From Inflammation to Cutaneous Repair: Topical Application of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-kappa B, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers

Autor(es):Mostrar menos -

Beserra, Fernando Pereira ^[1] ; Sergio Gushiken, Lucas Fernando ^[1] ; Vieira, Ana Julia ^[1] ; Bergamo, Danilo Augusto ^[1] ; Bergamo, Patricia Luisa ^[1] ; de Souza, Mariana Oliveira ^[1] ; Hussni, Carlos Alberto ^[2] ; Takahira, Regina Kiomi ^[3] ; Nobrega, Rafael Henrique ^[1] ; Monteiro Martinez, Emanuel Ricardo ^[1] ; Jackson, Christopher John ^[4] ; de Azevedo Maia, Gabriela Lemos ^[5] ; Rozza, Ariane Leite ^[1] ; Pellizzon, Claudia Helena ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Morphol, BR-18618689 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Vet Med & Anim Sci, Dept Surg & Vet Anesthesiol, BR-18618689 Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Sch Vet Med & Anim Sci, Dept Clin Vet, BR-18618681 Botucatu, SP - Brazil

^[4] Univ Sydney, Kolling Inst Med Res, Royal North Shore Hosp, Sydney, NSW 2065 - Australia

^[5] Fed Univ Sao Francisco Valley UNIVASF, Dept Pharm, BR-56304205 Petrolina, PE - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 14 JUL 2020.
• Citações Web of Science: 0

Resumo

Skin wound healing is a highly complex event that involves different mediators at the cellular and molecular level. Lupeol has been reported to possess different biological activities, such as anti-inflammatory, antioxidant, antidiabetic, and in vitro wound healing properties, which motivated us to proceed with in vivo studies. We aimed to investigate the wound healing effect of lupeol-based cream for 3, 7, and 14 days. Wound excisions were induced on the thoraco-lumbar region of rats and topically treated immediately after injury induction. Macroscopic, histopathological, and immunohistochemical analyses were performed. Cytokine levels were measured by ELISA and gene expression was evaluated by real-time RT-qPCR. Our results showed a strong wound-healing effect of lupeol-based cream after 7 and 14 days. Lupeol treatment caused a reduction in proinflammatory cytokines (TNF-a, IL-1 beta, and IL-6) and gene and protein NF-kappa B expression, and positively altered IL-10 levels, showing anti-inflammatory effects in the three treatment periods. Lupeol treatment showed involvement in the proliferative phase by stimulating the formation of new blood vessels, increasing the immunostaining of Ki-67 and gene expression, and immunolabeling of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and increasing gene expression of transforming growth factor beta-1 (TGF-beta 1) after seven days of treatment. Lupeol was also involved in the tissue regeneration phase by increasing the synthesis of collagen fibers noted in the three treatment periods analyzed. Our findings suggest that lupeol may serve as a novel therapeutic option to treat cutaneous wounds by regulating mechanisms involved in the inflammatory, proliferative, and tissue-remodeling phases. (AU)

• Processo FAPESP: 13/23340-1 - Processo cicatricial em pele sob tratamento com monoterpeno (mentol) e triterpeno (lupeol) em modelos experimentais
• Beneficiário: Claudia Helena Pellizzon
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/23247-4 - Avaliação dos mecanismos celulares e moleculares do creme à base de lupeol sobre o processo de cicatrização de feridas cutâneas em modelos experimentais de ratos diabéticos e não diabéticos
• Beneficiário: Fernando Pereira Beserra
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/17600-1 - "Avaliação do potencial cicatricial de formulações tópicas contendo terpenos em lesões cutâneas de ratos"
• Beneficiário: Claudia Helena Pellizzon
• Modalidade de apoio: Auxílio à Pesquisa - Regular