin derivatives were designed, synthesized, and evaluated for their anti-inflammatory activity. Distinguished by its superior safety profile, a single furoxan moiety conjugated hybrid I₈ was selected for mechanistic studies. The results revealed that the anti-inflammatory effects of I₈ is probably related to the negative feedback inhibition of iNOS expression by promoting NO release, as well as the inhibition of the pro-inflammatory cytokines (TNF-α, IL-6) levels. These findings provide direct evidence supporting the hypothesis that BG-NO hybrids exert enhanced anti-inflammatory effects via NO signaling, identifying I₈ as a promising lead compound for further development.