Soy isoflavones (daidzein & genistein) inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cutaneous inflammation via modulation of COX-2 and NF-κB in Swiss albino mice

Abstract

It is well established that aberrant production of inflammatory mediators has been associated with most the toxic manifestations and the genesis of different chronic diseases including cancer. The basic aim of the present study is to investigate the effects of soy isoflavones (SIF) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cutaneous inflammatory responses and to explore the underlying molecular mechanisms. We have studied the protective effects of SIF against TPA induced oxidative stress, pro-inflammatory cytokines level, activation of NF-κB, expression of COX-2 and ki-67 in mouse skin. Animals were divided into five groups I-V (n=6). Groups II, III and IV received topical application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day, for 2 days. Animals of the groups III and IV were pre-treated with SIF 1.0 μg (D1) and 2.0 μg (D2) topically 30 min prior to each TPA administration, while groups I and V were given acetone (0.2 ml) and SIF (D2), respectively. We have found that SIF pretreatment significantly inhibited TPA induced oxidative stress, proinflammatory cytokines production and activation of NF-κB. SIF also inhibited the expression of COX-2 and ki-67. Histological findings further supported the protective effects of SIF against TPA-induced cutaneous damage. Thus, our results suggest that inhibitory effect of SIF on TPA-induced cutaneous inflammation includes inhibition of proinflammatory cytokines, attenuation of oxidative stress, activation of NF-κB and expression of COX-2.