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Journal of Integrative Neuroscience  2018, Vol. 17 Issue (3): 203-210    DOI: 10.31083/JIN-170059
Research article Previous articles | Next articles
Cognitive enhancing and antioxidant effects of tetrahydroxystilbene glucoside in Aβ1-42-induced neurodegeneration in mice
Miao Xie, Geng Zhang, Wei Yin, Xin-Xin Hei, Tao Liu*()
Teaching and Research Section of TCM Clinical Basic, Basic Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, PR China
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Abstract  

Polyhydroxy stilbenes have been reported to possess various biological activities and have potential for treatment of Alzheimer's disease. Tetrahydroxystilbene glucoside is one of the major polyhydroxy stilbenes, which provides the underlying therapeutic activities for neuroprotective actions in various experimental conditions. This study investigates the impact of a tetrahydroxystilbene glucoside remedy for cognitive disorder and oxidative stress in Aβ1-42-induced Alzheimer's disease mice and clarifies the mechanisms of action through the Kelch-like erythroid cell-derived protein with conserved non-coding homology-associated protein 1/nuclear factor erythroid 2-related factor pathway. It was found that the swimming time of Aβ1-42-induced mice treated with tetrahydroxystilbene glucoside (30, 60, and 120 mg/kg) was significantly increased in the target quadrant of a Morris water maze experiment and the number of avoidances was increased during a passive avoidance experiment, Moreover, tetrahydroxystilbene glucoside attenuated Aβ1-42-induced memory impairment. However, the locomotor and exploratory activity of mice were not affected. Tetrahydroxystilbene glucoside clearly decreased the levels of malondialdehyde and oxidized glutathione in both hippocampus and cortex compared with the Aβ1-42-treated group, and also clearly increased the level of glutathione and activities of catalase and superoxide dismutase in those tissues. The results of this study demonstrated that tetrahydroxystilbene glucoside increased nuclear factor erythroid 2-related factor and heme oxygenase-1 protein expression and decreased Kelch-like erythroid cell-derived protein with conserved non-coding homology-associated protein 1 protein expression in a concentration-dependent manner in Aβ1-42-treated mice, which involved the Kelch-like erythroid cell-derived protein with conserved non-coding homology-associated protein 1/nuclear factor erythroid 2-related factor antioxidant pathway in hippocampus and cerebral cortex tissue. These results demonstrate that tetrahydroxystilbene glucoside as a natural drug that may provide a potential treatment for Alzheimer's disease.

Key words:  Tetrahydroxystilbene glucoside      Alzheimer's disease      β-amyloid;      Keap1/Nrf2 pathway      oxidative stress     
Accepted:  23 October 2017      Published:  15 August 2018     
*Corresponding Author(s):  Tao Liu     E-mail:  taoliu60@126.com

Cite this article: 

Miao Xie, Geng Zhang, Wei Yin, Xin-Xin Hei, Tao Liu. Cognitive enhancing and antioxidant effects of tetrahydroxystilbene glucoside in Aβ1-42-induced neurodegeneration in mice. Journal of Integrative Neuroscience, 2018, 17(3): 203-210.

URL: 

https://jin.imrpress.com/EN/10.31083/JIN-170059     OR     https://jin.imrpress.com/EN/Y2018/V17/I3/203

Table 1  Effect of tetrahydroxystilbene glucoside on escape latency time (seconds) of Aβ1-42-treated mice in a spatial probe trial Morris water maze test.
Groups 1st day 2nd day 3rd day 4th day
Normal control 73.35 ± 4.29 70.72 ± 4.18 38.65 ± 2.04 25.71 ± 1.45
1-42-treated 79.95 ± 3.78 79.47 ± 3.83# 64.62 ± 3.20## 59.75 ± 3.25##
Donepezil + Aβ1-42 80.01 ± 4.45 79.26 ± 4.11 50.22 ± 2.71* 24.92 ± 1.41**
TSG30 + Aβ1-42 79.77 ± 3.92 79.35 ± 3.98 54.38 ± 2.85* 30.71 ± 1.72**
TSG60 + Aβ1-42 79.38 ± 4.01 78.92 ± 4.34 52.05 ± 2.66* 27.44 ± 1.67**
TSG120 + Aβ1-42 79.57 ± 4.73 78.79 ± 4.16 48.97 ± 3.01** 24.69 ± 1.38**
Fig. 1.  Effect of tetrahydroxystilbene glucoside on performance of Aβ1-42-treated mice in a Morris water maze test. NC: control, without treatment; Aβ1-42-treated: received 1.0 mg/ml Aβ1-42 3 $ \mu $l; Donepezil Aβ1-42: received Aβ1-42 donepezil (10 mg/kg), ICV; TSG30 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (30 mg/kg), ICV; TSG60 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (60 mg/kg), ICV; TSG120 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (120 mg/kg), ICV. Results are expressed as the mean S.E.M., $ {n} = 10 $. $^{\#\#} p < $ 0.01, compared with the NC group; $^{\ast\ast} p < $ 0.01, vs. Aβ1-42-treated group.

