Anti-inflammatory effects of resveratrol analogues in cellular models of airway inflammation

Resveratrol has shown promising anti-inflammatory effects in airway disease models but poor pharmacokinetics and potency impede its therapeutic application. Recently, its methoxylated analogues have emerged as candidates with improved pharmacological properties. This study investigated the anti-inflammatory effects of these analogues, namely isorhapontigenin, pinostilbene and pterostilbene. A549 cells were stimulated with 1 ng/mL IL-1β and the effect on IL-6 and CXCL8 release measured using ELISA (n=4-6). Their effect on NF-κB activation was assessed using A549 cells stably transfected with NF-κB luciferase reporter gene (n=4). For IL-6 release, the IC₅₀ value of pinostilbene tended to be lower but only isorhapontigenin was significantly more potent than resveratrol. Isorhapontigenin and pterostilbene inhibited CXCL8 release with lower IC₅₀ values than resveratrol (Table 1). Resveratrol analogues, but not resveratrol, repressed NF- κB transcriptional activity (Table 1) and were more efficacious than dexamethasone which inhibited this response by ∼60% at 10 µM. This study identified analogues with superior anti-inflammatory effects than resveratrol and greater inhibition of NF-κB activity than dexamethasone. Their development as novel anti-inflammatory agents in airway inflammation is warranted.