Flavonoids of Tripodanthus acutifolius inhibit TNF-α production in LPS-activated THP-1 and B16-F10 cells.

Ethnopharmacological Relevance: T. acutifolius is an endemic species from South America which has been used in traditional medicine since ancient times due to its biological properties, including its anti-inflammatory effects.

Aim Of The Study: The aim of the article is to investigate the inhibitory activity of T. acutifolius over TNF-α production in THP-1 and B16-F10 cells. To achieve this, phytochemical analysis has been used to determine the compounds present in the species with anti-inflammatory effects.

Materials And Methods: Leaves and stems of T. acutifolius were extracted with n-heptane, dichloromethane, methanol and water. The resulting extracts were analysed in THP-1 and B16-F10 cells by measuring their inhibitory capacity over the production of TNF-α stimulated with LPS.

Results: The guided-bioassay led to the isolation of 6,2',4'-trimethoxyflavone (1), 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone (2), (E)-2',4'-dihydroxy-6'-methoxy-chalcone (3) and 5,4'-dihydroxy-6,7,8-trimethoxyflavone (4) from the dichloromethanic extract. Compounds showed an inhibitory activity of TNF-⍺ production in THP-1 cells, with IC of 2.38 ± 0.02 μM, 12.36 ± 0.17 μM, 1.12 ± 0.01 μM and 8.09 ± 0.04 μM, respectively. In addition, the compounds showed an inhibitory activity of TNF-⍺ production in B16-F10 cells with IC of 1.32 ± 0.03 μM, 5.63 ± 0.09 μM, 0.60 ± 0.02 μM and 3.77 ± 0.15 μM, respectively.

Conclusions: We identified 3 flavones (6,2',4'-trimethoxyflavone, 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone, 5,4'-dihydroxy-6,7,8-trimethoxyflavone) and a chalcone ((E)-2',4'-dihydroxy-6'-methoxy-chalcone) present in the leaves and stems of T. acutifolius. These compounds are an alternative for the treatment of immune-mediated inflammatory disorders, acting as negative modulators over the TNF-α production.