ABSTRACT
INTRODUCTION: Consumption of highly processed calories dense diet leads abrupt increase in postprandial blood glucose level, which in turn induces immediate oxidative stress. Postprandial hyperglycemia (PPHG) and resultant oxidative stress is one of the earliest detectable abnormalities in diabetes prone individuals, independent risk factor for development of cardiovascular disorders (CVD), a major pathophysiological link between diabetes and CVD and an important contributing factor in atherogenesis even in non-diabetic individuals. Therefore, dietary supplements mitigating PPHG spikes along with potent antioxidant activities may help decrease development of PPHG and oxidative stress induced pathogenesis. OBJECTIVES: The study evaluated free radicals scavenging, antioxidant properties and intestinal α-glucosidase inhibitory activity in methanol extract of two varieties of Cicer arietinum Linn viz. Bengal gram and Kabuli chana and green gram (Vigna radiata Linn. Wilczek) raw grains and their sprouts and studied their influence on starch-induced postprandial glycemic excursion in rats. MATERIALS AND METHODS: Healthy grains were procured from local markets. Free radicals scavenging antioxidant and glucose-induced hemoglobin (Hb)-glycation inhibition activities were analyzed using standard in vitro procedures. In vitro antihyperglycemic activity was evaluated by assessing rat intestinal α-glucosidase inhibitory activity. Influence on starch-induced postprandial glycemic excursion in rats was studied by pre-treatment of rats with extracts. RESULTS: Compared with raw seeds increase in total polyphenol and flavonoids concentration in green gram sprouts and Kabuli chana sprouts (KCs) were observed. Total protein concentrations in sprouts did not differ from non-sprouted grains. 2,2'- Azinobis (3-ethyl benzthiazoline-6-sulphonic acid) cation scavenging activity was more than twice in Bengal gram sprouts of (BGs) and KCs than their raw seeds. 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide scavenging, nitro blue tetrazolium reducing and glucose-induced Hb-glycation inhibitory activity did not differ from non-sprouted raw grains. Increase in rat intestinal α-glucosidase inhibitory activity was observed in BGs and KCs. BGs significantly mitigated 1(st) 30 min starch-induced postprandial glycemic excursions and reduced 2 h postprandial glycemic load. CONCLUSION: Sprouting leads dynamic changes in free radicals scavenging potentials and antioxidant activities in grains. Consumption of seeds as well as BGs before the starch-rich meal can significantly mitigate 1(st) 30 min postprandial glycemic excursion and reduce 2 h postprandial glycemic burden.
ABSTRACT
OBJECTIVE: Consumption of green-leafy vegetables is being advocated beneficial for type 2 diabetes mellitus individuals possibly because they are cost effective source of potent biological antioxidants. This research analyzed various phytochemicals, free radicals scavenging antioxidant potentials and starch digesting enzymes inhibitory activities in fresh juice of nine green-leafy vegetables. Furthermore, this study also investigated influence of these vegetables juice on starch and glucose induced postprandial glycemic load. MATERIALS AND METHODS: Phytochemical constituents, in vitro free radicals scavenging antioxidant and enzymes inhibitory activities were evaluated applying various reported methods. Post-prandial glycemic excursion was induced in rats pretreated with vegetables juice by oral administration of starch and glucose. RESULTS: All the leafy vegetables juice displayed potent free radicals scavenging activities. Juice of amaranthus, rumex, palak and raphanus displayed potential anti-oxidative property by reducing H2O2 induced hemolysis in rats red blood cells RBCs. Ajwain and rumex juice showed pancreatic α-amylase inhibitory activity. Alternanthera, ajwain, methi, amaranthus and sowa leaves juice displayed intestinal α-glucosidase inhibitory activity. Juice of raphanus, ajwain and sowa significantly mitigated starch-induced postprandial glycemic load. Amaranthus leaves juice potently mitigated glucose-induced postprandial glycemic load and also reduced hemoglobin glycation induced by glucose in vitro. CONCLUSIONS: This investigation finds that juice of leafy vegetables is potent source of biological antioxidants. In addition, juice of raphanus, ajwain and sowa leaves possess capacity to mitigate starch induced postprandial glycemic burden and amaranthus leaves' juice can reduce glucose induced postprandial glycemic excursion.
ABSTRACT
Chaperone protein Hsp90 maintains functional integrity and maturation of a large number of cellular proteins including transcription factors, kinases, etc. It is often over-expressed in cancer cells for simultaneous maintenance of many non-regulated and/or genetically mutated proteins. Small molecule-based regimens inhibiting over-expressing Hsp90 in cancer cells often plagued with improper targeting leading to non-specific toxicity. Recently using a glucocorticoid receptor (GR)-targeted cationic lipoplex, we observed cancer cell-specific GR-transactivation and transgene expression by utilizing an unprecedentedly compromised chaperone-activity of cancer cell-associated Hsp90. In normal cells, GR is expressed ubiquitously and is highly regulated and chaperoned by Hsp90. This does not allow cancer cell-alike GR-mediated transgene expression. As a novel anticancer strategy, we showed that compromising Hsp90 in cancer cells can be utilized to selectively deplete its own level by delivering a specially designed artificial miRNA-plasmid against Hsp90 (amiR-Hsp90). Practically, GR-mediated delivery of amiR-Hsp90 plasmid in tumor-bearing mice, depleted Hsp90, critically down-regulated levels of Akt, VEGFR2 and other Hsp90-client proteins but up-regulated wild-type p53 in tumor. These enforced apoptosis in angiogenic vessels and in tumor mass and significantly shrunk tumor-volume. The present study describes gene therapy strategy against Hsp90 using a new GR-targeted liposome-amiR-Hsp90 lipoplex formulation for treating cancer.
