Effects of acanthoic acid on TNF-alpha gene expression and haptoglobin synthesis.

Tumour necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine inducing the synthesis and release of many inflammatory mediators. It is involved in immune regulation, autoimmune diseases, and inflammation. Our previous study demonstrated that acanthoic acid, (-)-pimara-9(11), 15-dien-19-oic acid, a pimaradiene diterpene isolated from Acanthopanax koreanum, inhibited TNF-alpha production. To extend our understanding of inhibitory effects of acanthoic acid on TNF-alpha production, its effects on TNF-alpha gene expression was tested. Based on the results from RT-PCR and promoter analysis of TNF-alpha, it was found that acanthoic acid suppressed TNF-alpha gene expression. But the same concentration of acanthoic acid had no effect on IL-6 gene expression. Haptoglobin is an acute phase protein which is induced by TNF-alpha. When liver cells were treated with acanthoic acid, haptoglobin synthesis was blocked by acanthoic acid. These data confirmed that acanthoic acid inhibited gene expression and biological function of TNF-alpha.