Protection against Alzheimer's disease by luteolin: Role of brain glucose regulation, anti-inflammatory activity, and the gut microbiota-liver-brain axis

Luteolin is a widely distributed flavone herbs and vegetables. It has anti-oxidant and anti-inflammatory activities and improves glucose metabolism by potentiating insulin sensitivity and improving beta-cell function and mass. Alzheimer's disease (AD) is induced by the deposition of amyloid-beta (A beta) in the hippocampus and the formation of neurotoxic A beta plaques. The A beta deposition is associated with increased formation of A beta from amyloid precursor protein by up-regulation of beta-secretase and beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). Furthermore, A beta accumulation is increased by brain insulin resistance. The impairment of insulin/IGF-1 signaling mainly in the hippocampus and brain insulin resistance is connected to signals originating in the liver and gut microbiota, known as the gut microbiota-liver-brain axis. This indicates that the changes in the production of short-chain fatty acids by the gut microbiota and pro-inflammatory cytokines can alter insulin resistance in the liver and brain. Luteolin is detected in the brain tissues after passing through the blood-brain barrier, where it can directly influence neuroinflammation and brain insulin resistance and modulate A beta deposition. Luteolin (10-70 mg/kg bw for rodents) can modulate the systemic and brain insulin resistance, and it suppresses AD development directly, and it influences A beta deposition by activation of the gut microbiota-liver-brain axis. In this review, we evaluate the potential of luteolin to mitigate two potential causes of AD, neuroinflammatory processes, and disruption of glucose metabolism in the brain. This review suggests that luteolin intake can enhance brain insulin resistance and neuroinflammation, directly and indirectly, to protect against the development of Alzheimer's-like disease, and the gut microbiota-liver-brain axis is mainly involved in the indirect pathway. However, most studies have been conducted in animal studies, and human clinical trials are needed.

Automated summary

Luteolin, a widely distributed flavone compound found in herbs and vegetables, has antioxidant and anti-inflammatory properties and can improve glucose metabolism. It can protect the brain from Alzheimer's disease development through modulation of insulin sensitivity, neuroinflammation, and the gut microbiota-liver-brain axis. Further research is needed to validate its effects in human clinical trials.