Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol.

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.

Can We Treat Neuroinflammation in Alzheimer's Disease?

Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.