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Polyandric acid A, a clerodane diterpenoid from the Australian medicinal plant Dodonaea polyandra, attenuates pro-inflammatory cytokine secretion in vitro and in vivo.

Abstract
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.
AuthorsBradley S Simpson, Xianling Luo, Maurizio Costabile, Gillian E Caughey, Jiping Wang, David J Claudie, Ross A McKinnon, Susan J Semple
JournalJournal of natural products (J Nat Prod) Vol. 77 Issue 1 Pg. 85-91 (Jan 24 2014) ISSN: 1520-6025 [Electronic] United States
PMID24400858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Diterpenes, Clerodane
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • polyandric acid A
  • Nitric Oxide
  • Peroxidase
  • Tetradecanoylphorbol Acetate
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (blood, chemistry, isolation & purification, pharmacology)
  • Australia
  • Cytokines (drug effects, metabolism)
  • Disease Models, Animal
  • Diterpenes, Clerodane (blood, chemistry, isolation & purification, pharmacology)
  • Ear (pathology)
  • Edema (chemically induced, 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, metabolism)
  • Plants, Medicinal (chemistry)
  • Psoriasis (drug therapy)
  • Sapindaceae (chemistry)
  • Skin (drug effects, pathology)
  • Tetradecanoylphorbol Acetate (pharmacology)
  • Tumor Necrosis Factor-alpha (analysis)

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