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

Autor: 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
Rok vydání: 2018
Předmět:
Zdroj: Journal of Natural Medicines
ISSN: 1861-0293
1340-3443
DOI: 10.1007/s11418-018-1251-5
Popis: 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. Electronic supplementary material The online version of this article (10.1007/s11418-018-1251-5) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: