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, cucurbit[7] uril (CB[7]), 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 CB[7], 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 CB[7]. This discovery may lead to a novel AH formulation for improved safety of this natural product.