Topical Anti-inflammatory Potential of Pumpkin (Cucurbita pepo L.) Seed Oil on Acute and Chronic Skin Inflammation in Mice

Background: Infl ammation is an adaptive response that is triggered by noxious stimuli and conditions, which involves interactions amongst many cell types and mediators, and underlies many pathological process. Unsaturated fatty acids (UFAs) can infl uence infl ammation through a variety of mechanisms, and have been indicated as alternative anti-infl ammatory agents to treat several infl ammatory skin disorders. Pumpkin seed oil (PSO) is rich in UFAs, but its topical antiinfl ammatory properties have not been investigated. Therefore, the aim of this paper was to evaluate the effects of PSO on acute and chronic cutaneous infl ammation experimental models. Materials, Methods & Results: PSO was purchased commercially and analyzed phytochemically. The topical anti-infl ammatory activity of PSO at different concentrations was evaluated on acute models (xylene- and 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema) and chronic model (multiple applications of oxazolone-induced dermatitis) in mice. Indomethacin and dexamethasone were used as reference drugs. The ear swelling was measured in both ear thickness (µm) and weight tissue (mg) at 1 and 4 h after xylene and TPA application, respectively. In the chronic model, the effectiveness of treatments was measured each 24 h post-challenge with oxazolone for 4 days. At the end of experiments, ear biopsies were assessed by histological analysis on hematoxylin-eosin- and toluidine blue-stained slides. Data were submitted to ANOVA followed Student Newman Keuls test (P < 0.05). PSO was characterized by a high content of unsaturated fatty acids (UFAs) (79.80%), including linoleic acid (ω-6, 55.83%) and oleic acid (ω-9, 23.47%). PSO caused a dose-dependent inhibition of xylene and TPA-induced ear edema in both skin thickness and weight when compared to respective positive controls (P < 0.05). This anti-infl ammatory effects was maximum when PSO was applied in nature (inhibition of 69.9 ± 2.8% and 78.1 ± 7.7% for infl ammation induced by xylene and TPA, respectively; P < 0.05), and was similar to, at least, one drug reference (P < 0.05). In addition, the topical treatment with PSO caused the inhibition of infl ammation-induced by oxazolone in 60.9 ± 9.8% when compared to control positive (P < 0.05), which was similar to dexamethasone (68.7 ± 8.1%, P < 0.05). In histological analysis, PSO reduced the infl ammatory parameters (edema, congestion, epidermal hyperplasia and cellular infi ltration) in infl ammation models studied. However, the number of mastocytes in cell infi ltration was reduced (17.6 ± 4.0) when compared to positive control (39.4 ± 5.8 cells) in chronic model (P < 0.05), but no differences were observed in acute models. Discussion: Topical anti-infl ammatory activity of plant-originated substances can be evaluated in several experimental models. In this study, we used as phlogistic agents: xylene, a promoter of neurogenic infl ammation; TPA, a phorbol ester that activate protein kinase C, leading to production of lipid-derived mediators; and oxazolone, an inductor of contact delayed-type hypersensitivity. Our results suggest that PSO alter infl ammatory response via modulation of cellular and molecular mediators involved in infl ammatory pathways activated by theses phlogistic agents. In addition, this oil was able to resolve a persistent infl ammatory lesion similar to dexamethasone, but we did not observe any cutaneous alterations caused by its topical use as related for corticosteroids. This is the fi rst report on topical anti-infl ammatory potential of PSO in acute and chronic skin infl ammation. This activity may be attributed the proper balance of ω-6 and ω-9 UFAs present in PSO, suggesting this oil as alternative therapy for the treatment of infl ammatory skin diseases. Further investigations are needed to support its application in clinical practice.