Revisão bibliográfica dos efeitos biológicos das principais arnicas brasileiras, e avaliação da toxicidade oral e efeito cicatrizante tópico da arnica brasileira, Lychnophora ericoides Mart (Asteraceae), no tratamento de feridas cutâneas em modelo animal

Abstract

Natural products have contributed for years to the development of modern medicine and continue to play an important role in the discovery of bioactive molecules. The therapeutic potential of plant species has been the focus of several studies in order to prove the therapeutic efficacy and safety. Following this perspective, the species popularly known as Brazilian arnica or false arnica, especially Lychnophora ericoides Mart, have demonstrated important biological activities such as anti-inflammatory and analgesic, evidenced both in popular culture and in the scientific community. Given the above, this thesis aimed to present a review of the main biological effects, geographic distribution and potential uses described in the literature for nine species popularly known as Brazilian arnica. Furthermore, we sought to evaluate the oral toxicity of the ethanolic extract of L. ericoides leaves and its therapeutic potential in tissue repair in cutaneous wounds. For the review, nine species most used in folk medicine, such as “arnica” were considered: Calea uniflora, Chaptalia nutans, Lychnophora ericoides, L. pinaster, L. salicifolia, Porophyllum ruderale, Pseudobrickellia brasiliensis, Solidago chilensis, Sphagneticola trilobata. According to literature data, the species are distributed across the Cerrado, Caatinga, Atlantic Forest, Pampa, Pantanal and Amazon biomes. They are effective in the treatment of pain in inflammatory processes, corroborating with popular knowledge Despite having important activities such as antioxidant, leishmanicidal, antimicrobial and healing, it is noted that there are gaps in the literature mainly regarding the molecular mechanism of action and the safety of use of some species and their isolated compounds. In this sense, the assessment of acute toxicity followed the protocol of the Organization for Economic Cooperation and Development (OECD) 423, in which a single dose of 50, 300 and 2000 mg/kg of L. ericoides extract was orally administered to female Swiss mice. The animals were observed for 14 days. Subacute toxicity followed the OECD 407 protocol, in which doses of 50, 300 and 500 mg/kg of the extract were administered daily for 28 consecutive days by oral gavage in male and female Swiss mice. Clinical signs, water and food consumption, blood count, serum biochemical analysis and organ histopathology were evaluated. In the acute toxicity study, histopathological changes were observed in the liver, kidney, lung and spleen at all doses evaluated. Continuous administration of the extract at doses of 50, 300 and 500 mg/kg did not result in mortality. Continuous administration of the extract at doses of 50, 300 and 500 mg/kg did not result in mortality. However, white blood cell counts in both sexes increased significantly, as did alkaline phosphatase dosage in males treated with 500 mg/kg of extract. Histopathological examination of liver, kidney, spleen, lung and heart showed degenerative features, with foci of inflammatory infiltrates. The results showed that the oral use of the extract can develop changes in several organs, therefore, its oral administration is not indicated. Despite the oral toxicity, the therapeutic properties of the species can be exploited for other purposes, such as its topical use for the treatment of cutaneous wounds. For this, male C57BL/6 mice were randomized into four groups, which received the following topical treatments for 14 days: Negative control- NC (vehicle); Positive control- PC (Kollagenase®+chloramphenicol); Ethanol extract L. ericoides 5% -EELE 5; Ethanol extract L. ericoides 10% -EELE 10. The effect on healing was assessed by analyzing wound closure kinetics, histological analysis of scar tissue collected on days 3, 7 and 14 of treatment, analysis of angiogenesis, mast cell count, re epithelialization and collagenization. In addition to evaluating the expression of healing marker genes. The results showed cutaneous wounds treated with EELE 10% had their healing process accelerated, with adequate healing resolution, fewer mast cells, greater collagen deposition and increased expression levels of collagen I mRNA, endothelial growth factor vascular A (VEGF-A) and basic fibroblast growth factor (FGF-2). In summary, we report for the first time that L. ericoides accelerates the wound healing process and is therefore a potential topical healing agent for skin wounds.