基于活血功效靶标的血府逐瘀汤有效成分群辨识研究

Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function

血府逐瘀汤为活血化瘀的经典方剂,在临床上应用广泛且疗效显著,然而其发挥活血功效的物质基础尚不清晰,因此该研究基于活血功效关键靶点进行血府逐瘀汤有效成分群的辨识研究。研究通过检索中药化学成分数据库收集血府逐瘀汤化学成分,基于实验室前期获得的活血功效关键靶点构建其分子对接模型,与血府逐瘀汤成分进行对接,挑选每个靶点打分值前5且含量可测的活性成分作为方剂的潜在活血有效成分群。关键药效成分以及高含量成分为中药发挥药效的核心,中药整体活性在一定程度上可表征关键药效成分以及高含量成分的活性。研究以抗血小板聚集药效部分表征活血功效,通过寻找血府逐瘀汤潜在有效成分群的来源中药进行体内活性实验以验证有效成分群的准确性。结果显示,基于中药成分数据库筛选获得血府逐瘀汤210个化学成分,与活血功效关键靶点进行分子对接,挑选每个靶点打分值前5且含量可测的活性成分,最终选择川芎嗪、毛蕊花糖苷、柚皮苷、橙皮苷、甘草苷、新橙皮苷、羟基红花黄色素A、阿魏酸、梓醇、甘草酸作为血府逐瘀汤发挥活血功效的潜在有效成分群。将其来源中药川芎、地黄、枳壳、甘草及红花进行抗血小板聚集活性验证,血小板聚集率为9.82%±5.11%。与空白组相比,实验组可显著抑制二磷酸腺苷(adenosine diphosphate,ADP)诱导的血小板聚集(P<0.01),验证了有效成分群的准确性。该研究为血府逐瘀汤的物质基础研究提供了指导,同时也为经典名方的开发利用提供了研究思路。

As a classic prescription for promoting blood circulation to remove blood stasis,Xuefu Zhuyu Decoction(XFZYD)is widely used in clinical practice and has notable curative effect.Based on the key targets of activating blood circulation,this study identified the active components of XFZYD to reveal the material basis.The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD.The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription.The efficacy of the prescription can embody key pharmacological and high-content components.In this study,anti-platelet aggregation activity was used to characterize the effect of activating blood,and the in vivo experiments were conducted to verify the accuracy of the active components.A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood.Ligustrazine,acteoside,naringin,etc.were selected as the potential active components for activating blood in XFZYD.The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma,Rehmanniae Radix,Aurantii Fructus,Glycyrrhizae Radix et Rhizoma,and Carthami Flos was 9.82%±5.11%.Compared with that in the control group,the platelet aggregation induced by adenosine diphosphate(ADP)was significantly inhibited in the test group(P<0.01),which verified the accuracy of the active components.This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.