Exosomes: current knowledge and future perspectives.

Exosomes are membrane-bound micro-vesicles that possess endless therapeutic potential for treatment of numerous pathologies including autoimmune, cardiovascular, ocular, and nervous disorders. Despite considerable knowledge about exosome biogenesis and secretion, still, there is a lack of information regarding exosome uptake by cell types and internal signaling pathways through which these exosomes process cellular response. Exosomes are key components of cell signaling and intercellular communication. In central nervous system (CNS), exosomes can penetrate BBB and maintain homeostasis by myelin sheath regulation and the waste products elimination. Therefore, the current review summarizes role of exosomes and their use as biomarkers in cardiovascular, nervous and ocular disorders. This aspect of exosomes provides positive hope to monitor disease development and enable early diagnosis and treatment optimization. In this review, we have summarized recent findings on physiological and therapeutic effects of exosomes and also attempt to provide insights about stress-preconditioned exosomes and stem cell-derived exosomes.

Norbixin, an apocarotenoid derivative activates PPARγ in cardiometabolic syndrome: Validation by in silico and in vivo experimental assessment.

The increased prevalence of cardio-metabolic disorders worldwide prompted the exploration of new strategies for its treatment. Peroxisome Proliferator activated receptor (PPAR) play major role in regulation of lipid as well as glucose metabolism and thus, natural PPARγ activators seem to be drug of choice. AIMS: In the present work, we studied norbixin which is a natural apocarotenoid derivative for its agonistic activity for PPAR γ followed by in vivo studies for amelioration of cardio-metabolic syndrome (CMetS). MAIN METHODS: The methods include computational studies, TR-FRET binding analysis and in vivo studies on high fat diet induced rats. KEY FINDINGS: Molecular docking and molecular dynamics (MD) simulation studies showed that norbixin could be embedded into hydrophobic pocket of PPARγ and stable hydrogen bonding interactions were found with residues Glu273, Tyr327, Ser289, His323, His449 and Tyr473 of PPARγ. These results were substantiated by significant in vitro PPAR agonistic activity of norbixin in TR-FRET binding assay studies. The experimental results of norbixin in high fat diet induced CMetS in rats further confirmed that norbixin decreased insulin resistance (IR), hyperglycemia and dyslipidemia. These results were accompanied by reduced inflammatory marker hs-CRP as well as decreased oxidative stress and arterial pressure. The histopathology of heart sections also showed that norbixin could prevent the abnormal fibrotic changes in heart. Furthermore, PPARγ protein expressions were increased, whereas NF-κB expression was decreased by norbixin treatment in western blot studies. SIGNIFICANCE: These results validate norbixin as a novel PPARγ agonist and prove therapeutic potential of norbixin in treatment of CMetS.