Sapelenins G–J, acyclic triterpenoids with strong anti-inflammatory activities from the bark of the Cameroonian medicinal plant Entandrophragma cylindricum

In this manuscript, we report the isolation and characterization of sapelenins G–J (1–4), from the Cameroonian medicinal plant, Entandrophragma cylindricum, along with their anti-inflammatory and cytotoxic activities. [Display omitted] ► Acyclic triterpenes,sapelenins G–J (1–4) isolated from Entandrophragma cylindricum. ► Eight known compounds isolated in parallel. ► Anti-inflammatory activities evaluated by IL-17 ELISA. ► Cytotoxicity towards PBMCs also evaluated. ► Potent anti-inflammatory compound discovered. Four acyclic triterpene derivatives named sapelenins G–J (1–4), along with eight known compounds, sapelenins A–D, ekeberin D2 (5), (+)-catechin and epicatechin, and anderolide G, were isolated from the stem bark of the Cameroonian medicinal plant, Entandrophragma cylindricum Sprague, on the basis of bioassay-guided fractionation. Their structures were determined by means of high-resolution mass spectrometry and NMR spectroscopic data, as well as by comparison with the literature values of their analogs. The absolute configurations of the compounds (1–4) were assigned by the modified Mosher’s method in conjunction with NOESY experiments and chemical modifications. The anti-inflammatory activities of the sapelenins were evaluated by assessing their ability to suppress or inhibit the secretion of cytokine interleukin-17 (IL-17) by human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). The cytotoxicity of these compounds on PMBCs was further assessed for correctly interpreting their anti-inflammatory responses. The tested compounds demonstrated moderate to significant anti-inflammatory activities by suppressing the secretion of IL-17 by PHA-stimulated human PBMCs. One of them, sapelenin G (1), showed high potency in suppressing the secretion of IL-17 by PBMCs comparable to reference cyclosporine A, without causing any cytotoxic effects (negligible), and deserves further considerations towards developing an effective anti-inflammatory drug.