基于系统药理学解析林下山参联合米糠脂肪烷醇抗疲劳的作用机制

Anti-fatigue mechanism of mountain cultivated ginseng and rice bran fatty alkanol based on system pharmacology

目的初步探讨林下山参联合米糠脂肪烷醇抗疲劳的物质基础和作用机制。方法采用组合效应系数方法评估林下山参联合米糠脂肪烷醇抗疲劳协同增效作用;通过小鼠负重游泳实验评估林下山参联合米糠脂肪烷醇抗疲劳的功效,并测定与疲劳相关的多个体内指标,探索抗疲劳可能的作用机制;通过液相-质谱联用主要成分和入血成分分析,结合网络药理学初步解析林下山参联合米糠脂肪烷醇抗疲劳的可能作用机制与药效物质基础。结果林下山参联合米糠脂肪烷醇的组合效应系数在0.6~0.8,具有中等协同增效作用;林下山参联合米糠脂肪烷醇可以延长小鼠力竭游泳的时间,降低血浆中尿素氮和乳酸的含量和脑组织中5-羟色胺的含量,升高肝糖原和肌糖原的储备水平。成分分析表明,共有9个主要原形成分吸收入血。进一步通过网络药理学分析发现,其主要通过干预Serotonergic synapse通路发挥抗疲劳功效,4个入血的人参皂苷及三十二碳脂肪烷醇、三十碳脂肪烷醇、二十八碳脂肪烷醇可能是抗疲劳的药效成分。结论林下山参联合米糠脂肪烷醇可以通过调控多靶点、多途径实现抗疲劳功效,为两者的进一步开发和应用提供依据。

Objective To preliminarily determine the functional material basis and anti-fatigue mechanism of mountain cultivated ginseng and rice bran fatty alkanol.Methods The combination index was used to evaluate the synergistic effect of mountain cultivated ginseng and rice bran fatty alkanol on fatigue.The anti-fatigue effect of mountain cultivated ginseng and rice bran fatty alkanol was evaluated by a loading swimming experiment.Multiple indexes related to anti-fatigue were determined to explore the underlying mechanism.The anti-fatigue mechanism and effective compounds of mountain cultivated ginseng and rice bran fatty alkanol were determined by liquid chromatography-mass spectrometry based chemical constituents,absorbed components analysis,and network pharmacology.Results The combination indexes of mountain cultivated ginseng and rice bran fatty alkanol ranged 0.6~0.8,indicating moderate synergism.Mountain cultivated ginseng and rice bran fatty alkanol prolonged the exhaustive swimming time of the mice,reduced the content of urea nitrogen and lactic acid in the serum as well as 5-hydroxytryptamine in the brain tissue,and increased the reservation levels of liver glycogen and muscle glycogen,indicating anti-fatigue effect.Component analysis identified 9 main prototypes in the blood sample.Further network pharmacology analysis indicated that mountain cultivated ginseng and rice bran fatty alkanol exerted an anti-fatigue effect mainly through regulating the serotonergic synapse signaling pathways.Four ginsenosides in the plasma and thirty-two fatty alkanol,thirty triacontanol,twenty-eight ctacosanol could be active against fatigue components.Conclusion The anti-fatigue effect of mountain cultivated ginseng and rice bran fatty alkanol follows“multiple targets,multiple pathways”action mode,which may provide the theoretical basis for further development and applications of both drugs.