<i>In Vitro</i> and <i>in Vivo</i> Anti-Inflammatory Effect of a Biotechnologically Modified Borage Seed Extract: Evidence for Lipid Pro-Resolving Mediators’ Implication in the Enhancement of Psoriatic and Atopic Dermatitis Lesions

Abstract

Aim: Resolvins, maresins and lipoxins are lipid mediators issued from essential polyunsaturated fatty acids which are the first anti-inflammatory and pro-resolving signals identified during the resolution phase of inflammation. As borage oil and/or borage seed extracts have shown beneficial action in treatment of atopic dermatitis or eczema in human and canine, we have modified a borage oil component by using biotechnology in order to get a compound structurally related to a polyunsaturated fatty acid, and we have studied its ability to reduce inflammation mediators production through the generation of resolvins, maresins and/or lipoxins. Additionally, we have demonstrated the potent anti-inflammatory effect of this new compound which consists in borage seed oil aminopropanediol amides, through an in vivo study concerning subjects suffering from psoriasis or atopic dermatitis. Study Design/Methods: For the in vitro study, inflammation was induced in co-cultures of human dendritic cells and normal keratinocytes by the addition of PMA and the calcium ionophore A23187. Ability of our borage seed oil aminopropanediol amides to increase resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis was then measured. Pro-inflammatory cytokines (IL-1 β , IL-6, IL-8) and PGE2 productions were also quantified. For the in vivo study, 36 subjects suffering from psoriasis or atopic dermatitis have used twice a day during 30 days, a formulation containing borage seed oil aminopropanediol amides. Before the beginning of the study and after 30 days’ treatment, the severity of psoriasis and of atopic dermatitis was evaluated by using the PGA and the SCORAD scoring scales, respectively. Results: Borage seed oil aminopropanediol amides were able to significantly increase the resolvin D2, maresin 1 and lipoxins A4 and B4 synthesis. Concomitantly, they were also able to significantly inhibit the production of IL-1 β , IL-6, IL-8 and PGE2 induced by the PMA and the calcium ionophore A23187 in the in vitro co-culture model used. Introduced in formulation, borage seed oil aminopropanediol amides significantly reduced the clinical manifestations of psoriasis and atopic dermatitis. Conclusion: Our in vitro and in vivo study clearly showed the anti-inflammatory activity of borage seed oil aminopropanediol amides and emphasized the putative role of pro-resolving lipid mediators in the treatment of atopic dermatitis, psoriasis or other inflammation-induced skin diseases.