Interleukin-1 (IL-1) and
tumor necrosis factor-alpha (
TNF-alpha) are major proinflammatory
cytokines inducing the synthesis and release of many inflammatory mediators. They are involved in immune regulation,
autoimmune diseases, and
inflammation.
Acanthoic acid, (-)-pimara-9(11),15-dien-19-oic
acid, is a pimaradiene
diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum. When human monocytes/macrophages stimulated with
silica were treated with 0.1-10 microg/ml
acanthoic acid, the production of
IL-1 and
TNF-alpha was inhibited up to 90%, but the production of
interleukin-6 (IL-6) was not inhibited at all. At these concentrations, it had no cytotoxic effect on human monocytes/macrophages. It also suppressed the production of
TNF-alpha by alveolar macrophages and lymphocytes stimulated with
silica. In addition,
acanthoic acid inhibited the release of
superoxide anion and
hydrogen peroxide from human monocytes/macrophages and neutrophils. To know the antifibrotic effects of
acanthoic acid, its effects on fibroblast proliferation and
collagen synthesis were tested. The proliferation of NIH3T3 cells was inhibited almost completely by the addition of the culture supernatants of human monocytes/macrophages treated with
acanthoic acid, but not by the addition of
acanthoic acid only. In vitro and in vivo treatment with
acanthoic acid reduced
collagen production by rat lung fibroblasts and lung tissue. Furthermore,
acanthoic acid suppressed
granuloma formation and
fibrosis in the experimental
silicosis.
Acanthoic acid reduced serum GOT and GPT in the rats with
cirrhosis induced by CCl4, and it was effective in reducing hepatic
fibrosis and nodular formation. Taken together, these data indicate that
acanthoic acid has a potent anti-inflammatory and antifibrosis effect by reducing
IL-1 and
TNF-alpha production.