Efeito cicatrizante da fração metanólica das folhas de Sideroxylon obtusifolium: Estudo In vitro e em queimaduras superficiais em camundongos

Abstract

Burns correspond to 38% of the main diseases treated in the Unified Health System (SUS) in Brazil. Despite the new therapeutic strategies, the costs of treating burns are still quite high. The use of plants with therapeutic potential is widely used popularly, due to its low cost, easy access and great Brazilian biodiversity.Sideroxylon obtusifolium (quixaba) presented an anti-inflammatory and healing potential of the metanolic fraction of leaves (DFSO-M), previously described by the research group, which can be attributed to a major component (NMP) derived from L-proline, an amino acid precursor of the collagen synthesis present in this fraction. Thus, the objective of this work was to investigate the effect of DFSO-M on murine fibroblast (L929), murine macrophages (RAW 264.7) and human keratinocytes (HaCaT) in vitro and on the surface burn model in mice. The animal research protocols were approved by the Ethics Committee on Animal Use of the Federal University of Ceará (CEUA-UFC) under no. 8862290518.The superficial burns were performed in female swiss mice (1 cm2), and daily topical treatment was performed with the dermatological creams: base cream (Vehicle), positive control with Sulfadiazine silver 1% (Sulfa), cream containing fraction 0.5% DFSO-M and 1.0% (w/w) (CrDFSO-M 0.5 and 1.0%). In this study, the DFSO-M fraction showed low cytotoxicity in L929, RAW 264.7 and HaCaT.It also demonstrated antioxidant effect by the DPPH method and was able to protect fibroblasts from oxidative stress induced by H2O2. In RAW 264.7 macrophages, DFSO-M (25 - 100 μg/mL) did not alter nitrite levels produced after LPS stimulation (100 ng/mL), but modulated the release of proinflammatory cytokines (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10 and TGF-β). The proliferation and migration of HaCaT keratinocytes was stimulated by DFSO-M (25 and 50 μg/mL) in in vitro healing assays. However, DFSO-M did not alter the expression of the E-cadherin adhesion molecule in keratinocytes.CrDFSO-M promoted a greater contraction of the wounds after 3, 5, 7 days of treatment, stimulating the reorganization of the extracellular matrix and deposition of collagen. In addition, it reduced levels of TNF-α and increased IL-1β and IL-10 after 3 days of treatment, modulating inflammation and favoring re-epithelialization. Therefore, the healing effect of the DFSO-M fraction can be attributed to the reduction of damage caused by oxidative stress, the modulation of inflammation without interfering with tissue remodeling, as well as stimulating the re-epithelization of superficial burns.Thus, it is believed that the antioxidant, anti-inflammatory and healing potential of the fraction obtained from leaves of S. obtusifolium supports further studies that enable the development of a herbal product indicated for the treatment of wounds and burns.