No abstract

No abstract

No abstract

No abstract

No abstract

No abstract

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 (Aβ1-42), and phosphorylated tau protein (p-tau) count, and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukine-1beta (IL-1β), 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. Graphical abstract

Alzheimer’s disease is among the challenging diseases to social and healthcare systems because no treatment has been achieved yet. Although the ambiguous pathological mechanism underlying this disorder, ion channel dysfunction is one of the recently accepted possible mechanism. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in cellular excitability and synaptic transmission. Ivabradine (Iva), an HCN blocker, is acting on HCN channels, and is clinically used for angina and arrhythmia. The current study aimed to investigate the therapeutic effects of Iva against scopolamine (Sco) induced dementia. To test our hypothesis, Sco and Iva injected rats were tested for behavioural changes, followed by ELISA and histopathological analysis of the hippocampus. Induced dementia was confirmed by behavioural tests, inflammatory cytokines and oxidative stress tests and histopathological signs of neurodegeneration, multifocal deposition of congo red stained amyloid beta plaques and the decreased optical density of HCN1 immunoreactivity. Iva ameliorated the scopolamine-induced dysfunction, the hippocampus restored its normal healthy neurons, the amyloid plaques disappeared and the optical density of HCN1 immunoreactivity increased in hippocampal cells. The results suggested that blockage of HCN1 channels might underly the Iva therapeutic effect. Therefore, Iva might have beneficial effects on neurological disorders linked to HCN channelopathies.