Anti-inflammatory Diterpenoids and Sesquiterpenoids from the Rhizomes of Shell Ginger (Alpinia zerumbet)

Shell ginger (Alpinia zerumbet) is a perennial species widely utilized as both an edible spice and a medicinal plant. Phytochemical investigation of its rhizomes yielded 33 terpenoids, of which 12 are previously undescribed compounds, comprising both diterpenes and sesquiterpenes. Notably, compound 1 represents a rare, highly oxygenated isospongiane-type diterpenoid with a novel skeleton. The anti-inflammatory potential of all isolates was assessed using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and BV2 microglial cells. Subsequent mechanism-oriented assays demonstrated that compounds 2 and 4 attenuated neuroinflammation in BV2 cells through an effect attributable to inhibition of nuclear factor kappa-B (NF-κB) nuclear translocation, reduction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and signal transducer and activator of transcription 3 (STAT3) protein expression, and downregulation of the mRNA levels of iNOS, interleukin-1β (IL-1β), COX-2, and tumor necrosis factor-α (TNF-α).