The Ameliorative Impact of Centella Asiatica on Working Memory Deficit in STZ-Induced Rat Model of Alzheimer’s Disease

Alzheimer's disease (AD) is a complex neurodegenerative disorder with a progressive template leading to neural damage as well as cognitive and memory deficit. The present study designed to investigate the neuroprotective effects of Centella Asiatica (CA) in STZ-induced rat model of memory impairment and neuronal damage. ICV infusion of STZ (3 mg/kg) or saline (as vehicle) were performed on days 1 and 3. CA (150 and 300 mg/kg/day) was administered through oral gavage for 21 days after model induction. Y-maze test was carried out to assess working memory related performances of animals. Rats were then sacrificed and the hippocampi were harvested for evaluation of neuronal density in CA1, CA2, CA3, and DG regions using stereology technique. ICV infusion of STZ caused significant working memory impairment in Y-maze apparatus as indicated with a significant decrease in alternative behavior compared to control animals (40.67 ± 2.04 vs. 73.00 ± 1.88, p < 0.0001). Oral administration of CA (150 and 300 mg/kg each day) for 21 days significantly (55.33 ± 3.34 and 57.17 ± 3.81 vs. 40.67 ± 2.04, p < 0.013, p < 0.004) improved STZ-induced working memory deficit. Furthermore, 21 days consecutive administration of CA significantly ameliorated STZ-induced neuronal loss in the CA1, CA2, and DG subfields of the hippocampus. Overall, these data demonstrate that CA increases neuronal density and improves cognitive impairment in STZ- induced rat model of AD, thereby has a promising therapeutic potential for neurodegenerative disorders. Accordingly, further studies are needed to determine the exact molecular mechanism of CA protective effects in brain disorders particularly AD

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Ameliorative effect of sansoninto on sleep disturbance and spatial memory impairment in an Alzheimer's disease rat model

Traditional & Kampo Medicine ◽

10.1002/tkm2.1067 ◽

2017 ◽

Vol 4 (1) ◽

pp. 38-45 ◽

Cited By ~ 1

Author(s):

Hiroshi Moriyama ◽

Takuya Watanabe ◽

Kotaro Takasaki ◽

Masaki Nagao ◽

Kaori Kubota ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Spatial Memory ◽

Sleep Disturbance ◽

Rat Model ◽

Memory Impairment ◽

Ameliorative Effect

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Novel Therapeutic Mechanism of Action of Metformin and Its Nanoformulation in Alzheimer's Disease and Role of AKT/ERK/GSK Pathway.

10.21203/rs.3.rs-764206/v1 ◽

2021 ◽

Author(s):

Harish Kumar ◽

Amitava Chakrabarti ◽

Phulen Sarma ◽

Manish Modi ◽

Dibyajyoti Banerjee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Control ◽

Rat Model ◽

Memory Impairment ◽

Protective Efficacy ◽

Control Group ◽

Hyperphosphorylated Tau ◽

Days Of Therapy

Abstract Background: Insulin resistance in brain plays a critical role in the pathogenesis of Alzheimer's disease (AD). Metformin is a blood brain barrier crossing anti-diabetic insulin-sensitizer drug. Current study has evaluated the therapeutic and mechanistic role of conventional as well as solid lipid nanoformulation (SLN) of metformin in intracerebro ventricular (ICV) Aβ (1-42) rat-model of AD. Methods: SLN-metformin was prepared by the micro-emulsification method and further evaluated by zetasizer and scanning electron-microscopy. In the animal experimental phase, AD was induced by bilateral ICV injection of Aβ using stereotaxic technique, whereas control group (sham) received ICV-NS. 14 days post-model induction, ICV- Aβ treated rats were further divided into 5 groups: disease control (no treatment), Metformin dose of (50mg/kg, 100mg/kg and 150 mg/kg), SLN of metformin 50mg/kg and memantine 1.8mg/kg (positive-control). Animals were tested for cognitive performance (in EPM, MWM) after 21 days of therapy, and then sacrificed. Brain homogenate was evaluated using ELISA for (Aβ (1-42), hyperphosphorylated tau, pAKTser473, GSK-3β, p-ERK,) and HPLC (metformin level). Brain histopathology was used to evaluate neuronal injury score (H&E) and Bcl2 and BAX (IHC). Results: The average size of SLN-metformin was <200 nm and was of spherical in shape with 94.08% entrapment efficiency. Compared to sham, the disease-control group showed significantly higher (p≤0.05) memory impairment (in MWM and EPM), higher hyperphosphorylated tau, Aβ (1-42), and Bax and lower Bcl-2 expression. Metformin was detectable in brain. Treatment with metformin and its SLN form significantly decreased the memory impairment as well as decreased the expression of hyperphosphorylated tau, Aβ(1-42), Bax expression and increased expression of Bcl-2 in brain. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway can be implicated in the protective efficacy of metformin. Conclusion: Both metformin and SLN metformin is found to be effective as therapeutic agent in ICV-AB rat model of AD. AKT-ERK-GSK3β-Hyperphosphorylated tau pathway is found to be involved in the protective efficacy of metformin.

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