Polyandric Acid A, a Clerodane Diterpenoid from the Australian Medicinal Plant Dodonaea polyandra, Attenuates Pro-inflammatory Cytokine Secretion in Vitro and in Vivo

• Published in: Journal of natural products (Washington, D.C.) Vol. 77; no. 1; pp. 85 - 91
• Main Authors: Simpson, Bradley S, Luo, Xianling, Costabile, Maurizio, Caughey, Gillian E, Wang, Jiping, Claudie, David J, McKinnon, Ross A, Semple, Susan J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 24.01.2014
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Australia; Cytokines - drug effects; Cytokines - metabolism; Cytokines - secretion; Disease Models, Animal; Diterpenes, Clerodane - blood; Diterpenes, Clerodane - chemistry; Diterpenes, Clerodane - isolation & purification; Diterpenes, Clerodane - pharmacology; Dodonaea; Ear - pathology; Edema - chemically induced; Edema - drug therapy; Interleukin-1beta - antagonists & inhibitors; Interleukin-6 - analysis; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Mice; Mice, Inbred BALB C; Molecular Structure; Nitric Oxide - biosynthesis; Peroxidase - analysis; Peroxidase - metabolism; Plants, Medicinal - chemistry; Psoriasis - drug therapy; Sapindaceae - chemistry; Skin - drug effects; Skin - pathology; Tetradecanoylphorbol Acetate - pharmacology; Tumor Necrosis Factor-alpha - analysis; Australia
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np400704b

Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I’yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1β production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis.