Crosstalk between obesity, diabetes, and alzheimer’s disease: Introducing quercetin as an effective triple herbal medicine

Obesity and diabetes are the most common metabolic disorders, which are strongly related to Alzheimer's disease (AD) in aging. Diabetes and obesity can lead to the accumulation of amyloid plaques, neurofibrillary tangles (NFTs), and other symptoms of AD through several pathways, including insulin resistance, hyperglycemia, hyperinsulinemia, chronic inflammation, oxidative stress, adipokines dysregulation, and vascular impairment. Currently, the use of polyphenols has been expanded in animal models and in-vitro studies because of their comparatively negligible adverse effects. Among them, quercetin (QT) is one of the most abundant polyphenolic flavonoids, which is present in fruits and vegetables and displays many biological, health-promoting effects in a wide range of diseases. The low bioavailability and poor solubility of QT have also led researchers to make various QT-involved nanoparticles (NPs) to overcome these limitations. In this paper, we review significant molecular mechanisms induced by diabetes and obesity that increase AD pathogenesis. Then, we summarize in vitro, in vivo, and clinical evidence regarding the anti-Alzheimer, anti-diabetic and anti-obesity effects of QT. Finally, QT in pure and combination form using NPs has been suggested as a promising therapeutic agent for future studies.