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. 2014 May 5;15(5):7667-83.
doi: 10.3390/ijms15057667.

Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats

Xiao-Yuan Mao  1 , Dan-Feng Cao  2 , Xi Li  3 , Ji-Ye Yin  4 , Zhi-Bin Wang  5 , Ying Zhang  6 , Chen-Xue Mao  7 , Hong-Hao Zhou  8 , Zhao-Qian Liu  9
Affiliations

Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats

Xiao-Yuan Mao et al. Int J Mol Sci. .

Erratum in

Abstract

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

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Figures

Figure 1.
Figure 1.
The chemical structure of HupA [22].
Figure 2.
Figure 2.
Effects of HupA on the escape latency (A); mean path length (B); mean percentage of time spent in the target quadrant (C); the number of times of crossing platform (D) and swimming speed (E) in control and diabetic rats (n = 8, mean ± S.D.). ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
Figure 2.
Figure 2.
Effects of HupA on the escape latency (A); mean path length (B); mean percentage of time spent in the target quadrant (C); the number of times of crossing platform (D) and swimming speed (E) in control and diabetic rats (n = 8, mean ± S.D.). ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
Figure 3.
Figure 3.
Effects of HupA on the hippocampal neuronal loss control and diabetic rats. (A) and (B) were the representative photographs of hippocampal neuronal loss and quantitative analysis of viable neurons, respectively. ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups. Scale bar: 50 μm.
Figure 4.
Figure 4.
Effects of HupA on the activities of AChE (A) and ChAT (B) in cerebral cortex and hippocampus of control and diabetic rats (n = 8, mean ± S.D.). ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
Figure 5.
Figure 5.
Effects of HupA on the mRNA (A) and protein levels (B) of BDNF in cerebral cortex and hippocampus of control and diabetic rats (n = 8, mean ± S.D.). ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
Figure 6.
Figure 6.
Effects of HupA on the oxidative stress in cerebral cortex and hippocampus of control and diabetic rats (n = 8, mean ± S.D.). (A–D) showed the oxidative production of MDA, SOD, GSH-PX and CAT activities, respectively in the cerebral cortex and hippocampus of control and diabetic rat brain. ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
Figure 7.
Figure 7.
Effects of HupA on the inflammatory cytokines in cerebral cortex and hippocampus of control and diabetic rats (n = 8, mean ± S.D.). (A–D) displayed NF κB p65 subunit, TNF-α, IL-1β and IL-6 levels in the cerebral cortex and hippocampus of control and diabetic rat brain. ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
Figure 8.
Figure 8.
Effects of HupA on the caspase-3 activity in cerebral cortex and hippocampus of control and diabetic rats (n = 8, mean ± S.D.). ** p < 0.01 compared with Con group; ## p < 0.01 compared with DM group. Con, control; DM, diabetes; DM + HupA (0.05), huperzine A (0.05 mg/kg)-treated; DM + HupA (0.1), huperzine A (0.1 mg/kg)-treated groups.
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