Effects of artesunate and dihydroartemisinin on LPS-activated macrophages

Abstract

Chronic inflammation is a complicated process mediated by the actions of many types of immune cells, notably, macrophages. Thus, there is a great deal of interest in launching new strategies to inhibit functions of activated macrophages associated with chronic inflammation. Artesunate (AS) and dihydorartemisinin (DHA), the artemisinin derivatives, have been shown to have pharmacological actions beyond anti-malarial effects. This study aimed to investigate and compare the effects of AS and DHA on lipopolysaccharide (LPS) activated macrophage J774A.1 cells. The results showed that AS and DHA markedly inhibited nitric oxide (NO) production in a concentration dependent manner with IC50 at 28.3 ± 3.5 µM for AS and at 13.12 ± 2.3 µM for DHA. The activities of AS and DHA on NO production were consistent with their inhibitory effects on mRNA expression of iNOS. AS and DHA at 10-50 µM significantly down-regulated mRNA expressions of pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) chemokines (MIP-1α and MCP-1), COX2, mPGES1, and decreased PGE2 production. By comparing between their IC50 values, AS and DHA had similar inhibitory effects on mRNA expression of IL-1, MIP-1α, iNOS, COX2, mPGES1, and on PGE2 production. DHA was more potent than AS on inhibiting NO production and on down-regulating mRNA expression of TNF-α and MCP-1. In contrast, AS showed higher inhibitory effect on IL-6 expression than DHA. Both AS and DHA increased mRNA expression of anti-inflammatory cytokine, IL-10 in LPS-activated macrophages. The results in this study demonstrated potent anti-inflammatory activities of AS and DHA. These results supported the potential use of artemisinin derivatives as anti-inflammatory agents in the future.