Constituents from <i>Dolichos lablab</i> L. Flowers and Their Anti-Inflammatory Effects via Inhibition of IL-1β Release

Abstract

The occurrence of inflammation is closely related to the activation of the NLRP3 inflammasome. IL-1β produced during the activation of the NLRP3 inflammasome has strong pro-inflammatory activity and can also promote the release of inflammatory factors by other immune cells, exacerbating inflammatory damage to tissues. Utilizing IL-1β as the detection index to find small-molecule inhibitors targeting NLRP3 from natural products will benefit the search for drugs for inflammation-related diseases. During the exploration of anti-inflammatory active components derived from the flowers of Dolichos lablab L., an ingredient in traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, fourteen compounds (1–14), including seven previously unreported ones, named flosdolilabnitrogenousols A–D (1–4) and flosdolilabsaponins A–C (5–7), were found. Their structures were established through extensive NMR spectra determination, HR-ESI-MS analysis, ECD calculations, and chemical reactions. Flosdolilabsaponin A (5) stands out as an exceptionally rare tetracyclic lactone oleane-type saponin. Additionally, the inhibitory activity on IL-1β release of all compounds, without cytotoxicity, was evaluated using BMDMs stimulated with LPS/Nigericin. An Elisa assay revealed that compounds 1, 8, 9, and 11–14 exhibited significant inhibition of IL-1β release at a concentration of 30 μM. Structure–activity relationships were also discussed. This study indicates that D. lablab flowers possess anti-inflammatory activity, which might exert its effect by suppressing the activation of the NLRP3 inflammasome.

Keywords

• flowers of <i>Dolichos lablab</i> L.
• nitrogenous compounds
• terpenoid saponins
• IL-1β
• anti-inflammation