Multi-target anti-inflammatory and cytotoxic activities of flavonoids from <i>Varthemia iphionoides</i> Boiss. &amp; 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 <i>Varthemia iphionoides</i> Boiss. & C. I. Blanche: jaceidin (<b>1</b>), kumatakenin (<b>2</b>), 4'-hydroxy-3,5,6,7-tetramethoxyflavone (<b>3</b>), santin (<b>4</b>), quercetin-3,3'-dimethyl ether (<b>5</b>), viscosine (<b>6</b>), and isokaempferide (<b>7</b>). Compounds <b>1</b>, <b>5</b> and <b>6</b> 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 <b>2</b>, reduced NO• production (IC₅₀: 9.1-26.9 µM). Compounds <b>3</b>, <b>5</b> and <b>6</b> selectively inhibited COX-1. Most compounds exhibited low toxicity in BJ fibroblasts, whereas compound <b>5</b> showed potent and selective cytotoxicity against HeLa cancer cells. These findings highlight the multi-targeted anti-inflammatory potential of flavonoids, particularly compound <b>5</b>, as a promising lead for research against inflammation-related diseases, including cancer.