C-glycosylated and alkylated flavonoids with potent anti-inflammatory activity from the whole plants of Drymaria cordata.

Drymaria cordata is a traditional Chinese medicinal plant used for the treatment of hepatitis and chronic nephritis. Six previously undescribed flavonoid C-glycosides (1-3, 8, 9, 11), two unreported alkylated flavonoids (4, 5), and four known flavonoids (6, 7, 10, 12) were isolated from its 70 % ethanol extract. The structures were established by extensive analysis of NMR, HRMS, and X-ray single-crystal diffraction. All compounds exhibited inhibitory activity against nitric oxide production, with compound 8, which contains a rare sugar moiety (3,5-dihydroxy-6-methyl-γ-pyrone), showing the most pronounced effect. Further investigation revealed that 8 suppressed the expression of several key cytokines and inhibited the phosphorylation of p65. Molecular docking studies indicated that 8 targeted IKK, an upstream regulator of the NF-κB pathway, thereby blocking its activation.