GLYCATION INHIBITORS AND PROBIOTICS CAN AMELIORATE THE CHANGES CAUSED BY HIGH FRUCTOSE FEED

Objective: To evaluate the use of protein glycation inhibitors and probiotics to ameliorate secondary complications in diabetes and to improve gut microbiota respectively in high fructose fed Wistar rat.Methods: The study was conducted on male Wistar rats for 7 d. Blood glucose levels in oral glucose tolerance test (OGTT) were measured using glucometer, serum parameters were analyzed using commercial kits, antioxidant status was evaluated by measuring superoxide dismutase (SOD) and catalase (CAT) levels, total reactive oxygen species were estimated using a fluorescent 2', 7'-dichlorofluorescin diacetate (DCF-DA) dye, and tissue fluorescence of liver, kidney and intestine were measured using a spectrofluorimeter.Results: OGTT pattern shows significant increase in blood glucose of fructose fed rats i.e. 154 mg/dl while, in aminoguanidine (AMG) treated and gut microbiota modulated animals it is 137 and 119 mg/dl resp. after 30 min on glucose administration. Marked reduction was found in SOD 6.37 and 11.25 U/mg of protein and catalase 186 and 65.5 U/mg of protein in liver and kidney of fructose fed animals when compared to fructose+AMG and fructose+EUGI. There is 5-6 fold significant increase in general and specific tissue fluorescence of liver and kidney, and 2.2 fold increase in liver reactive oxygen species was observed in fructose fed group as compare to control animals. Significantly higher glycation was found in intestine of fructose fed animals (general fluorescence 2.1 and specific fluorescence 3.1 AU/mg), more than that of diabetic control rats (general fluorescence 0.9 and specific fluorescence 1.6 AU/mg), represented an evidence for adverse impact of excess fructose on healthy gut.Conclusion: The use of protein glycation inhibitor and use of pre and probiotics significantly improved the serum parameters and would prevent progression to secondary complications

Synthesis and evaluation of analgesic, anti-asthmatic activity of (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 ones

Abstract Seventeen (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 one derivatives were synthesized via aldol condensation of substituted benzaldehydes with quinoline chalcones starting from 8-hydroxy quinoline. Molecular docking studies were performed on COX-2 protein for analgesic activity and PDE 4 enzyme for anti-asthmatic activity. Docking studies for analgesic activity reveal that the compounds 2 , 4 , 12 , 14 , and 15 showed significant interaction in terms of hydrogen bonding, hydrophobic attachment and van der Waal interaction with COX-2. The docking studies and pharmacological screening indicate that substitution of hydroxyl and conjugated ketone groups on the aldehyde ring and the quinoline ring accelerates analgesia with better binding to active site. Eddy's hot plate method was used to evaluate analgesic activity of the synthesized compounds. Compounds showed a substantial increase in reaction time when compared with standard pentazocin. Compounds 2 , 4 , 7 , 9 and 13 showed significant binding interactions with PDE 4 enzyme and hence were selected for evaluation of anti-asthmatic activity using the goat tracheal chain method. Studies reveal that substitution of the methoxy group at 4th & 5th positions for compounds 2 , 4 & 7 leads to significant percentage inhibition of histamine induced contraction. The synthesized compounds are thus found to be potent as analgesic and anti-asthmatic agents

Biogenic synthesis of gold nanoparticles using Argemone mexicana L. and their cytotoxic and genotoxic effects on human colon cancer cell line (HCT-15)

Abstract Background Nanomedicine has evolved as precision medicine in novel therapeutic approach of cancer management. The present study investigated the efficacy of biogenic gold nanoparticles synthesized using Argemone mexicana L. aqueous extract (AM-AuNPs) against the human colon cancer cell line, HCT-15. Results Biosynthesis of AM-AuNPs was determined by ultraviolet-visible spectroscopy and further characterized by transmission electron microscopy, X-ray diffraction, and Fourier transition infrared spectroscopy analysis. The cytotoxic activity of AM-AuNPs was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, whereas genotoxicity was evaluated by the DNA fragmentation assay. The expression of apoptosis regulatory genes such as p53 and caspase-3 was explored through semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting to evidence apoptotic cell death in HCT-15 cells. Biogenic AM-AuNPs inhibited cell proliferation in HCT-15 cell line with a half maximal inhibitory concentration (IC50) of 20.53 μg/mL at 24 h and 12.03 μg/mL at 48 h of exposure. The altered cell morphology and increased apoptosis due to AM-AuNPs were also evidenced through nuclear DNA fragmentation and upregulated expression of p53 and caspase-3 in HCT-15 cells. Conclusion The AM-AuNPs may exert antiproliferative and genotoxic effects on HCT-15 cells by cell growth suppression and induction of apoptosis mediated by activation of p53 and caspase-3 genes