基于“功效成分群”动态传递规律的盘龙七片质量标志物(Q-Marker)筛选

Screening of Panlongqi Tablets quality markers based on“functional component group”dynamic transmission pattern

目的基于盘龙七片“祛风除湿”抗炎功效,通过分析盘龙七片“功效成分群”在“饮片-成药-入血成分”间传递的动态规律,筛选出质量标志物(quality markers,Q-Marker)。方法采用超高效液相-四极杆-飞行时间质谱联用技术(UPLCQ-TOF-MS/MS)对盘龙七片化学成分群进行表征,根据前期网络药理学分析结果,筛选候选“功效成分群”并以多重反应监测(MRM)模式建立同时定量测定方法。进一步通过评估功效成分群在“饮片-成药-入血成分”间转移规律确定“功效成分群”组成,然后以虚拟分子对接技术筛选候选Q-Marker,最后以“成分-体外活性”关联算法分析候选Q-Marker与关键靶点的结合活性,确定能代表盘龙七片“祛风除湿”抗炎作用的Q-Marker。结果成分表征鉴定并确定得到44个化学成分,结合网络药理学分析选择其中24个成分作为候选“功效成分群”。进一步评估“饮片-成药-入血”间动态传递规律筛选出7个转移率较高成分。最后通过分子对接及“成分-活性”关联算法确定了6个成分作为盘龙七片“祛风除湿”抗炎功效的QMarker。结论综合盘龙七片化学成分表征、“饮片-成药-入血”间转移规律、关键靶点结合能力和体外活性关联分析结果,将去氢木香内酯、龙胆苦苷、木香烃内酯、β-蜕皮甾酮、迷迭香酸和染料木素6个化合物作为盘龙七片Q-Marker。

Objective To screen quality markers(Q-Marker)of Panlongqi Tablets(盘龙七片,PT)by analyzing the dynamic law of the transmission of its“functional component group”between“decoction piece-prescription medicine-blood component”,based on its anti-inflammation effects of“dispelling wind and dampness”.Methods The UPLC-QTOF-MS/MS technique was used to analyze the chemical constituents of PT,then according to our previous study of network pharmacologic analysis,the“functional component group”was pre-selected.After that,an MRM scan mode of UPLC-MS/MS was employed for the simultaneous quantitative methodology.Moreover,the“functional component group”was selected based on their dynamic transmission pattern in“decoction piece-prescription medicine-blood component”.Furthermore,the the virtual molecular docking technique was used to screen candidate Q-markers.Finally,the combination activity of candidate Q-markers and key targets was analyzed using the“compose-in vitro activity”association algorithm to identify Q-markers that can represent the anti-inflammatory effect of PT.Results A total of 44 components were characterized and identified.Aline with previously network pharmacologic prediction,24 components were selected as candidate“functional component group”.After“decoction piece-prescription medicine-blood component”transmission analysis,seven components were screened with high transmission rate.Following the molecular docking and“compose-activity”regression calculation,six components were screened as the final Q-Marker that can represent the anti-inflammatory effect of“dispelling wind and dampness”of PT.Conclusion Based on the chemical composition characterization of PT,the transfer rule between“decoction piece-prescription medicine-blood component”,the binding ability of key targets and the correlation analysis results of in vitro activities,the dehydrocostus lactone,gentiopicroside,costunolide,β-ecdysone,rosmarinic acid and genistein were selected as Q-Marker of PT.