Amelioration Of Phenylethanoid Glycosides To Operation Efficiency And Its Mechanism In High Altitude

Objective1.To screen out the anti-exercise fatigue activity of three phenylethanoid glycosides in hypoxia environment and elucidate its possible mechanism.2.To explore the amelioration of verbascoside on hypoxia-induced memory impairment and its possible mechanism.Methods1.By the rats exhausted-swimming in a large hypobaric chamber,with the swimming time,energy storage substances,metabolic enzymes,and metabolites as indexes,the anti-fatigue activities and mechanism of verbascoside,echinacoside and crenatoside(150 mg/kg,Po.,1/Day)on exhausted-swimming were studied in a hypoxic environment.2.After memory exercise,the Wistar rats were adminstered with the best anti-fatigue active phenylethanoid glycoside(50,150,300 mg/kg,Po.,1/Day)for four days and then were placed in a large hypobaric chamber to simulate the exposition of hypobaric hypoxia environment(7500 m,3 days).The rats were adminstered every day under 4000 m for another 3 days.Before the exposition,memory capability was tested with the eight-arm maze;after the exposition,memory capability was tested again under 4000 m and the rats were decapitated.The contents of malondialdehyde(MDA),reduced glutathione(GSH),and the activity of total superoxide dismutase(T-SOD)in plasma,brain,and hippocampus were determined.RT-PCR was used to detect the mRNA expression of mTOR,P70S6 K,and 4E-BP1,and the protein expressions of p-mTOR,p-P70S6 K,p-4E-BP1,and Caspase-3 in hippocampus were tested with Western Blotting.Results1.Compared with the hypoxic model group,the phenylethanoid glycoside groups could prolong the swimming time of rats and there was statistical difference in the verbascoside group(P<0.05);the edema and inflammatory infiltration of liver and skeletal muscle cells were ameliorated in phenylethanoid glycoside groups and the effect was significant in verbascosidegroup;the level of energy storage substances was increased;positive effect on the metabolism-related enzyme activity and and metabolites could be found;the decomposition of proteins was reduced.The effect was significant in verbascoside group.2.Compared with the hypoxic model group,the working memory error,reference memory error,total errors,and total time were obviously reduced in verbascoside groups;the neurons in the rat hippocampus arranged orderly and the phenomenon of nuclear condensation was less in verbascoside groups;the contents of MDA in plasma,brain,and hippocampus were significantly decreased,content of GSH and activity of T-SOD were significantly increased in verbascoside groups;the mRNA and protein expressions of mTOR and P70S6 K in the hippocampus were raised;while the mRNA expression of 4E-BP1,the protein expression of 4E-BP1 and Caspase-3 were decreased in verbascoside groups.ConclusionThe phenylethanoid glycosides,especially verbascoside,are very potential with anti fatigue activity and amelioration on the hypoxia-induced memory impairment.The mechanism may be explained with regulation of energy metabolism,decrease of oxidative stress,activation of mTOR signaling pathway.Verbascoside exhibited a prospect to elevate operation efficiency in high altitude.