Research On New Anti-fatigue Agents Based On Combining Strategy And Arctigenin Derivatives

Fatigue refers to the physiological state in which people cannot maintain the predetermined intensity during exercise,causing general sub-health and receiving much attention in the medical circle.In works requiring mental focus(e.g.,all kinds of driving),fatigue led mistakes are harmful to the society.In order to maximize efficiency and prevent fatigue,anti-fatigue studies focus on regulating relevant physiological mechanisms of the body with functional molecules.It is of great significance to find new anti-fatigue agents that produce instant effects with remitting efforts.This paper includes two parts with the objective of developing a new anti-fatigue agent that is highly efficient.The research methodologies of the two parts are independent,namely,the design of combination agents based on bioinformatics and the structural modification based on arctigenin that is the focus of the studies as an active ingredient and the core structure.The first part focuses on anti-fatigue combination agent based on bioinformatics,which aims to develop new kinds of such agents with rational combination strategy.Bioinformatics analysis is used to study key factors leading to physiological changes in exercise.Then a strategy that improves antioxidant activity,regulates energy metabolism,supplies glycogen storage and stimulates the central nervous system is proposed.A representative composite formulation with three natural and endogenous compounds [arctigenin(ARG),caffeine(C),and glucose(Glu)] is adopted to investigate the synergistic anti-fatigue effect.How Z-005 affects the exercise of mice in wheel running,tail suspension,suspension and bounce tests is studied.Besides,the mechanism and safety of the formulation is also discussed.Results show that Z-005 has a significant synergistic effect on deferring exercise-induced fatigue in the wheel running test,in which the exhaustion distance of Z-005 group is 2.40-fold greater than the sports control group and 1.43-fold greater than the positive control Red Bull.This is because that Z-005 stimulates the central nervous system,enhances antioxidant capacity,scavenges metabolites and maintains the glycogen to activate AMPK.These results confirm that Z-005 can delay fatigue by actions with multiple factors.These findings contribute to the discovery of potential anti-fatigue agents and novel treatments for sub-health.The second part discovers new anti-fatigue molecules based on the structural modification of arctigenin,in which compounds A and B are added to impove water solubitity and the anti-fatigue effect of arctigenin.Phenolic hydroxyl groups are modified by adding hydroxyethyl,which is a splicing arm,and functional molecules.Series A: the water solubility of arctigenin is improved by connecting different amino acids(7 compounds).Among them,the wheel running exhaustion distance of Z-A-6group is the highest(4.88-fold greater than sports control group and 1.34-fold greater than arctigenin).Series B: The structure of class B compounds is analyzed by connecting dipeptides(5 compounds),among which,the exhaustion distance of Z-B-4and Z-B-5 are the highest(3.48-fold and 3.62-fold greater than sports control group).In addition,it is found that Z-B-4 is more efficient as an antioxidant capacity booster than arctigenin.To sum up,the purpose of this project is to develop high-efficiency anti-fatigue agent.This study provides a new research idea for the development of anti-fatigue combined agent.A valuable modification method was provided for improving the water solubility and pharmacological activity of endogenous molecules with anti-fatigue activity.The two parts of work have certain reference value in the research of anti-fatigue.