Alleviation of Hepatotoxicity of Arecoline (Areca Alkaloid) by a Synthetic Receptor

摘要

Arecoline, as one of the major biologically active compounds extracted from Areca nut, has shown profound links to hepatotoxicity. In this study, the inclusion of arecoline hydrobromide (AH) in a synthetic receptor, cucurbit7 uril (CB7), was demonstrated by (HNMR)-H-1 spectroscopic titration, isothermal titration calorimetry (ITC), electrospray ionization mass spectrometry (ESI-MS), and density functional theory (DFT) molecular modeling. The results showed that AH formed 1: 1 host-guest complexes with CB7, with a binding constant K-a of 6.59 (+/- 0.23) x10(4) M-1, thermodynamically driven by both enthalpy (Delta H=-4.93 kcal mol(-1)) and entropy (TDS= 1.65 kcal mol(-1)). The hepatotoxicity of AH, when evaluated using MTT assay with a human liver cell line L02, was significantly alleviated (up to four times) upon its encapsulation by CB7. This discovery may lead to a novel AH formulation for improved safety of this natural product.