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Alleviation of Hepatotoxicity of Arecoline (Areca Alkaloid) by a Synthetic Receptor
Author(s) -
Li Shengke,
Yang Xue,
Niu Yanan,
Andrew Greg L.,
Bardelang David,
Chen Xiuping,
Wang Ruibing
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700333
Subject(s) - isothermal titration calorimetry , chemistry , arecoline , areca , titration , electrospray ionization , enthalpy , stereochemistry , nuclear chemistry , chromatography , mass spectrometry , organic chemistry , receptor , biochemistry , muscarinic acetylcholine receptor , structural engineering , nut , engineering , physics , quantum mechanics
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 1 H NMR 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) ×10 4 M −1 , thermodynamically driven by both enthalpy ( Δ H=‐4.93 kcal mol −1 ) and entropy (T Δ S=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.