Estudo das atividades anti-inflamatória e cicatrizante das folhas de Pereskia aculeata Miller (Cactaceae)

Abstract

The leaves of Pereskia aculeata Miller (Cactaceae) are used in traditional medicine, as wound healing and to treat inflammatory process. This study aimed to evaluate the in vivo topical anti-inflammatory and antipsoriatic activities of the hexane partition (PHEX) obtained from the crude methanol extract (EBM) of the leaves, and the in vivo topical wound healing activity of PHEX and EBM, in addition to the PHEX chemical characterization by gas chromatography coupled to mass spectrometry. The PHEX acute topical anti-inflammatory activity, the mouse ear edema model induced by the following different phlogistic agents was used: croton oil, arachidonic acid, ethylphenylpropiolate, capsaicin, phenol and histamine. The PHEX topical chronic anti-inflammatory activity was studied by the multiple application cróton oil-induced ear edema test in mice, followed by the histopathological analysis. PHEX mechanism of action was proposed based on its response after the challenge with different inflammatory stimuli, tissue cytokines levels and croton oil single application test after the pretreatment with mifepristone, an glucocorticoid antagonist. The PHEX oral anti-inflammatory action was also evaluated in vivo by the single and multiple croton oil ear edema test. PHEX antioxidant potential was evaluated in vitro by DPPH bioautography, β-carotene/linoleic acid and phosphomolybdenum assays, as the presence of antioxidant constituents may be helpful to treat inflammation. The PHEX antipsoriatic potential was evaluated by the mouse tail test. The PHEX and EBM wound healing activity was evaluated by the murine excisional wound model, laser Doppler perfusion image (LDPI) technique and histophatological analysis of the tissue on the last day of experiment. The PHEX topical toxicity was also studied by the irritation/corrosion and cutaneous atrophy tests. PHEX showed remarkable acute and chronic anti-inflammatory activity against all the phlogistic agents, except for arachidonic acid. Besides, antipsoriatic potential was observed. PHEX mechanism of action is related, at least in part, to a glucocorticoid effect. For this reason, a pharmaceutical formulation contained PHEX was developed, which topical acute and chronic anti-inflammatory activity was evaluated by the single and multiple croton oil-induced ear edema test. Due to the promising results, a patent of this product was deposited in National Institute of Intellectual Property (INPI). The PHEX acute oral anti-inflammatory effect was moderate, and a chronic activity was not observed. The antioxidant assays revealed that PHEX is endowed with antioxidant compounds, which may be contributing to its action. Besides, both PHEX and EBM accelerated the wound healing in mice, and PHEX also increased the blood flow and collagen deposition. The PHEX chemical characterization revealed the marked presence of sitosterol, stigmasterol, campesterol, taraxerol and taraxasterol, chemical compounds that may be the main responsible for the pharmacological activities reported in this study.