CARNOSINE-LOADED ORAL NIOSOMES AMELIORATE HIGH-FRUCTOSE-INDUCED METABOLIC SYNDROME IN RATS VIA MODULATION OF SIRT1, A METABOLIC MASTER SWITCH

Abstract

Metabolic syndrome is a crucial health challenge, and the available therapeutic agents are still not effective. Carnosine, a cytoplasmic dipeptide, is a potent anti-glycation, anti-oxidant, anti-inflammatory and chelating agent. However, whether carnosine would be assumed as a potential hypoglycemic agent or not, no decisive report with detailed mechanisms is found yet. As such, we suggest the carnosine-loaded in niosomes as a prospective solution to bypass its unwanted fast degradation by carnosinase which is considered as a major obstacle with the clinical application of carnosine as an oral drug therapy. Toward this, the purpose of our study is to assess the profits of oral administration of carnosine, and carnosine-loaded niosome in HFD-induced metabolic syndrome rats and to inspect some of the involved mechanisms. Initially, carnosine-loaded niosomes were prepared and characterized. Then, metabolic syndrome was provoked by 60% fructose diet in male Sprague Dawley rats where carnosine and carnosine-loaded niosomes were orally administered at doses 50 mg/kg and 25 mg/kg, respectively. In addition, biochemical and molecular studies were performed to clarify the possible mechanisms of action. Data showed that the consumption of 60% fructose diet displayed a tremendous increment in body weight, body mass index as well as a significant elevation in levels of serum glucose, insulin, TAG, TC, LDL-c, VLDL-c and FFA. Also, it showed a significant reduction in levels of serum HDL-c. Furthermore, HFD provoked up-regulation of SREBP-1c and FAS mRNA levels in adipose tissue. Also, it induced down-regulation of SIRT1, GLUT-4 mRNA levels in adipose tissue. We found that oral administration of either carnosine or carnosine-loaded niosome effectively reversed HFD-mediated alterations via SIRT1 activation. Overall, oral delivery of carnosine-loaded niosome had a better efficacy than oral carnosine, attenuating HFD-mediated alterations. Carnosine nano-formulation is a new excellent candidates for metabolic syndrome management and needs further exploration of its mechanisms.