Estudio del potencial inhibitorio sobre Lipasa Pancreática de los constituyentes químicos provenientes de Piper Asperiusculum (piperaceae)

Abstract

Pancreatic lipase (PL) is a key enzyme in fat absorption; thus, its inhibition represents a relevant therapeutic strategy for treating obesity. However, the only approved drug with this mechanism, Orlistat®, presents adverse effects. In this context, species from the Piper genus have shown inhibitory activity against PL, although the specific compounds responsible for this action are still unknown. Therefore, this study aims to contribute to the search for molecules with potential inhibitory effects against PL by chemically characterizing the inflorescences of Piper asperiusculum. The methodology included the fractionation of the ethanolic extract from P. asperiusculum inflorescences, purification of compounds through flash chromatography, and identification of the isolated compounds using spectroscopic methods. Subsequently, the extract, fractions, and some compounds were evaluated using a colorimetric enzymatic assay against PL, with 4-nitrophenyl dodecanoate as the substrate and Orlistat® as the positive control. As a result of the extract’s fractionation, four fractions of different polarities were obtained: DCM (73.4 g), AcOEt (31.4 g), IPA (26.5 g), and EtOH/H₂O (31.7 g). The chemical study of the DCM fraction led to the isolation of six chemical compounds, of which four were identified: a phenylpropanoid known as myristicin (Pa1), a fatty acid known as linoleic acid (Pa2), a chromene identified as 2,2-dimethyl-8-(3',3'-dimethylallyl)-2H-1-benzopyran-6-carboxylic acid (Pa3), a dihydrochalcone dimer known as piperaduncin C (Pa4), and a sterol mixture composed of campesterol, stigmasterol, and γ-sitosterol (MPa1). Except for the phenylpropanoid and the sterol mixture, the other compounds (Pa2 to Pa4) are reported for the first time in this species. Regarding inhibitory activity, the extract showed 67.0 ± 2.3% activity. Among the fractions, EtOH/H₂O and AcOEt showed the highest inhibitory activity, with values of 60% and 50%, respectively. Compound-level evaluation was conducted for Pa1 and Pa3, both of which showed inhibitory activity, with values of 65% and 84%, respectively. The IC₅₀ values were 39.76 ± 3.65 µM for Pa1 and less than 0.0012 µM for Pa3. This study is considered the first report to quantify the percentage of inhibition of the extract, fractions, and some isolated compounds against PL, validating the preliminary activity previously reported in the literature for the extract. These findings highlight the potential of P. asperiusculum as a source of natural compounds with promising PL inhibitory activity.