DL-3-n-Butylphthalide Improves Physical and Cognitive Performance of Animals with Acute and Chronic Hypobaric Hypoxia

Abstract Background: Studies revealed the protective effect of DL-3-n-butylphthalide (NBP) against ischemic hypoxia diseases. However, the role of NBP in animals with hypobaric hypoxia is elusive. This study investigated the effect of NBP on animals with acute and chronic hypobaric hypoxia.Methods: SD rats and Kunming mice administrated with NBP (90, 180 and 360 mg/kg for mice, and 60, 120, and 240 mg/kg for rats) were located in 10,000 m hypobaric hypoxia chamber. And survival analysis of animals implied that NBP could significantly improve survival percent at 30 min. Then, treated animals were evaluated for exhaustive time and exhaustive distance in forced exercise wheel-track treadmill and treadmill running experiments at 5,800 m for 3 or 21 days, to evaluate physical functions. Rats were also evaluated for times of active escape, average time of active escape, time of passive escape, and average time of passive escape in a shuttle-box experiment at 5,800 m for 7 or 28 days, to evaluate cognitive functions. ATP level was evaluated in the gastrocnemius muscle and maloaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), lactate, and glutathione peroxiase (GSH-Px) measurements and routine blood tests were detected.Results: Exhaustive time for rats (NBP, 120 and 240 mg/kg) and exhaustive time and distance for mice (NBP, 90 mg/kg) significantly increased under acute hypoxia. And NBP treatment significantly increased the exhaustive time for rats under chronic hypoxia. Moreover, NBP of 120 and 240 mg/kg significantly increased the average time of passive escape under acute and chronic hypoxia. These results suggested that NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px increased under acute and chronic hypoxia. Furthermore, the content of ATP significantly increased, while lactate level significantly decreased. The results presented that NBP could regulate redox homeostasis and improve energy metabolism.Conclusion: NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia by increasing anti-oxidative capacity and energy supply.