Fig. 2.  Effect of tetrahydroxystilbene glucoside on Aβ1-42-treated mice in a passive avoidance test. Latency time (seconds) to enter dark compartment was recorded. NC: control, without treatment; Aβ1-42-treated: received 1.0 mg/ml Aβ1-42 3 $ \mu $l; Donepezil Aβ1-42: received Aβ1-42 donepezil (10 mg/kg), ICV; TSG30 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (30 mg/kg), ICV; TSG60 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (60 mg/kg), ICV; TSG120 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (120 mg/kg), ICV. Results expressed as mean S.E.M., $n = 10$. $^{\#\#}p < $ 0.01, compared with the NC group; $^{\ast}p < $ 0.05, $^{\ast\ast}p < $ 0.01, vs. Aβ1-42-treated group.

Table 2  Effect of tetrahydroxystilbene glucoside on biochemical variables indicative of hippocampus in Aβ1-42-treated mice.
Groups MDA nmol/mg protein GSH nmol/mg protein GSSG nmol/mg protein CAT U/mg protein SOD U/mg protein
Normal control 2.5 + 0.12 10.8 + 0.57 0.23 + 0.01 24.5 + 1.23 79.1 + 4.29
Aftwtreated 4.6+ 0.23## 5.3 + 0.28## 0.52 + 0.03## 15.8 + 0.82## 24.0+1.31##
Donepezil + Aβ1-42 2.7 + 0.13** 10.2 + 0.62** 0.27 + 0.02** 22.7 + 1.31** 72.4 + 3.75**
TSG30 +Aβ1-42 3.6+ 0.17** 6.9 + 0.37* 0.40 + 0.02** 18.3 + 1.05* 51.6 + 2.66**
TSG60 +Aβ1-42 3.1 + 0.21** 8.7 + 0.49** 0.34+ 0.02** 21.6+1.14** 67.9 + 3.69**
TSG120 +Aβ1-42 2.5 + 0.14** 9.7 + 0.46** 0.29 + 0.01** 23.4 + 1.07** 75.3 + 4.02**
Table 3  Effect of tetrahydroxystilbene glucoside on biochemical variables indicative of cerebral cortex in Aβ1-42-treated mice.
Groups MDA nmol/mg protein GSH nmol/mg protein GSSG nmol/mg protein CAT U/mg protein SOD U/mg protein
Normal control 3.7 + 0.20 11.5 + 0.56 0.21 + 0.01 22.6+1.17 83.2 + 4.67
Aftwtreated 6.1 + 0.32## 5.9 + 0.31## 0.50 + 0.03## 14.7 + 0.85## 44.3 + 2.58##
Donepezil + Aβ1-42 4.4+ 0.23** 10.7 + 0.59** 0.28 + 0.01** 21.3 + 1.06** 78.0 + 3.42**
TSG30 +Aβ1-42 5.3 + 0.27* 7.4 + 0.41* 0.44 + 0.03* 17.9 + 0.92** 61.5 + 3.39**
TSG60 +Aβ1-42 4.7 + 0.24** 9.2 + 0.48** 0.37 + 0.02** 20.8 + 1.09** 69.7 + 4.11**
TSG120 +Aβ1-42 4.2+ 0.25** 10.3 + 0.50** 0.32 + 0.02** 21.5 + 0.93** 80.3 + 4.38**
Fig. 3.  Tetrahydroxystilbene glucoside activates Keap1/Nrf2 pathway in mouse hippocampus with or without Aβ1-42. NC: control, without any treatment; Aβ1-42-treated: received 1.0 mg/ml Aβ1-42 3 $ \mu $l; Donepezil Aβ1-42: received Aβ1-42 donepezil (10 mg/kg), ICV; TSG30 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (30 mg/kg), ICV; TSG60 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (60 mg/kg), ICV; TSG120 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (120 mg/kg), ICV. Results expressed as mean S.E.M. $^{\#\#}$p $ < $ 0.01, compared with the NC group; $^{\ast}p < $ 0.05, $^{\ast\ast}p < $ 0.01, vs. Aβ1-42-treated group.

Fig. 4.  Tetrahydroxystilbene glucoside activates Keap1/Nrf2 pathway in mouse cerebral cortex with or without Aβ1-42. NC: control, without any treatment; Aβ1-42-treated: received 1.0 mg/ml Aβ1-42 3 $ \mu $l; Donepezil Aβ1-42: received Aβ1-42 donepezil (10 mg/kg), ICV; TSG30 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (30 mg/kg), ICV; TSG60 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (60 mg/kg), ICV; TSG120 Aβ1-42: received Aβ1-42 tetrahydroxystilbene glucoside (120 mg/kg), ICV. Results are expressed as mean S.E.M. $^{\#\#}p < $ 0.01, compared with the NC group; $^{\ast}p < $ 0.05, $^{\ast\ast}p < $ 0.01, vs. Aβ1-42-treated group.

Fig. 5.  The schematic pathway.

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