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Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer's drug candidates.

Gao Y, Hu YZ, Li RS, Han ZT, Geng Y, Xia Z, Du WJ, Liu LX, Zhang HH, Wang LN - Neuropsychiatr Dis Treat (2015)

Bottom Line: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice.CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde.Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, Beijing, People's Republic of China.

ABSTRACT

Background: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.

Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.

Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1(+) activated microglia in the cortex of the APP/PS1 mice.

Conclusion: Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

No MeSH data available.


Related in: MedlinePlus

Effects of CEGI on spatial learning and memory evaluated by the Morris water-maze test for 5 consecutive days of training in APP/PS1 mice.Notes:#P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A) Escape latency to reach the hidden platform in the Morris water maze; (B) swimming time within the target quadrant; (C) swimming speed during the consecutive days of training. Data presented as means ± SE, n=11–12 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.
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f1-ndt-11-537: Effects of CEGI on spatial learning and memory evaluated by the Morris water-maze test for 5 consecutive days of training in APP/PS1 mice.Notes:#P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A) Escape latency to reach the hidden platform in the Morris water maze; (B) swimming time within the target quadrant; (C) swimming speed during the consecutive days of training. Data presented as means ± SE, n=11–12 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.

Mentions: Repeated-measures ANOVA revealed a significant treatment effect (Figure 1A, P<0.05) on the escape latency. APP/PS1 mice showed significant cognitive impairment compared to the nTg group. The CEGI-L (6.6 ml/kg) group had significantly reduced escape latency compared to the Tg group (Figure 1A, P<0.05). However, the CEGI-H (13.2 mL/kg) and donepezil (2 mg/kg) groups did not have significantly reduced escape latency compared to the Tg group (Figure 1A).


Cattle encephalon glycoside and ignotin injection improves cognitive impairment in APPswe/PS1dE9 mice used as multitarget anti-Alzheimer's drug candidates.

Gao Y, Hu YZ, Li RS, Han ZT, Geng Y, Xia Z, Du WJ, Liu LX, Zhang HH, Wang LN - Neuropsychiatr Dis Treat (2015)

Effects of CEGI on spatial learning and memory evaluated by the Morris water-maze test for 5 consecutive days of training in APP/PS1 mice.Notes:#P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A) Escape latency to reach the hidden platform in the Morris water maze; (B) swimming time within the target quadrant; (C) swimming speed during the consecutive days of training. Data presented as means ± SE, n=11–12 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356454&req=5

f1-ndt-11-537: Effects of CEGI on spatial learning and memory evaluated by the Morris water-maze test for 5 consecutive days of training in APP/PS1 mice.Notes:#P<0.05, ##P<0.01 compared with the transgenic (Tg) group. (A) Escape latency to reach the hidden platform in the Morris water maze; (B) swimming time within the target quadrant; (C) swimming speed during the consecutive days of training. Data presented as means ± SE, n=11–12 mice in each group.Abbreviations: CEGI, cattle encephalon glycoside and ignotin injection; SE, standard error; H, high dose; L, low dose; APP, β-amyloid precursor protein; PS, presenilin.
Mentions: Repeated-measures ANOVA revealed a significant treatment effect (Figure 1A, P<0.05) on the escape latency. APP/PS1 mice showed significant cognitive impairment compared to the nTg group. The CEGI-L (6.6 ml/kg) group had significantly reduced escape latency compared to the Tg group (Figure 1A, P<0.05). However, the CEGI-H (13.2 mL/kg) and donepezil (2 mg/kg) groups did not have significantly reduced escape latency compared to the Tg group (Figure 1A).

Bottom Line: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice.CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde.Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

View Article: PubMed Central - PubMed

Affiliation: Institute of Geriatrics, Chinese PLA General Hospital, Beijing Key Lab of Normal Aging and Geriatrics, Beijing, People's Republic of China.

ABSTRACT

Background: Cattle encephalon glycoside and ignotin injection (CEGI), a multitargeted neurotrophic drug, has been widely used in the treatment of central and peripheral nerve injuries, such as stroke, hypoxic ischemic encephalopathy, and diabetic neuropathy in the People's Republic of China. However, data regarding the effect of CEGI on Alzheimer's disease (AD) remain scarce. The present study aimed to investigate the effect of CEGI on learning and memory in an APPswe/PS1dE9 double-transgenic mouse model, a suitable animal model of AD, and elucidate its possible mechanisms.

Materials and methods: Five-month-old APP/PS1 mice were intraperitoneally administered 6.6 mL/kg or 13.2 mL/kg of CEGI for 1 month. After 1 month of administration, all mice received Morris water maze training and a probe test. Mouse brain sections were detected by standard biochemical and immunohistochemical measures.

Results: CEGI treatment significantly improved the spatial learning and memory deficits and decreased cerebral amyloid-β42 levels in brain homogenates of APP/PS1 mice. CEGI treatment elevated the activities of superoxide dismutase, and reduced the levels of malondialdehyde. CEGI attenuated neuronal damage in the hippocampus of APP/PS1 mice and upregulated protein and gene expression of Bcl-2 and the ratio of Bcl-2/Bax. CEGI treatment decreased the number of Iba1(+) activated microglia in the cortex of the APP/PS1 mice.

Conclusion: Our results showed that CEGI prevents memory impairment, possibly by decreasing the amyloid-β42 levels in APP/PS1 mice and inhibiting oxidative stress, apoptosis, and inflammation, making CEGI a promising therapeutic agent for AD.

No MeSH data available.


Related in: MedlinePlus