Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response

Journal of Translational Medicine

Muhammad Zia-Ul-Haq¹  Vincenzo DeFeo²  Moumita Gangopadhyay⁴  Ranabir Sahu³  Tarun K Dua³  Saikat Dewanjee³  Ritu Khanra³ 

[1] Office of Research, Innovation and Commercialization, Lahore College for Women University, Lahore 54600, Pakistan;Department of Pharmacy, University of Salerno, Fisciano, Salerno 84084, Italy;Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India;Biophysics Division, Saha Institute of Nuclear Physics, Kolkata 700064, India

关键词: Type 2 diabetes mellitus;    Streptozotocin-nicotinamide;    Oxidative stress;    Nephropathy;    Cardiomyopathy;    Abroma augusta;   

Others  :  1146393
DOI  :  10.1186/s12967-014-0364-1

 received in 2014-10-08, accepted in 2014-12-16,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Khanra et al.; licensee BioMed Central.

【 图 表 】

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