title: Topical isoflavonoids reduce experimental cutaneous inflammation in mice.
abstract: The antioxidant and anti-proliferative biological effects of isoflavonoids are relevant properties to counteract the characteristics of many cutaneous diseases. This study uses ultraviolet (UV)B irradiation to induce inflammation in the mouse skin, as a model for some symptoms of cutaneous inflammatory and hyperproliferative diseases such as psoriasis in humans, with the objective of testing two topically applied isoflavonoid compounds for therapeutic properties. UVB exposure resulted in the overexpression of the cytokines, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the adhesion molecule P-cadherin. Infiltration into the dermal compartment of mast cell populations was also induced. These factors are also overexpressed in psoriatic skin. The effect of topical applications of two isoflavonoids, equol and a synthetic analogue NV-38, was tested. Both isoflavonoids dose dependently inhibited the UVB induction of cutaneous TNF-α mRNA and protein, a cytokine critical for the initiation of psoriatic inflammation. Expression of IL-6 mRNA and protein was also decreased, and the number of infiltrating mast cells into the dermis was reduced by both isoflavonoids. Furthermore, the upregulated mRNA and protein levels of P-cadherin, a marker characteristic of cutaneous hyperproliferation, were also normalized by both isoflavonoids. These results suggest that this class of compounds has the potential for useful, innocuous anti-inflammatory therapy from topical application in human cutaneous diseases.
authors.affiliation: Faculty of Veterinary Science, Photobiology Group, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Bandara
authors.forename: Sondur Jayappa
authors.initials: SJ
authors.lastname: Arun
authors.forename: Munif
authors.initials: M
authors.lastname: Allanson
authors.forename: Sitarina
authors.initials: S
authors.lastname: Widyarini
authors.forename: Zacary
authors.initials: Z
authors.lastname: Chai
authors.forename: Vivienne Elizabeth
authors.initials: VE
authors.lastname: Reeve
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000528:radiation effects*; D003872:Dermatitis / Q000188:drug therapy*; D060754:Equol; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008407:Mast Cells; D051379:Mice; D008812:Mice, Hairless; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011565:Psoriasis / Q000188:drug therapy; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015820:Cadherins; D060754:Equol; D015850:Interleukin-6; D007529:Isoflavones; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C007610:4',7-dihydroxy-3,4-dihydroisoflavone