Su Jinsong, Yang Fujing, Kang Xuemei, Liu Jia, Tao Yiwen, Diao Qingchun, Meng Xianli, Liu Deming, Zhang Yi
School of Ethnic Medicine, and Research Institute of Integrated TCM and Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Chongqing Clinical Research Center for Dermatology, Chongqing Key Laboratory of Integrative Dermatology Research, Key Laboratory of External Therapies of Traditional Chinese Medicine in Eczema, Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
Front Pharmacol. 2022 Jul 7;13:932198. doi: 10.3389/fphar.2022.932198. eCollection 2022.
Three chalcone derivatives, abelmanihotols A-C , and nine known compounds were isolated from seeds, and their structures were determined using HRESIMS and NMR spectroscopic analysis. Compound exhibited the most potent inhibitory effect (IC = 4.79 ± 0.72 μM) against lipopolysaccharide (LPS)-induced NO release in THP-1 cells, and ignificantly inhibited interleukin 1β (IL-1β) secretion, which is stimulated by LPS plus nigericin (IC = 11.86 ± 1.20 μM), ATP or MSU, in THP-1 cells. A preliminary mechanism of action study indicated that compound 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 is not only a potent and efficacious NLRP3 inflammasome inhibitor but also a promising drug for the treatment of NLRP3-related diseases.
从种子中分离出三种查尔酮衍生物阿贝马尼霍醇A - C以及九种已知化合物，并通过高分辨电喷雾电离质谱（HRESIMS）和核磁共振波谱分析确定了它们的结构。化合物对脂多糖（LPS）诱导的THP - 1细胞中NO释放表现出最强的抑制作用（IC₅₀ = 4.79 ± 0.72 μM），并显著抑制LPS加尼日利亚菌素（IC₅₀ = 11.86 ± 1.20 μM）、ATP或微晶尿酸刺激THP - 1细胞分泌的白细胞介素1β（IL - 1β）。一项初步作用机制研究表明，该化合物通过抑制凋亡相关斑点样蛋白寡聚化来阻断核苷酸寡聚化结构域样受体蛋白3（NLRP3）炎性小体的形成，从而减弱半胱天冬酶 - 1的激活和IL - 1β的释放。这些结果表明，该化合物不仅是一种强效且有效的NLRP3炎性小体抑制剂，也是一种有前景的用于治疗NLRP3相关疾病的药物。
