title: 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.
authors.affiliation: Sansom Institute for Health Research, University of South Australia , Frome Road, Adelaide, 5000, South Australia.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Simpson
authors.forename: Xianling
authors.initials: X
authors.lastname: Luo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Costabile
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Caughey
authors.forename: Jiping
authors.initials: J
authors.lastname: Wang
authors.forename: David J
authors.initials: DJ
authors.lastname: Claudie
authors.forename: Ross A
authors.initials: RA
authors.lastname: McKinnon
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Semple
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001315:Australia; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D045785:Diterpenes, Clerodane / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D011565:Psoriasis / Q000188:drug therapy; D029631:Sapindaceae / Q000737:chemistry*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D045785:Diterpenes, Clerodane; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C587407:polyandric acid A; D009569:Nitric Oxide; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate