Suppression of interleukin-1 and tumor necrosis factor-alpha production by acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, and it antifibrotic effects in vivo.
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.
Kang
H S
HS
Molecular Biomedicine Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Republic of Korea.
Kim
Y H
YH
Lee
C S
CS
Lee
J J
JJ
Choi
I
I
Pyun
K H
KH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D005355:Fibrosis / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010946:Plants, Medicinal; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012829:Silicosis / Q000188:drug therapy / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004224:Diterpenes; D007375:Interleukin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C099958:acanthoic acid