Prostate cell membrane chromatography-LC/MS method for screening α_1A-adrenoceptor antagonists from Lotus Plumule

The α_1A-adrenoceptor (α_1A-AR) plays an important role in drug discovery and development. An online analytical method coupling prostate cell membrane chromatography (CMC) with high-performance liquid chromatography/mass spectrometry (LC/MS) was established to screen α_1A-AR antagonists in traditional Chinese medicines (TCMs). The prostate cell membrane stationary phase (CMSP) was prepared by immobilizing the prostate cell membrane onto the surface of the silica carrier. The surface and chromatographic characteristics of the prostate CMSP were studied using tamsulosin as a model molecule. The retained fractions from the prostate CMC were analyzed by transferring them to an LC/MS system through a 10-port switch valve. The active component, which could act on the prostate cell membrane and receptor on it (such as α_1A-AR), was determined using a displacement experiment. The results indicated that liensinine, isoliensine, and neferine from Lotus Plumule exhibited similar retention characteristics to the control drug tamsulosin when utilizing the prostate CMC model. This new prostate CMC-LC/MS method is applicable for screening α_1A-AR antagonists from TCMs such as Lotus Plumule and could be employed as a drug discovery tool for natural medicinal herbs.