Anti-Inflammatory and Immunoregulatory Activities In Vitro of Coumarins Isolated from the Twigs and Leaves of Wikstroemia indica (L.) C.A. Mey.

Six coumarins were isolated from two bioactive fractions of the 70% ethanol extract from the twigs and leaves of Wikstroemia indica (L.) C.A. Mey. (Thymelaeaceae), namely the ethyl acetate fraction (WIE) and the water fraction (WIW). These compounds were identified as umbelliferone (1), daphnoretin (2), daphnorin (3), adicardin (4), wikstronutin (5), and triumbelletin-7-O-β-D-glucoside (6). Compound 4 is reported for the first time in the genus Wikstroemia, whereas compound 5 is newly identified in this species. All six compounds were evaluated for their effects on Interleukin-1 beta (IL-1β) and IL-10 secretion in Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, among which compounds 1, 2, 5, and 6 showed stronger activity. These four coumarin derivatives further suppressed the production of Foxp3, Interferon-alpha (IFN-α), IFN-γ, and IL-17 in LPS- stimulated CD4+ T cells. The IC₅₀ values ranged from 18.84 ± 1.16 to 43.45 ± 5.34 μM for Foxp3, 8.96 ± 1.45 to 22.42 ± 4.12 μM for IFN-α, 9.28 ± 1.23 to 16.83 ± 2.15 μM for IFN-γ, and 12.62 ± 2.57 to 22.92 ± 4.41 μM for IL-17. Notably, compound 6 exhibited the strongest immunomodulatory effect. Overall, the findings suggest that coumarins from W. indica possess promising immunomodulatory and anti-inflammatory potential.