Avaliação do potencial cicatricial de formulações tópicas contendo beta-cariofileno em lesões cutâneas de ratos
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Data
2021-08-27
Autores
Gushiken, Lucas Fernando Sérgio
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Universidade Estadual Paulista (Unesp)
Resumo
A pele é fundamental para manter a integridade do organismo. A descontinuidade desse sistema promove o mecanismo cicatricial, que pode ser dividido em fases inflamatória, proliferativa e remodeladora. As lesões cutâneas têm grande importância na saúde pública devido à possibilidade de deficiência física ou até mesmo levar à morte. Como consequência de estudos anteriores referentes à atividade cicatricial da Copaifera langsdorffii, o sesquiterpeno β-cariofileno e a óleo-resina de Copaifera langsdorffii nanoencapsulada foram selecionados para analisar o potencial cicatricial das formulações e seus mecanismos de ação. Para isso, foram utilizados ratos Wistar machos divididos em grupos experimentais (n = 5): Controle, FST, Gel, Col, Dex, NeBa, Car e NLC. Os animais foram submetidos à lesão dorsal de 3 cm de diâmetro, tratadas duas vezes por dia durante 3, 7 e 14 dias. As áreas das lesões foram medidas diariamente para verificar a redução macroscópica das lesões e amostras foram retiradas para análises de atividade anti-inflamatória, histopatológicas e imunohistoquímicas. Macroscopicamente foi possível observar a retração das lesões nos tratamentos Car e NLC comparados com FST e Gel. Os resultados de ELISA mostraram o potencial anti-inflamatório dos tratamentos Car e NLC pela redução de citocinas pró-inflamatórias TNF-α, IFN-γ, IL-1β e IL-6 e aumento da citocina anti-inflamatória IL-10. Os resultados das análises bioquímicas para estresse oxidativo mostraram o aumento de GPx nos grupos NeBa, Car e NLC. As análises histopatológicas e imunohistoquímicas mostraram o aumento da imunomarcação de laminina-γ2 e α-SMA, bem como a redução de desmogleína-3 em Car e NLC. Foi observado o aumento da deposição de colágeno nos tratamentos Car e NLC comparados a FST. Sendo assim, a partir dos resultados analisados, confirmou-se a atividade cicatricial do β-cariofileno e da óleo-resina de copaíba em lesões cutâneas, estimulando os mecanismos de retração da lesão mediado por miofibroblastos, o remodelamento da matriz extracelular e a reepitelização mediada por laminina-γ2; além de inibir a atividade inflamatória e o estresse oxidativo local.
Skin is essential to keep the organism integrity. The discontinuity of this system promotes the healing mechanism, which can be divided into inflammatory, proliferative and remodeling phases. Skin lesions are very important in public health due to the possibility of physical disability or even death. As consequence of previous studies regarding Copaifera langsdorffii healing activity, the sesquiterpene β-caryophyllene and the nanoencapsulated Copaifera langsdorffii oleo-resin were selected to analyze the healing potential of the formulations and their mechanisms of action. For this, male Wistar rats were divided into experimental groups (n = 5): Control, FST, Gel, Col, Dex, NeBa, Car and NLC. The animals were submitted to 3 cm diameter dorsal lesion, treated twice a day for 3, 7 and 14 days. Wound areas were measured daily to verify the macroscopic reduction of the lesions and samples were taken for analysis of anti-inflammatory, histopathological and immunohistochemical activities. Macroscopically, it was possible to observe wound retraction in treatments Car and NLC compared to FST and Gel. ELISA results showed the anti-inflammatory potential of Car and NLC treatments by reducing pro-inflammatory cytokines TNF-α, IFN-γ, IL-1β and IL-6 and increasing the antiinflammatory cytokine IL-10. Results of biochemical analyzes for oxidative stress showed the increase of GPx in NeBa, Car and NLC groups. Histopathological and immunohistochemical analyzes showed an increase in laminin-γ2 and α-SMA immunolabeling, as well as a reduction in desmoglein-3 in Car and NLC. An increase in collagen deposition was observed in Car and NLC treatments compared to FST. Thus, from the analyzed results, the healing activity of βcaryophyllene and copaiba oleo-resin was confirmed in skin lesions, stimulating the mechanisms of wound retraction mediated by myofibroblasts, extracellular matrix remodeling and reepithelialization mediated by laminin-γ2; besides inhibiting inflammatory activity and local oxidative stress.
Skin is essential to keep the organism integrity. The discontinuity of this system promotes the healing mechanism, which can be divided into inflammatory, proliferative and remodeling phases. Skin lesions are very important in public health due to the possibility of physical disability or even death. As consequence of previous studies regarding Copaifera langsdorffii healing activity, the sesquiterpene β-caryophyllene and the nanoencapsulated Copaifera langsdorffii oleo-resin were selected to analyze the healing potential of the formulations and their mechanisms of action. For this, male Wistar rats were divided into experimental groups (n = 5): Control, FST, Gel, Col, Dex, NeBa, Car and NLC. The animals were submitted to 3 cm diameter dorsal lesion, treated twice a day for 3, 7 and 14 days. Wound areas were measured daily to verify the macroscopic reduction of the lesions and samples were taken for analysis of anti-inflammatory, histopathological and immunohistochemical activities. Macroscopically, it was possible to observe wound retraction in treatments Car and NLC compared to FST and Gel. ELISA results showed the anti-inflammatory potential of Car and NLC treatments by reducing pro-inflammatory cytokines TNF-α, IFN-γ, IL-1β and IL-6 and increasing the antiinflammatory cytokine IL-10. Results of biochemical analyzes for oxidative stress showed the increase of GPx in NeBa, Car and NLC groups. Histopathological and immunohistochemical analyzes showed an increase in laminin-γ2 and α-SMA immunolabeling, as well as a reduction in desmoglein-3 in Car and NLC. An increase in collagen deposition was observed in Car and NLC treatments compared to FST. Thus, from the analyzed results, the healing activity of βcaryophyllene and copaiba oleo-resin was confirmed in skin lesions, stimulating the mechanisms of wound retraction mediated by myofibroblasts, extracellular matrix remodeling and reepithelialization mediated by laminin-γ2; besides inhibiting inflammatory activity and local oxidative stress.
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Palavras-chave
Cicatrização, Pele, Beta-cariofileno, Copaifera langsdorffii, Carreadores lipídicos nanoestruturados, Healing, Skin, β-caryophyllene