title: Possible signaling cascades involved in attenuation of alloxan-induced oxidative stress and hyperglycemia in mice by ethanolic extract of Syzygium jambolanum: drug-DNA interaction with calf thymus DNA as target.
abstract: We injected alloxan (100 mg/kg b.w.) in mice (Mus musculus) intra-peritoneally to induce hyperglycemia and divided the hyperglycemic mice into two sub-groups: one was fed ethanolic extract of Syzygium jambolanum (EESJ) (20 mg/kg b.w. for 8 weeks) and the other 85% ethyl alcohol ("vehicle"-control). Chromatographic and mass spectroscopic studies of EESJ revealed two principal components, one corresponding to an iridoid glycoside. We estimated blood glucose, glycosylated hemoglobin, glucokinase, and fructosamine and analyzed the expression of marker proteins like insulin, GLUT2, and GLUT4. We also studied anti-oxidant biomarkers like lipid peroxidase, superoxide dismutase, total thiole and catalase. We assayed generation of reactive oxygen species (ROS) and several inflammatory and apoptotic signal proteins like NFkB, IFNγ, iNOS, Bcl(2,) Bax, STAT1 and Caspase3. We further evaluated the effects of hyperglycemia on DNA through comet assay and DNA fragmentation study and assessed drug-DNA interaction by comparative analysis of circular dichroism (CD) spectral data and melting temperature profiles (T(m)) of calf thymus DNA treated with or without EESJ. We observed an elevation of all biomarkers for oxidative stress, generation of ROS and activation of NFkB and down regulation in expression of insulin, GLUT2 and glucokinase in hyperglycemic mice. Administration of EESJ reversed these changes. Histo-pathological observations of pancreas, liver and kidney also revealed relevant changes. Data of CD and (T(m)) indicated an interaction of EESJ with calf thymus DNA, indicating change in structure and conformation. Thus, EESJ has anti-oxidant as well as anti-hyperglycemic activities in diabetic mice, and potentially useful in management of hyperglycemia.
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741 235, India.
authors.forename: Asmita
authors.initials: A
authors.lastname: Samadder
authors.forename: Debrup
authors.initials: D
authors.lastname: Chakraborty
authors.forename: Arnab
authors.initials: A
authors.lastname: De
authors.forename: Soumya Sundar
authors.initials: SS
authors.lastname: Bhattacharyya
authors.forename: Kakali
authors.initials: K
authors.lastname: Bhadra
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
mesh_terms: D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001713:Biphenyl Compounds / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D020552:Comet Assay; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010851:Picrates / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D027842:Syzygium / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D005609:Free Radicals; D007004:Hypoglycemic Agents; D010851:Picrates; D010936:Plant Extracts; D000431:Ethanol; D000496:Alloxan; D004247:DNA; C427203:calf thymus DNA; C004931:1,1-diphenyl-2-picrylhydrazyl