Biphenyls from Garcinia pedunculata and their anti-inflammatory activity through modulating NF-κB pathway

Twenty biphenyls including fifteen previously undescribed compounds (1-8 and 14-15) were isolated from the leaves of Garcinia pedunculata Roxb. The structures of these undescribed compounds were elucidated using high resolution electrospray ionization mass spectroscopy, ultraviolet spectrophotometry, nuclear magnetic resonance (NMR), and calculated ¹³C NMR with DP4+ analysis. The absolute configurations of the compounds were determined using electronic circular dichroism. All the isolated compounds were evaluated for their cytotoxicity and inhibitory effects on nitric oxide production with lipopolysaccharides induced RAW 264.7 cells. Notably, garpedunbiphenyl C (3), mangostanone Ⅲ (9), and garciesculenbiphenyl B (12) exhibited significant anti-inflammatory properties, with IC₅₀ values of 7.19 ± 0.38, 8.85 ± 0.62, and 13.64 ± 0.57 μM, respectively. Further assessment via enzyme-linked immunosorbent assay indicated that compounds 3, 9, and 12 dose-dependently inhibited the expression of proinflammatory cytokines IL-6 and TNF-α. At a concentration of 10 μM, compound 3 demonstrated a comparable inhibitory effect on IL-6 and TNF-α to that of dexamethason. Additionally, western blot analysis revealed that compound 3 significantly attenuated the expressions of iNOS, COX-2, and the NF-κB signaling pathway, thereby alleviating inflammatory responses.