Estudo fitoquímico das folhas e galhos de Endlicheria paniculata e avaliação das atividades biológicas dos extratos e neolignanas

Abstract

Endlicheria paniculata is a fruit tree in the Lauraceae family, native to Amazon Rainforest, Atlantic Forest, and Cerrado. In this study, the identification of the chemical composition of the hexane and methanolic extracts of leaves (EHF and EMF) and branches (EHG and EMG) of this species were evaluated. In addition, the antioxidant potential and the levels of total phenols, flavonoids, and proanthocyanidins were evaluated, showing low values for all. High-performance liquid chromatography (CLAE) analyzes showed the presence of two major compounds in EHF and EHG, which were isolated and identified as O-methyldehydrodieugenol B (I) and dehydrodieugenol B (II), two neolignans. In addition, other compounds were isolated and identified: β-sitosterol (III) present in EHG, stigmasterol (IV) present in EHF, kaempferol (V) present in EMG, and palmitic acid (VI) present in EMF. The compounds were characterized by 1H and 13C NMR and by gas chromatography coupled with mass spectroscopy (GC–MS) through similarity indices. Through GC–MS analysis, it was possible to identify fatty acids, esters, neolignans, phenylpropanoids, sesquiterpenes, and steroids present in EHF and EHG. Neolignans I and II were evaluated for the inhibitory activity of α-glucosidase and pancreatic lipase enzymes, and for glycation inhibitory activity, in all cases, the neolignans showed low inhibition. Neolignans I and II were also analyzed by molecular docking with enzymes cyclooxygenases 1 and 2 (Cox-1 and Cox-2) to assess their anti-inflammatory potential and the results were compared to those obtained for commercial drugs. Given the promising results of molecular docking, the in vivo anti-inflammatory activity (chronic inflammation induced by sponge implants in black mice - C57Bl/6) of EHF, EHG, I, and II was evaluated at dosages of 10, 100, and 1000 ng. Treatment of mice with EHF had anti-inflammatory, fibrogenic, and anti-angiogenic effects, while treatment with EHG had pro-inflammatory, anti-angiogenic, and anti-fibrogenic effects at all doses evaluated. Neolignan I had antifibrogenic and antiangiogenic effects at all doses, anti-inflammatory at a dose of 100 ng and pro-inflammatory at a dose of 1000 ng, while neolignan II had anti-inflammatory, antifibrogenic and antiangiogenic effects at all doses evaluated. The in silico analysis of the pharmacokinetic parameters of I and II support their potential as drug candidates, as they follow all the rules proposed by Lipinski, Ghose, Veber, and Egan.