Jia Xiaoni, Liu Jiajun, Shi Baimei, Liang Qi, Gao Juan, Feng Gangjun, Chang Zhongman, Li Qian, Zhang Xiaohong, Chen Jianbo, Zhao Xinfeng
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, China.
Department of Pharmacy, Xi 'an Mental Health Center, Xi'an, China.
Front Pharmacol. 2019 Aug 16;10:915. doi: 10.3389/fphar.2019.00915. eCollection 2019.
As the first and key step of traditional Chinese medicine (TCM)-guided drug development, lead discovery necessitates continuous exploration of new methodology for screening bioactive compounds from TCM. This work intends to establish a strategy for rapidly recognizing β-adrenergic receptor (β-AR) target compounds from the fruit of (LHG). The method involved immobilization of β-AR onto amino-microsphere to synthesize the receptor column, the combination of the column to high-performance liquid chromatography (HPLC) to screen bioactive compounds of LHG, the identification of the compounds by HPLC coupled with mass spectrometry (MS), and the evaluation of druggability through pharmacokinetic examination by HPLC-MS/MS. Mogroside V was screened and identified as the β-AR-targeted bioactive compounds in LHG. This compound exhibited desired pharmacokinetic behavior including the time to reach peak plasma concentrations of 45 min, the relatively low elimination of 138.5 min, and the high bioavailability. These parameters indicated that mogroside V has a good druggability for the development of new drugs fighting β-AR-mediated respiratory ailments like asthma. The combination of the methods in this work is probably becoming a powerful strategy for screening and early evaluating the bioactive compounds specifically binding to G-protein-coupled receptor target from complex matrices including TCM.
作为中药导向药物研发的首要关键步骤，先导化合物发现需要不断探索从中药中筛选生物活性化合物的新方法。这项工作旨在建立一种从罗汉果（LHG）果实中快速识别β-肾上腺素能受体（β-AR）靶向化合物的策略。该方法包括将β-AR固定在氨基微球上以合成受体柱，将该柱与高效液相色谱（HPLC）联用筛选LHG的生物活性化合物，通过HPLC与质谱（MS）联用鉴定化合物，并通过HPLC-MS/MS进行药代动力学检测来评估成药性。罗汉果甜苷V被筛选并鉴定为LHG中β-AR靶向的生物活性化合物。该化合物表现出理想的药代动力学行为，包括达峰时间为45分钟，相对较低的消除时间为138.5分钟，以及高生物利用度。这些参数表明罗汉果甜苷V对于开发对抗β-AR介导的呼吸道疾病如哮喘的新药具有良好的成药性。这项工作中方法的结合可能成为从包括中药在内的复杂基质中筛选和早期评估特异性结合G蛋白偶联受体靶点的生物活性化合物的有力策略。
