Screening the bioactive compound from Coptis chinensis inflorescence by immobilized peroxisome proliferator-activated receptor-gamma.

Abstract

Coptis chinensis inflorescence is a by-product of Coptis chinensis Franch and riches in alkaloids. We screened the bioactive compounds in the by-product through an immobilized peroxisome proliferator-activated receptor gamma. The receptor was covalently immobilized on the macroporous silica gel through amino groups to generate the affinity stationary phase and was applied for screening. Berberine, palmatine, and jatrorrhizine were identified as the retained components of the herb on the affinity column. We evaluated the binding of the three bioactive compounds with the receptor by nonlinear chromatography and molecular docking. The affinities of the compounds to the receptor were (1.42 ± 0.10) ×108 /M, (4.88 ± 0.38) ×107 /M, and (1.65 ± 0.13) ×107 /M for berberine, palmatine, and jatrorrhizine, with dissociation rate constants of (17.70 ± 0.03) ×10-3 /S, (5.18 ± 0.25) ×10-2 /S, and (15.7 ± 0.05) ×10-2 /S, respectively. Cys285, Arg288, Ile326, Leu330, and His449 in the agonist binding pocket of the receptor participated in the formation of bioactive compound-receptor conjugates. These data indicated that the immobilized receptor is a reliable alternative for screening the bioactive compounds. In addition, Coptis chinensis inflorescence has the potential to be a source for drug discovery.