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Background: P1G10 is a cysteine proteolytic fraction from <i>Vasconcellea cundinamarcensis</i> latex, obtained by chromatographic separation on Sephadex-G10 and ultrafiltration. This fraction enhances healing in different models of skin lesions, and displays a protective/healing effect against gastric ulcers, where it was suggested an antioxidant role. Methods: We evaluated here the effect of topical treatment with P1G10, in mice lesions induced by UVB. Results: After single exposure to 2.4 J cm^&#8722;2 UVB, P1G10 reduced erythema, increased cellularity of hypodermis, enhanced MPO activity and IL1&#946;, and inhibited COX₂ levels. These results point to an anti-inflammatory effect by P1G10. This fraction displayed antioxidant activity by reversing the depletion of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and reducing the catalase activity increased by UVB. These changes may be related to a reduction in MDA observed in groups treated with P1G10. P1G10 also inhibited MMP-9, caspase-3 and pkat while increasing p53 levels.