A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies.

OBJECTIVE: Natural food substances, due to high rates of antioxidants, antiviral and anti-inflammatory properties, have been proposed to have the potential for the prevention or treatment of cognitive deficits, learning and memory deficits and neuro inflammation. In particular, medicinal plants with rich amounts of beneficial components such as flavonoids are one of the most promising therapeutic candidates for the cognitive deficit and memory loss. Herein, we aimed to review the impact of medicinal plants with focus on flavonoids on cognitive dysfunction, learning and memory loss by considering their signaling pathways. METHODS: We extracted 93 preclinical and clinical studies related to the effects of flavonoids on learning and memory and cognition from published papers between 2000 and 2021 in the MEDLINE/PubMed, Cochrane Library, SCOPUS, and Airiti Library databases. RESULTS: In the preclinical studies, at least there seem to be two main neurological and biological processes in which flavonoids contribute to the improvement and/or prevention of learning, memory deficit and cognitive dysfunction: (1) Regulation of neurotransmission system and (2) Enhancement of neurogenesis, synaptic plasticity and neuronal survival. CONCLUSION: Although useful effects of flavonoids on learning and memory in preclinical investigations have been approved, more clinical trials are required to find out whether flavonoids and/or other ingredients of plants have the potent to prevent or treat neurodegenerative disorders.

Ketone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta (Aß) plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including Aß, phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and mitochondrial dysfunction appears up to 15 years before the onset of clinical AD symptoms. As glucose utilization is compromised in the brain of patients with AD, ketone bodies (KBs) may serve as an alternative source of energy. KBs are generated from the ß-oxidation of fatty acids, which are enhanced following consumption of ketogenic diets with high fat, moderate protein, and low carbohydrate. KBs have been shown to cross the blood brain barrier to improve brain energy metabolism. This review comprehensively summarizes the current literature on how increasing KBs support brain energy metabolism. In addition, for the first time, this review discusses the effects of ketogenic diet on the putative AD biomarkers such as Aß, tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism.

Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer's disease.

There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventricular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 mL/kg saline. Behavioral test (the shuttle box test) was performed on day 22 to examine learning and memory in rats. Immediately after that, hematoxylin-eosin staining was performed to observe the morphological change in hippocampal CA3 pyramidal neurons. Myricetin greatly increased the number of hippocampal CA3 pyramidal neurons and improved learning and memory impairments in rats with Alzheimer's disease. These findings suggest that myricetin is beneficial for treatment of Alzheimer's disease.