Multi-target anti-inflammatory and cytotoxic activities of flavonoids from Varthemia iphionoides Boiss. & C. I. Blanche.

Chronic inflammation plays a central role in the onset of many diseases, whereas long-term use of anti-inflammatory drugs is often associated with harmful side effects. This study examined the anti-inflammatory and cytotoxic effects of seven flavonoids isolated from Varthemia iphionoides Boiss. & C. I. Blanche: jaceidin (1), kumatakenin (2), 4'-hydroxy-3,5,6,7-tetramethoxyflavone (3), santin (4), quercetin-3,3'-dimethyl ether (5), viscosine (6), and isokaempferide (7). Compounds 1, 5 and 6 showed potent inhibition of ROS (IC50 in µM: 1.0, 1.7, and 11.4 in whole blood; 7.4, <0.3, and 9.9 in PMNs, respectively). All compounds, except compound 2, reduced NO• production (IC50: 9.1-26.9 µM). Compounds 3, 5 and 6 selectively inhibited COX-1. Most compounds exhibited low toxicity in BJ fibroblasts, whereas compound 5 showed potent and selective cytotoxicity against HeLa cancer cells. These findings highlight the multi-targeted anti-inflammatory potential of flavonoids, particularly compound 5, as a promising lead for research against inflammation-related diseases, including cancer.