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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.