Flavonoids and phenolic acids from Lablab Flos Alba and their anti-inflammatory activity via NLRP3 inflammasome

The flowers of Dolichos lablab L. (Lablab Flos Alba), a dual-purpose medicinal and dietary plant, exhibit significant nutritional and bioactive properties, though their phytochemical basis remains poorly characterized. To address this, a detailed phytochemical investigation was carried out on it, and twelve new compounds, namely flosdolilabflavonosides A₁-A₅, B (1-6), flosdolilabphenosides A, B, C₁, C₂, D₁, D₂ (7-12), along with thirty-two known flavonoids (13-44) were obtained. Twenty-six of the known isolates were reported for the first time in Lablab Flos Alba. And nine constituted new records for the Lablab genus. The effects of compounds 1-12 on the NLRP3 inflammasome were further explored by using LPS/Nigericin-stimulated bone marrow-derived macrophages (BMDMs) as in vitro model. Elisa assay revealed that compounds 6, 8, and 12 could significantly inhibit the release of interleukin-1β (IL-1β). Mechanistic studies via Western blotting demonstrated their dual regulatory effects: pretreatment with compounds 6, 8, and 12 downregulated NLRP3 and pro-IL-1β expression prior to LPS stimulation, while post-treatment with LPS/nigericin markedly reduced levels of cleaved IL-1β and cleaved caspase-1. These findings indicate that the anti-inflammatory activity of compounds 6, 8, and 12 arises from their interference with both the priming phase and the activation phase of NLRP3 inflammasome signaling.