Advanced Glycation End Product Inhibition by Alkaloids from Ocotea paranapiacabensis for the Prevention of Skin Aging

Autor(es)

de Freitas, Larissa ; Valli, Marilia ; Dametto, Alessandra C. ; Pennacchi, Paula C. ; Andricopulo, Adriano D. ; Maria-Engler, Silvya S. ; Bolzani, Vanderlan S.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Natural Products; v. 83, n. 3, p. 8-pg., 2020-03-27.

Resumo

A bioassay-guided study aiming at identifying inhibitors of the glycation process on the leaves of Ocotea paranapiacabensis afforded four benzylisoquinoline alkaloids (1-4), with 1 and 2 identified as new naturals products, while 3 and 4 were previously described in the literature, with 3 being identified as magnocurarine. Purification was performed by column chromatography and high-performance liquid chromatography. The structures of the isolated compounds were elucidated by spectroscopic methods including UV, NMR, and HRMS. The process of skin aging has been recently associated with advanced glycation end products (AGEs), and strategies inhibiting their formation have been addressed by pharmaceutical companies for the development of novel antiaging compounds. Alkaloids 1-4 were evaluated for their potential to inhibit AGE formation and showed inhibition of 62.9%, 83.3%, 26.1%, and 98.2% (150 mu M), respectively. The antiaging potential of compounds 1 and 4 were evaluated with a reconstructed human skin model in vitro, and results showed a decrease in dermis contraction (8.7% and 4.2% respectively for 1 and 4) when compared to the glycated control (57.4%). Additionally, absorption, distribution, metabolism, and excretion (ADME) and toxicity properties were predicted using in silico methods, and the results were considered significantly promising for alkaloids 1 and 4 to continue the development of these alkaloids with skincare properties. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 19/05967-3 - Compreensão da função biológica de produtos naturais de Bases de Dados para o planejamento de compostos ativos para o tratamento de doenças infecciosas
• Beneficiário: Marilia Valli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado