Objective To explore the protective effects of citrus tangerine pith extract on memory impairment in hypoxic mice. Methods Thirty male BALB/c mice were randomised into normoxia control (CON), hypoxia model (HYP) and citrus tangerine pith extract (CIT) groups, with 10 mice in each group. The latter two groups were placed in a low-pressure oxygen chambers at an altitude simulating 6,000 meters for 8 hours per day for 28 days. The CON group and the HPY group were given 0.4 ml of pure water by gavage, and the CIT group was given 15 mg/(kg·bw) of citrus tangerine pith extract. Shuttle experiment and step-down test were used to assess the active and passive learning and memory abilities. Hematoxylin-eosin staining was used to observe the morphological changes in hippocampus tissue. Biochemical methods were used to determine LDH and ATPase activity in brain tissue. The metabolites of the glycolytic and tricarboxylic acid cycles in brain tissue were identified using metabonomics. Results Compared with the CON group, mice in the HYP group showed a looser arrangement of neurons in the hippocampus and an increase in the nuclear consolidation. In the shuttle experiment, the number of active shuttles was significantly decreased (P<0.05), and the number of non-responses was significantly increased (P<0.05). In the step-down test, the number of errors was significantly increased (P<0.05) and the latency was significantly shortened (P<0.05). The contents of ATP, PEP, aconitrate, isocitrate, KGA, SA, and OA were decreased (P<0.05), while the contents of LA, D-G6P, β-D-F6P and F1,6P were increased (P<0.05). The LDH and ATPase activities of brain tissues in the HYP group were significantly lower (P<0.05). Compared with the HYP group, citrus tangerine pith extract significantly elevated the number of active shuttles in the shuttle experiment (P<0.05) and decreased the number of non-responses (P<0.05). In the step-down test, the number of errors was significantly reduced (P<0.05) and the latency was significantly prolonged (P<0.05). Citrus tangerine pith extract improved the cell morphology and tightness of arrangement in the hippocampus. The contents of ATP and PEP were elevated (P<0.05), and the contents of LA, D-G6P, β-D-F6P and F1,6P were reduced (P<0.05). The LDH activity in citrus tangerine pith extract group was lowered (P<0.05), and the ATPase was enhanced (P<0.05). Conclusion Citrus tangerine pith extract can ameliorate memory impairment in hypoxic mice, which is related to the modulation of brain energy metabolism.
Key words
hypoxia /
citrus tangerine pith extract /
mice /
memory impairment /
energy metabolism
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