In silico analysis of the ADMET profile of the chemical constituents present in a hydroethanolic extract of the leaves of Embaúba (Cecropia pachystachya Trécul)

Abstract

Embaúba (Cecropia pachystachya Trécul) is a tree native to Brazil, whose leaves have traditionally been used to treat respiratory, inflammatory, and gastrointestinal disorders. These biological activities are attributed to phenolic acids and flavonoids, including chlorogenic acid, epicatechin, isoorientin/orientin, and rutin. This study aimed to identify these compounds in the hydroethanolic extract (HE) of Embaúba and perform an in silico analysis of their pharmacokinetic parameters using the PreADMET^® (Prediction of Absorption, Distribution, Metabolization, Excretion, and Toxicity) software. The chromatographic analysis confirmed the presence of the five compounds, as evidenced by co-elution with reference substances. The compounds exhibited weak interactions with plasma proteins and limited penetration across the blood-brain barrier, except for epicatechin. They demonstrated good permeability through the skin, facilitating their passage from the stratum corneum to deeper tissues. Additionally, these compounds showed low to moderate absorption and permeability in CaCo-2 cells, indicating their potential for human intestinal absorption. Although they did not inhibit P-glycoprotein, they were found to inhibit the isoenzymes CYP2C19 and CYP2C9. Additionally, chlorogenic acid, epicatechin, and isoorientin exhibited mutagenic effects in the Ames test. In conclusion, given the significant therapeutic potential of Embaúba, in silico assays should be employed to predict the pharmacokinetic profiles of its compounds, thereby facilitating and expediting the development of new drugs and reducing costs, time, and failures in the process.