Systems-pharmacology Investigation Of The Mechanisms Of Traditional Chinese Medicine Rhodiola Rosea L. For The Remission Of Fatigue

Fatigue is the most common metabolic disorder that imparts a considerable burden to health care system around the world.Traditional Chinese Medicine(TCM),such as Rhodiola rosea L.,characterized as multiple compounds and targets have been acknowledged with folk prescription in remitting fatigue,which attract abundant attention although their specific mechanisms of action are still vague.In this work,the systems pharmacology-based method which integrates pharmacokinetic filtering,target fishing and network analysis is used and exemplified by a probe,i.e.Rhodiola rosea L.,a widely clinically used anti-fatigue herbal in China.In addition,we explore and verify the mechanism through experimental method.The main results are as follows:(1)A total of 171 compound molecules were collected from the Rhodiola rosea L.,molecular database,and 16 pharmacokinetic potential active molecules were obtained after pharmacokinetic screening.(2)Target prediction and GO function enrichment analysis found that 16 potential compounds act on 219 candidate targets,109 potential therapeutic targets were obtained after screening.And these targets are related with oxidation reduction process,steroid hormone mediated signaling pathway,positive regulation of mitochondrial depolarization,synaptic transmission-dopaminergic,steroid metabolic process.etc.(3)Drug-target network analysis found that the active ingredients of Rhodiola rosea L.acts on 109 fatigue related targets in a synergistic manner,such as ADCY5,TUBB2 B,and HSD11B1.(4)The target-pathway network analysis found that the potential therapeutic targets of Rhodiola rosea L.play anti-fatigue effect mainly through metabolic pathways,serotonin pathway,PI3K-Akt signaling pathway,and calcium signaling pathway.(5)Anti-fatigue pathway network analysis found that Rhodiola rosea L.mainly through participation in the neuromodulation module,antioxidant module and energy metabolism regulation module,exert anti-fatigue effect.(6)The fatigue remitting mechanism was further verified through experiments.It was found that antioxidant therapy is an effective method to relieve fatigue.In summary,the method used in this work provides a distinct illustration for systematically understanding the mechanisms of Rhodiola rosea L.to remit fatigue,which will give an urge to the fatigue drug development and facilitate the application of traditional Chinese herbs in modern medicine.