In silico analysis of Andiroba and Jambu bioactive compounds in target proteins associated with obesity and neurodegeneration

The obesity burden induces the production of pro-inflammatory molecules, which leads to higher insulin resistance risk. The insuline resistance may develoip into neurodegenerative effects, such as Tau hiperphosphorilation and beta amiloide formation, directly associated with the Alzheimer disease. Bioactive compounds, including phenolics, may present antioxidant and anti-inflammatory activities, being an interesting therapeutic option to reduce neurodegenerative effects associated to obesity. Andiroba (Carapa guianensis) and Jambu (Acmella oleracea), are two Brazilian fruit species with high phenolic and fatty acid contents. Those fruits were selected for the in silico investigation, by Molecular Docking, of the potential inhibitory activity of their main bioactive compounds (phenolic and non-phenolic) in target proteins associated with the neurodegenerative context. Bioacitve compounds (phenolic compounds: ferulic acid, chlorogenic acid, p-coumaric acid, p-hydroxybenzoic acid, protocatechuic acid, vanillic acid and naringenin; lipophilic compounds: oleic acid, linoleic acid, linolenic acid and palmitoleic acid) and target proteins (GSK3β, BACE1, STAT3, CDK5, PTP1B, PTEN, CALPAÍNA, JNK, CD36, GAP43, TNFR1 e PPARy) were selected after an extensive literature review of the fruits composition and the molecular mechanisms associated in obesity-neurodegeneration. For the phenolic compounds, the binding energies with target proteins varied from -2,17 kcal/mol to -7,50 kcal/mol, being the best interaction observed between naringenin and TNRF1 (-7,50 kcal/mol), followed by CD36 and naringenin, CD5K and chlorogenic acid and CD5K and naringenin. Amongst the phenolic compounds, naringenin, chlorogenic acid, p-coumaric acid and ferulic acid could be highlithed for their improved overall inhibition potential, when compared to the other phenolics tested. Regardless of the phenolic assayed, PTEN presented the lowests binding energies overall. Lipophilic bioactive compounds, on the other hand, presented the good inhibition potential against CDK5 and STAT3 proteins, followed by BACE1 and PTP1B proteins. Interestingly, all studied fatty acids, especially linolenic and linoleic acids, had significant interactions with tumor necrosis fator receptor 1 (TNFR1), through hydrogen bonds with the Ser-60 e Tyr-150 residues of the protein. Therefore, andiroba and jambu bioactive compounds may reduce the neurodegenerative effects associated with obesity by the inhibition of the mentioned proteins, mostly associated with the inflammation processes. This work can serve as basis for in vivo and in vitro further screenings of jambu and andiroba’s effects in the molecular mechanisms connecting the gut-brain axis.