Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD mice

Abstract

Naturally-occurring bioactive flavonoids such as diosmin significantly reduces amyloid beta (Aβ) associated pathology in Alzheimer’s disease (AD) mouse models. In the present study, oral administration of diosmin reduced cerebral Aβ oligomer levels, tau-hyperphosphorylation and cognitive impairment in the 3xTg-AD mouse model through glycogen synthase kinase-3 (GSK-3) and transient receptor potential canonical 6-related mechanisms. Diosmetin, one major bioactive metabolite of diosmin, increased inhibitory GSK-3β phosphorylation, while selectively reducing γ-secretase activity, Aβ generation, tau hyperphosphorylaion and pro-inflammatory activation of microglia in vitro, without altering Notch processing. Therefore, both diosmin and diosmetin could be considered as potential candidates for novel anti-AD therapy.

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

“…Similar mechanism with microglia activation along with existing cellular stress and chronic inflammation has significant role in the pathophysiology of neurodegenerative diseases [8,114]. In AD and ALS patients, abnormal phosphorylation of proteins has been observed and intriguingly, IL-1 positive microglia also found in such pathologies, which confers the putative role of inflammatory mediators in neurodegenerative pathology [116,117]. Moreover, it's been always consistent that, neuroinflammation accompanied with oxidative stress exerts detrimental consequence in chronic neurodegenerative disease profile.…”

Electroacupuncture reduces scopolamine-induced amnesia via mediating the miR-210/SIN3A and miR-183/SIN3A signaling pathway

“…In addition, several compounds derived from plants show promising e cacy in augmenting cognitive behaviors by blocking the functions of scopolamine. As a result, the above mentioned compounds have been tested in animal models to treat memory loss [20]. Interestingly, EA therapies can rescue long-term impairments of memory functions in rats suffering from dementia by protecting the integrity of neuron cells while reducing the expression levels of Noxa, bax, and P53 in rat hippocampus [21,22].…”

Electroacupuncture reduces scopolamine-induced amnesia via mediating the miR-210/SIN3A and miR-183/SIN3A signaling pathway

“…In addition, several compounds derived from plants show a promising e cacy in augmenting cognitive behaviors by blocking the functions of scopolamine. As a result, the above-mentioned compounds have been tested in animal models to treat memory loss [20]. Interestingly, EA therapies can rescue long-term impairments of memory functions in rats suffering from dementia by protecting the integrity of neuron cells while reducing the expression of Noxa, Bax, and P53 in rat hippocampus [21,22].…”