期刊
LIFE-BASEL
卷 12, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/life12122022
关键词
harmine; macrophages; TLR; inflammation; iNOS; TNF-alpha; NF-kappa B; JNK; AP-1; STAT1
资金
- Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through the High Value-added Food Technology Development Program - Ministry of Agriculture, Food and Rural Affairs (MAFRA)
- [116005-3]
This study reveals that harmine can effectively modulate the inflammatory response in macrophages by regulating the activity of NF-kappa B, JNK, and STAT1. It shows potential therapeutic significance in the treatment of infectious inflammation.
Harmine is a beta-carboline alkaloid present in various plants, including in the seeds of Peganum harmala L. This study aimed to investigate the anti-inflammatory activity and mechanism of harmine using macrophages stimulated with various toll-like receptor (TLR) agonists and a model of endotoxemia. The expression of inflammatory mediators induced by ligands of TLRs 2, 3, 4, and 9 were examined in thioglycollate-elicited peritoneal macrophages isolated from BALB/c and C57BL/6 mouse strains. Further, the activation of NF-kappa B, MAPK, AP-1, and STAT1 was explored using lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly(I:C)). Finally, the liver inflammatory response during endotoxemia was examined. Harmine inhibited inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-12, and other markers induced by various TLR agonists. The inhibition of NF-kappa B activity by harmine occurred via the modulation of p65 phosphorylation, independent of I kappa B alpha degradation. The inhibition of AP-1 activity by harmine was associated with the modulation of JNK. Harmine inhibited the LPS-induced serine and tyrosine phosphorylation of STAT1, but only affected serine phosphorylation by poly(I:C) treatment. In vivo, harmine inhibited iNOS and COX-2 expression during endotoxemia. Collectively, the results show that harmine can be effective against infectious inflammation through modulation of NF-kappa B, JNK, and STAT1.
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