Amelioration of perivascular adipose inflammation reverses vascular dysfunction in a model of nonobese prediabetic metabolic challenge: potential role of antidiabetic drugs.

The onset of vascular impairment precedes that of diagnostic hyperglycemia in diabetic patients suggesting a vascular insult early in the course of metabolic dysfunction without a well-defined mechanism. Mounting evidence implicates adipose inflammation in the pathogenesis of insulin resistance and diabetes. It is not certain whether amelioration of adipose inflammation is sufficient to preclude vascular dysfunction in early stages of metabolic disease.

Tackling neuroinflammation and cholinergic deficit in Alzheimer's disease: Multi-target inhibitors of cholinesterases, cyclooxygenase-2 and 15-lipoxygenase.

Neuroinflammation and cholinergic deficit are key detrimental processes involved in Alzheimer's disease. Hence, in the search for novel and effective treatment strategies, the multi-target-directed ligand paradigm was applied to the rational design of two series of new hybrids endowed with anti-inflammatory and anticholinesterase activity via triple targeting properties, namely able to simultaneously hit cholinesterases, cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX) enzymes. Among the synthesized compounds, triazoles 5b and 5d, and thiosemicarbazide hybrid 6e emerged as promising new hits, being able to effectively inhibit human butyrylcholinesterase (hBChE), COX-2 and 15-LOX enzymes with a higher inhibitory potency than the reference inhibitors tacrine (for hBChE inhibition), celecoxib (for COX-2 inhibition) and both NDGA and Zileuton (for 15-LOX inhibition).