OBJECTIVE: To evaluate the protective effect of Shouzhangshen(Rhizoma Gymnadeniae Crassinervidis) extract against acute high altitude hypoxia-induced brain injury in mice.METHODS: Sixty C57BL/6J mice were selected and assigned to six groups(n = 10): normal control group, low-pressure hypoxia group, positive control group(dexamethasone 500 mg/kg), and three groups treated with Shouzhangshen extract(250,500, and 750 mg/kg, respectively). The Morris water maze test was performed to evaluate alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuron damage. Hypoxia-inducible factor(HIF)-1α, interleukin(IL)-1β, tumor necrosis factor(TNF)-α, vascular endothelial growth factor(VEGF), and malondialdehyde(MDA) expression in brain tissue and serum,as well as superoxide dismutase(SOD) and glutathione(GSH) activity in brain tissues were measured by enzyme-linked immunosorbent assays, quantitative real-time-polymerase chain reaction and western blots.RESULTS: The Morris water maze test results showed that Shouzhangshen extract can significantly reduce the latency and swimming distance to escape onto a visible platform, increase neuron density and hierarchy and the number of pyramidal neurons, and decrease the expression of HIF-1α,IL-1β, TNF-α, and VEGF m RNAs and proteins in both brain tissue and serum(P < 0.05). Furthermore, significantly lower MDA expression and higher GSH activity were detected in the three groups treated with Shouzhangshen compared with the low-pressure hypoxia group(P < 0.05). However, no significant alteration was observed for SOD activity(P >0.05).CONCLUSION: Our findings suggest that Shouzhangshen extract may have a significant effect on acute high altitude hypoxia-induced brain injury in mice.