Memantine versus Ginkgo biloba Extract: A Comparative Study on Cognitive Dysfunction Treatment in a Novel Rat Model.

Extracellular senile plaques and intraneuronal neurofibrillary tangles are two devastating brain proteinopathies that are indicative of Alzheimer's disease, the most prevalent type of dementia. Currently, no effective medications are available to stop or reverse Alzheimer's disease. Ginkgo biloba extract, commonly referred to as EGb 761, is a natural product made from the leaves of the G. biloba tree. It has long been demonstrated to have therapeutic benefits in Alzheimer's disease. The current study assessed the beneficial effects of EGb 761 against Alzheimer's disease in comparison with memantine, a standard treatment for Alzheimer's disease. The scopolamine-heavy metals mixture rat Alzheimer's disease model is a newly created model to study the effects of EGb 761 oral therapy on cognitive performance and other Alzheimer's disease-like changes over a 28-day experimental period. This new Alzheimer's disease model provides better criteria for Alzheimer's disease hallmarks than the conventional scopolamine model. The EGb 761 reversed memory and learning deficits induced by the scopolamine-heavy metals mixture. These outcomes were linked to a more pronounced inhibitory effect on acetylcholinesterase, caspase-3, hippocampal amyloid-beta protein (Aß1 - 42), phosphorylated tau protein counts, and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) compared to the memantine-treated group. Furthermore, EGb 761 treatment considerably reduced lipid peroxidation (malondialdehyde) and improved reduced glutathione levels compared to memantine. Our results suggest EGb 761's potential in treating central nervous system disorders. It's a promising candidate for future Alzheimer's disease therapeutic exploration. This study also highlights the need for future research to focus on the positive benefits of herbal medicines.

Protective effects of curcumin and Ginkgo biloba extract combination on a new model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative illnesses, and yet, no workable treatments have been discovered to prevent or reverse AD. Curcumin (CUR), the major polyphenolic compound of turmeric (Curcuma longa) rhizomes, and Ginkgo biloba extract (GBE) are natural substances derived from conventional Chinese herbs that have long been shown to provide therapeutic advantages for AD. The uptake of curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Meanwhile, GBE has been shown to improve BBB permeability. The present study evaluated the neuroprotective effects and pharmacokinetic profile of curcumin and GBE combination to find out whether GBE can enhance curcumin's beneficial effects in AD by raising its brain concentration. Results revealed that CUR + GBE achieved significantly higher levels of curcumin in the brain and plasma after 30 min and 1 h of oral administration, compared to curcumin alone, and this was confirmed by reversed phase high-performance liquid chromatography (RP-HPLC). The effect of combined oral treatment, for 28 successive days, on cognitive function and other AD-like alterations was studied in scopolamine-heavy metal mixtures (SCO + HMM) AD model in rats. The combination reversed at least, partially on the learning and memory impairment induced by SCO + HMM. This was associated with a more pronounced inhibitory effect on acetylcholinesterase (AChE), caspase-3, hippocampal amyloid beta (Aß1-42), and phosphorylated tau protein (p-tau) count, and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukine-1beta (IL-1ß), as compared to the curcumin alone-treated group. Additionally, the combined treatment significantly decreased lipid peroxidation (MDA) and increased levels of reduced glutathione (GSH), when compared with the curcumin alone. These findings support the concept that the combination strategy might be an alternative therapy in the management/prevention of neurological disorders. This study sheds light on a new approach for exploring new phyto-therapies for AD and emphasizes that more research should focus on the synergic effects of herbal drugs in future.

Terpenoid-rich Elettaria cardamomum extract prevents Alzheimer-like alterations induced in diabetic rats via inhibition of GSK3ß activity, oxidative stress and pro-inflammatory cytokines.

PURPOSE: Recent studies suggested that the non-familiar form of Alzheimer's disease (AD) could be consequence of metabolic syndrome and neuroinflammation. Elettaria cardamomum extract (EC) has exhibited antidiabetic, antioxidant and anti-inflammatory properties. This research was conducted to evaluate the effects of EC on AD-like alterations in rats induced by high fructose and high fat diet coupled with a single small dose of STZ (25 mg/kg) (T2DM rats). METHODS: Phytochemical analysis was carried out. Behavioral tests, immunohistochemical examination, biochemical analysis and gene expression determination were performed in treated and controls rats. RESULTS: The majority of EC compounds were terpenoids. EC extract administration for 8 weeks attenuated AD-like alterations. It reversed a T2DM-induced decline in cognitive functions in passive avoidance task and Morris water maze test. It significantly lowered the elevated hippocampal level of AChE activity and caspase-3 activity, an indicator of degeneration in T2DM rats Also, it reduced the accumulation of Aß and p-tau in the brain of T2DM rats. Furthermore, it elevated the suppressed glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). EC treatment reduced hippocampal lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system, including superoxide dismutase (SOD) and reduced glutathione (GSH). Meanwhile, it lowered hippocampal TNFα, IL ß1but not IL6 and reduced GSK-3ß in brainT2D rats. CONCLUSION: EC treatment could ameliorate AD-like alterations in T2DM rats through activation of blunted insulin signal transduction in the brain, attenuation of associated oxidative stress and neuroinflammation.

Polyphenol-rich Boswellia serrata gum prevents cognitive impairment and insulin resistance of diabetic rats through inhibition of GSK3ß activity, oxidative stress and pro-inflammatory cytokines.

Type 2 diabetes (T2D) is associated with accelerated cognitive decline. To date, there is no T2D-specific treatment to prevent or ameliorate cognitive dysfunction. Boswellia serrate (BS) gum has been shown to possess multiple pharmacological actions including anti-inflammatory, anticancer and ant- apoptotic actions. The present study was aimed to investigate the effect of BS on cognitive impairment associated with T2D induced in rats by high fat/high fructose (HF/HFr) diet with a single injection of streptozotocin (STZ) and to explore the mechanism of action. The effect of 3 doses of BS extract and the reference drug on the behavioral, biochemical, histopathological and glutamate gene expression abnormalities in T2D rates was evaluated. HF/HFr diet/ STZ induces learning and memory deficits, which were reversed by BS extract. It showed a significant decrease in Aß deposits and p-tau positive cells. BS extract also reduced significantly the hippocampal elevated levels of caspase-3, cholinesterase (ChE), GSK-3ß, TNF-α, IL-1ß, IL-6, and MDA. Moreover, BS extract enhanced significantly the suppressed hippocampal level of GSH, SOD and glutamate receptor expression (GluR, NR1, NR2 A, and NR2B). In addition, BS extract alleviated insulin resistance and hyperlipidemia of T2D rats. Our findings suggest that BS extract reversed learning and memory impairment in HF/ HFr diet / STZ induced diabetic rats. This effect may be attributed to the inhibition of insulin resistance, pro-inflammatory cytokines, oxidative stress and hyperlipidemia.