Anti-inflammatory effects of TNF-α and ASK1 inhibitory compounds isolated from Schkuhria pinnata used for the treatment of dermatitis

Ethno-pharmacological relevance: The Andean Schkuhria pinnata species commonly known as 'Canchalagua' is used as an infusion in Andean countries to treat various anti-inflammatory and skin-related pathologies.Aim of the study: This study determined the anti-inflammatory activity of the aqueous extract from Schkuhria pinnata, identified compounds with high biological activity and performed a structure-activity relationship analysis to determine their binding mechanism.Materials and methods: A bio-guided isolation of the active compounds of Schkuhria pinnata was carried out by selecting the most active sub-extracts and fractions to test their anti-inflammatory activity against the ASK1 and TNF-alpha cytokines.Results: Three compounds were obtained, and their structures were elucidated by nuclear magnetic resonance. The compounds were (3R,4R)-4-(3,4-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl) dihydrofuran-2(3H)-one (1), N-[2,3-dihydro-1,3-dimethyl-6-[(2R)-2-methyl-1-piperazinyl]-2-oxo-1H-benzimidazol-5-yl]-2-methox-ybenzamide (2), and N-hydroxy-1-cyclopentene-1-carboxamide (3). Regarding their anti-inflammatory activity, the three compounds inhibited the TNF-alpha and ASK1 cytokines, however, compound 2 was the most active, with an IC50 of 19.08 and 8.94 nM, respectively.Conclusion: The anti-inflammatory activity of the aqueous extract of Schkuhria pinnata was evaluated, followed by the isolation of three compounds and the study of their pharmacological activity. The three compounds have been shown as promising treatment against dermatitis, confirming at the same time their traditional use.