Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Wong, Jia Hui; Muthuraju, Sangu; Reza, Faruque; Senik, Mohd Harizal; Zhang, Jingli; Yeo, Nor Aqilah Binti Mohd Yusuf; Chuang, Huei Gau; Jaafar, Hasnan; Yusof, Siti R.; Mohamad, Habsah; Muhammad, Tengku Sifzizul Tengku; Ismail, Nor Hadiani; Husin, Siti Sarwana; Abdullah, Jafri Malin

doi:10.1016/j.biopha.2018.11.044

Cited by 23 publications

(17 citation statements)

References 54 publications

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“…The authors argued that the insignificant effect of the extract at the doses of 100 and 600 mg/kg might be because the Morris water maze task required more cognitive demand than the bidirectional T-maze task. Although, in this later experiment, all high doses of the extract enhanced expressions of AMPAR and NMDAR subunits, there were differential expressions of AMPAR and NMDAR subunits in different hippocampal subregions (CA1 and CA3) and entorhinal cortex 33 . All of these effects of the extract especially at the high doses might have to be further examined in more detail.…”

Section: Discussionmentioning

confidence: 52%

Inverted U-shaped response of a standardized extract of Centella asiatica (ECa 233) on memory enhancement

Boondam

Songvut

Tantisira

et al. 2019

Sci Rep

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The herb Centella asiatica has long been considered a memory tonic. A recent review found no strong evidence for improvement of cognitive function, suggesting negative results were due to limitations in dose, standardization and product variation. We used a standardized extract of C. asiatica (ECa 233) to study behavioral, cellular and molecular effects on learning and memory enhancement. ECa 233 (10, 30, and 100 mg/kg) was given orally to normal rats twice a day for 30 days. We used the Morris water maze to test spatial learning and performed acute brain slice recording to measure changes of synaptic plasticity in the hippocampus, a core brain region for memory formation. Plasticity-related protein expressions (NR2A, NR2B, PSD-95, BDNF and TrkB) in hippocampus was also measured. Rats receiving 10 and 30 mg/kg doses showed significantly enhanced memory retention, and hippocampal long-term potentiation; however, only the 30 mg/kg dose showed increased plasticity-related proteins. There was an inverted U-shaped response of ECa 233 on memory enhancement; 30 mg/kg maximally enhanced memory retention with an increase of synaptic plasticity and plasticity-related proteins in hippocampus. Our data clearly support the beneficial effect on memory retention of a standardized extract of Centella asiatica within a specific therapeutic range.

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Section: Discussionmentioning

confidence: 52%

Inverted U-shaped response of a standardized extract of Centella asiatica (ECa 233) on memory enhancement

Boondam

Songvut

Tantisira

et al. 2019

Sci Rep

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“…no. AuRins-MIA-1-0) [24,52] was made available by Prof. Mohd Ilham Adenan from Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Technology Mara, Puncak Alam, Malaysia. All other chemicals used were of analytical grades.…”

Section: Methodsmentioning

confidence: 99%

“…Further, the neuroprotective and cognitive enhancing effects of CA is well documented on in vitro and in multiple rodents’ models of neurodegenerative diseases as well as in the settings of cognitive impairments due to variety of neurotoxic insults [19,20,21,22,23]. It has been recently reported that CA improves learning and memory in rats by increasing expression of, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 and GluA2 subunits, and NMDAR GluN2B subunits, while reducing the N -methyl- d -aspartate receptor (NMDAR) GluN2 A subunits in their hippocampus and entorhinal cortex [24]. The present study describes the effectiveness of CA in preventing d -gal/AlCl 3 mediated AD-like neurotoxicity in rats via PP2A/GSK-3β and apoptosis pathways.…”

Section: Introductionmentioning

confidence: 99%

Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer’s Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus

Chiroma

Baharuldin

Taib

et al. 2019

IJMS

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat’s hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.

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“…The chemical donepezil hydrochloride was purchased from Esai Co. Ltd. (Tokyo, Japan), D-gal and AlCl 3 were bought from Sigma Aldrich (St. Louis, MO, USA), while CA extract (Reference number: AuRins-MIA-1-0) [27,28] was obtained from Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknology Mara (UiTM) Puncak Alam, Selangor, Malaysia. Enzyme-linked immunosorbent assay (ELISA) kits for AChE, SOD, and P-Tau were purchased from Elabscience (Houston, TX, USA), while MDA kit was purchased from Cayman Chemical Company (Ann Arbor, MI, USA).…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl3 via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level

Chiroma

Baharuldin

Taib

et al. 2019

Toxics

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

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Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Cited by 23 publications

References 54 publications

Inverted U-shaped response of a standardized extract of Centella asiatica (ECa 233) on memory enhancement

Inverted U-shaped response of a standardized extract of Centella asiatica (ECa 233) on memory enhancement

Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer’s Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus

Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl3 via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level

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