Chalcone Derivatives From Abelmoschus manihot Seeds Restrain NLRP3 Inflammasome Assembly by Inhibiting ASC Oligomerization
Jinsong Su, Fujing Yang, Xuemei Kang, Jia Liu, Yiwen Tao, Qingchun Diao, Xianli Meng, Deming Liu, Yi Zhang
Abstract
Three chalcone derivatives, abelmanihotols A−C (1–3) , and nine known compounds were isolated from A. manihot seeds, and their structures were determined using HRESIMS and NMR spectroscopic analysis. Compound 1 exhibited the most potent inhibitory effect (IC 50 = 4.79 ± 0.72 μM) against lipopolysaccharide (LPS)-induced NO release in THP-1 cells, and s ignificantly inhibited interleukin 1β (IL-1β) secretion, which is stimulated by LPS plus nigericin (IC 50 = 11.86 ± 1.20 μM), ATP or MSU, in THP-1 cells. A preliminary mechanism of action study indicated that compound 1 blocked the formation of nucleotide oligomerization domain-like receptor protein-3 (NLRP3) inflammasome formation by suppressing apoptosis-associated speck-like protein oligomerization, thereby attenuating caspase-1 activation and IL-1β release. These results reveal that compound 1 is not only a potent and efficacious NLRP3 inflammasome inhibitor but also a promising drug for the treatment of NLRP3-related diseases.