The Ameliorative Impact of Centella asiatica on the Working Memory Deficit in Streptozotocin-induced Rat Model of Alzheimer Disease

Abstract

Introduction: Alzheimer disease (AD) is a complex neurodegenerative disorder with a progressive nature leading to neural damage and cognitive and memory deficit. The present study investigated the neuroprotective effects of Centella asiatica (CA) in Streptozotocin (STZ)-induced rat model of memory impairment and neuronal damage.

Methods: The intracerebroventricular infusion of STZ (3 mg/rat) or saline (as the vehicle) was performed on days 1 and 3. CA (150 and 300 mg/kg/d) was administered through oral gavage for 21 days after model induction. We used the Y-maze test to assess the working memory-related performances of animals. Rats were then sacrificed, and their hippocampi were harvested for evaluation of neuronal density in the cornu ammonis (CA1, CA2, CA3) and Dentate Gyrus (DG) regions using stereology technique.

Results: The intracerebroventricular infusion of STZ caused significant working memory impairment demonstrated in the Y-maze apparatus, 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 improved STZ-induced working memory deficit (55.33±3.34 and 57.17±3.81 vs 40.67±2.04, P<0.013, P<0.004, respectively). Furthermore, 21 days of consecutive administration of CA significantly ameliorated STZ-induced neuronal loss in the CA1, CA2, and DG subfields of the hippocampus.

Conclusion: Overall, these data demonstrate that CA increases neuronal density and improves cognitive impairment in the STZ-induced rat model of AD, thereby having 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.

Highlights: Centella asiatica (CA) improved the STZ-induced working memory deficit.CA could prevent hippocampal neural cell loss dose-dependent manner.CA improved memory through mitigating neuronal loss in hippocampus.

Plain language summary: Memory loss is the first signs of dementia. It is well known that a healthy diet might be as good for your brain as it is for your heart. Numerous traditionally used medicinal herbs could significantly affect key events culminating in dementia and Alzheimer's disease. Centella asiatica, commonly known as Gotu Kola or Indian Pennywort, is a tropical, medicinal plant native to Southeast Asian countries. It is one of the becoming popular medicinal plants in the world. Centella asiatica (CA) is widely used in different traditional medicine systems for various purposes, such as reducing blood pressure, memory enhancement, and promoting longevity. In the present study, we tested the possible impact of CA leaf and stem extract in an animal model of memory damage. Memory impairment was induced in adult rats by intracerebral infusion of a neurotoxin chemical. Then, the memory-impaired animals were orally treated with 150-300 mg/kg of CA extract for 21 days. Finally, we tested their working memory by placing them in a Y-maze apparatus. Furthermore, their most involved brain part (hippocampus) was dissected, and its cell density was evaluated. Our findings exhibited that CA treatment considerably improved rats' memory performance, indicating by enhancing working memory score in the Y-maze task. In addition, CA treatment significantly prevented neuronal cell loss in the hippocampus of memory-impaired rats. This study shows that CA has beneficial effects on memory and cognitive function.

Keywords: Alzheimer disease; Centella asiatica; Neuron Degeneration; Working memory.

Figure 1.

Centella asiatica (CA) improved Streptozotocin (STZ)-induced working memory deficits Animals received ICV infusion of saline/STZ alone or combined with CA (150 and 300 mg/kg). CA significantly increased the alternative behavior at doses of 150 and 300 mg/kg (A). No significant difference was observed between the groups regarding the total arms entries (B). ^****P<0.0001 compared to the Control group. #P<0.01 and ##P<0.004 compared to the STZ -treated rats. Values are expressed as mean±SEM (n=6 in each group)

Figure 2.

Neuroprotective effect of Centella asiatica (CA) against Streptozotocin (STZ)-induced neurotoxicity Alteration of neuronal cell density in various subfields of the hippocampus. A: CA1, B: CA2, C: CA3, and D: DG. *P<0.001 compared to the control group. #P<0.001 compared to STZ treated rats. Values are expressed as Mean±SEM (n=6 in each group).

Figure 2.

Neuroprotective effect of Centella asiatica (CA) against Streptozotocin (STZ)-induced neurotoxicity Alteration of neuronal cell density in various subfields of the hippocampus. A: CA1, B: CA2, C: CA3, and D: DG. *P<0.001 compared to the control group. #P<0.001 compared to STZ treated rats. Values are expressed as Mean±SEM (n=6 in each group).