Interactions Between N-Terminal Extracellular Tail of CCR4 and Natural Products of Licorice Using Capillary Electrophoresis

Abstract

Licorice is gaining popularity because of its significant biological anti-inflammatory activity, while CC chemokine receptor 4 (CCR4) has been identified as a potentially important drug target for the treatment of inflammatory diseases. Capillary electrophoresis was developed for screening for the first time of CCR4 antagonists from natural products of licorice. The interactions between natural products of licorice and ML40, the equivalent peptide derived from the N-terminal of CCR4, were determined. Twenty-eight ingredients were isolated and the results showed that ten of them interacted with ML40 compared with the positive control S009. The binding constants of the compounds to ML40 were calculated and the binding constant of liquiritin apioside (LA) was the largest among them (3.636 ± 0.2185) × 104 M−1. The CCR4 antagonisms of the compounds that showed strong integration with ML40 were also confirmed by chemotaxis inhibition in which they displayed different degrees of inhibition to CCL22/CCL17-induced HEK293 chemotaxis. The methodology presented could be applied to automated high-throughput screening of potential antagonists of CCR4. This study provided the potential rationale for the development of anti-inflammatory compounds from natural products of licorice.