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Identification of β-carboline and canthinone alkaloids as anti-inflammatory agents but with different inhibitory profile on the expression of iNOS and COX-2 in lipopolysaccharide-activated RAW 264.7 macrophages

Liu, Pan, Li, Huixiang, Luan, Ruiling, Huang, Guiyan, Liu, Yanan, Wang, Mengdi, Chao, Qiuli, Wang, Liying, Li, Danna, Fan, Huaying, Chen, Daquan, Li, Linyu, Matsuzaki, Keiichi, Li, Wei, Koike, Kazuo, Zhao, Feng
Natural medicines 2019 v.73 no.1 pp. 124-130
Simaroubaceae, alkaloids, anti-inflammatory activity, anti-inflammatory agents, carboxylic acids, dose response, inducible nitric oxide synthase, lipopolysaccharides, macrophages, nitric oxide, prostaglandin synthase, prostaglandins, protein synthesis
A compound library, which consists of 75 natural β-carboline-type or canthinone-type alkaloids from Simaroubaceae plants and their chemical synthetic analogues, was screened for the anti-inflammatory activity by inhibition of the overproduction of inflammatory mediator nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Six compounds, namely, benzalharman (23), kumujian (27), 1-ethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (37), 1-acetophenone-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (42), cathin-6-one (46), and 9-methoxy-cathin-6-one (57), exhibited significant inhibitory activity on the overproduction of NO with good dose dependency. Further investigation demonstrated that all of the six compounds down-regulated the high expression of inducible nitric oxide synthase (iNOS) protein. Among them, two canthinone-type alkaloids (46 and 57) potently down-regulated cyclooxygenase-2 (COX-2) protein expression in a dose-dependent manner and also inhibited the overproduction of inflammatory mediator prostaglandin E₂ (PGE₂). However, the β-carboline-type alkaloids (23, 27, 37, and 42) exhibited no obvious inhibition on the overproduction of PGE₂ and the expression of COX-2 protein. The results suggested that β-carboline-type alkaloids and canthinone-type alkaloids may exert an anti-inflammatory effect through different mechanism.