AUTHOR=Su Jinsong , Yang Fujing , Kang Xuemei , Liu Jia , Tao Yiwen , Diao Qingchun , Meng Xianli , Liu Deming , Zhang Yi 

TITLE=Chalcone Derivatives From Abelmoschus manihot Seeds Restrain NLRP3 Inflammasome Assembly by Inhibiting ASC Oligomerization

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.932198

DOI=10.3389/fphar.2022.932198

ISSN=1663-9812

ABSTRACT=<p>Three chalcone derivatives, abelmanihotols A−C <bold>(1–3)</bold>, and nine known compounds were isolated from <italic>A. manihot</italic> seeds, and their structures were determined using HRESIMS and NMR spectroscopic analysis. Compound <bold>1</bold> exhibited the most potent inhibitory effect (IC<sub>50</sub> = 4.79 ± 0.72 μM) against lipopolysaccharide (LPS)-induced NO release in THP-1 cells, and <bold>s</bold>ignificantly inhibited interleukin 1β (IL-1β) secretion, which is stimulated by LPS plus nigericin (IC<sub>50</sub> = 11.86 ± 1.20 μM), ATP or MSU, in THP-1 cells. A preliminary mechanism of action study indicated that compound <bold>1</bold> 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 <bold>1</bold> is not only a potent and efficacious NLRP3 inflammasome inhibitor but also a promising drug for the treatment of NLRP3-related diseases.</p>