Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials.

Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in Aß production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood-brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer's disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin/IGF-1 signaling pathway.

Sea grapes extract improves blood glucose, total cholesterol, and PGC-1α in rats fed on cholesterol- and fat-enriched diet.

Background: Sea grapes or  Caulerpa racemosa have a lot of phytochemical content, especially unsaturated fatty acids that are beneficial for health. This study aims to evaluate the effects of sea grapes extract on blood glucose levels, total cholesterol-, and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α in male Wistar rats, which were given per-oral (p.o.) cholesterol- and carbohydrates fat-enriched diets (CFED). Methods: Forty male Wistar albino rats weighing between 200 - 250 g were used for this study. Animals were randomly distributed into four groups of ten animals each. Group A served as control (received standard dry pellet diet). Rats in group B were fed on CFED for 4 weeks.  Groups C and D were fed on CFED and were administered 150 and 450 mg/kg of  sea grapes extract (p.o.), respectively. Results: Group C rats indicated a blood glucose reduction and an increase in PGC-1α serum, in comparison to group D (p<0.05). There were no significant differences between group C and D in blood cholesterol reduction (high dose of the extract did not have significant effects) (p=0.222), and both groups had the same effect in lowering total cholesterol in rats.  Conclusion: Sea grapes extract is proven to improve blood glucose, total cholesterol, and PGC-1α levels in rats fed with CFED.