title: Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response.
abstract: BACKGROUND
  Abroma augusta L. (Malvaceae) leaf is traditionally used to treat diabetes in India and Southern Asia. Therefore, current study was performed to evaluate the protective effect of defatted methanol extract of A. augusta leaves (AA) against type 2 diabetes mellitus (T2DM) and its associated nephropathy and cardiomyopathy in experimental rats.
  
  
  METHODS
  Antidiabetic activity of AA extracts (100 and 200 mg/kg, p.o.) was measured in streptozotocin-nicotinamide induced type 2 diabetic (T2D) rat. Fasting blood glucose level (at specific interval) and serum biochemical markers (after sacrifice) were measured. Redox status, transcription levels of signal proteins (NF-κB and PKCs), mitochondria dependent apoptotic pathway (Bad, Bcl-2, caspase cascade) and histological studies were performed in kidneys and hearts of controls and AA treated diabetic rats.
  
  
  RESULTS
  Phytochemical screening of extracts revealed the presence of taraxerol, flavonoids and phenolic compounds in the AA. T2D rats showed significantly (p < 0.01) elevated fasting blood glucose level. Alteration in serum lipid profile and release of membrane bound enzymes like lactate dehydrogenase and creatine kinase, which ensured the participation of hyperlipidemia and cell membrane disintegration in diabetic pathophysiology. T2DM caused alteration in the serum biochemical markers related to diabetic complications. T2DM altered the redox status, decreased the intracellular NAD and ATP concentrations in renal and myocardial tissues of experimental rats. Investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation of NF-κB and increase in the concentrations of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in the renal and cardiac tissues. The activation of mitochondria dependent apoptotic pathway was observed in renal and myocardial tissues of the T2D rats. However, Oral administration of AA at the doses of 100 and 200 mg/kg body weight per day could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological studies also supported the protective characteristics of AA.
  
  
  CONCLUSIONS
  Results suggest that AA could offer prophylactic role against T2DM and its associated reno- and cardio- toxicity.
authors.affiliation: Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India. ritukhanra@yahoo.co.in.
authors.forename: Ritu
authors.initials: R
authors.lastname: Khanra
authors.affiliation: Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India. s.dewanjee@yahoo.com.
authors.forename: Saikat
authors.initials: S
authors.lastname: Dewanjee
authors.affiliation: Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India. tarunkduaju@gmail.com.
authors.forename: Tarun
authors.initials: T
authors.lastname: K Dua
authors.affiliation: Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India. ranaju4u@yahoo.co.in.
authors.forename: Ranabir
authors.initials: R
authors.lastname: Sahu
authors.affiliation: Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India. gangopadhyaymoumita75@gmail.com.
authors.forename: Moumita
authors.initials: M
authors.lastname: Gangopadhyay
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Salerno, 84084, Italy. defeo@unisa.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Feo
authors.affiliation: Office of Research, Innovation and Commercialization, Lahore College for Women University, Lahore, 54600, Pakistan. ahirzia@gmail.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zia-Ul-Haq
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D009202:Cardiomyopathies / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D019660:Malvaceae / Q000737:chemistry*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D064209:Phytochemicals / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry*; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D064209:Phytochemicals; D010936:Plant Extracts; D009243:NAD; D009536:Niacinamide; D000255:Adenosine Triphosphate