Dharamvir Singh Arya

AIIMS Bhopal All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India

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Publications (84)176.87 Total impact

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    ABSTRACT: Myocardial infarction (MI) is an insidious disease, gently spreading in developed and developing countries. MI is the consequence of hypoxia in myocardial tissue, which may lead to apoptosis, narcosis and followed by cardiac cell death. Activation of apoptotic pathways during MI is frequently reported in clinical, preclinical and post-mortem studies. Several mediators of apoptosis signalling cascades culminate into MI leading to cardiomyocytes death. Such involvements of ischemia-induced apoptosis in MI are widely accepted. Apoptosis is a natural phenomenon for regulating the homeostasis in cellular organelles. Unlike the necrosis, it is a synchronized energy dependent process which is carried out by shrinkage of the cell. This contraction of cells leads to squeezing of nuclei and nuclear chromatin into brusquely demarcated masses. However, such programmed cell death in several tissues, including the myocardium becomes pathogenic under certain conditions. Moreover, reactive oxygen species (ROS) generated oxidative stress also plays a key role in production of apoptosis and several associated signalling alterations which ultimately lead to MI. Recently, certain natural products, especially from the plant kingdom have been evaluated for their anti-apoptotic potential. There is an uprise in the investigations delineating the exact mechanisms through which natural phytochemicals target apoptosis associated MI. This review explores novel signalling pathways and target sites for anti-apoptotic phytochemicals having potential to check the cellular apoptosis consequent to MI. A new vista may explore the prospective treatment of MI by using apoptosis-modulating natural products.
    Cardiovascular & hematological agents in medicinal chemistry. 01/2015;
  • Saurabh Bharti, Neha Rani, Jagriti Bhatia, Dharamvir Singh Arya
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    ABSTRACT: Recent studies have proposed the potential role of 5-HT2B receptor (5-HT2BR) blockade in alleviating myocardial dysfunction; hitherto, the regulatory pathway for its protective effect has remained enigmatic. In the present study, we sought to investigate the role of SB-204741, a 5-HT2BR blocker in isoproterenol-induced myocardial remodeling in rats and its cross-talk with apoptosis and mitogen activated protein kinase (MAPKs)/heat shock proteins (HSPs) pathway. To assess this hypothesis, we measured the effect of SB-204741 (0.25-1.0 mg/kg/day, i.p.) in isoproterenol (85 mg/kg/day, s.c.)-induced myocardial remodeling in rats. SB-204741 dose dependently improved hemodynamic and ventricular functions following isoproterenol-induced myocardial injury. This amelioration was well substantiated with reduced expression of 5-HT2B, inflammatory proteins (NF-κBp65, IKK-β, TNF-α, IL-6, and Cox-2), MAPKs (p-p38/p38 and p-JNK/JNK ratio) accompanied with increased protein expression of HSPs (αB-crystallin, Hsp27 and Hsp70), autophagy (LC3 and Beclin-1) and p-ERK/ERK ratio. Additionally, SB-204741 inhibited apoptotic signaling pathway as there was decreased DAPI/TUNEL positivity and protein expression of cytochrome c, Bax, and caspase-3 along with increased Bcl-2 expression. Preservation of histopathological and ultrastructural components, normalization of nitric oxide level, endogenous antioxidants and myocyte injury marker enzymes were also observed. In conclusion, inhibition of apoptosis via modulation of MAPKs/HSPs is essential for 5-HT2BR blockade mediated cardioprotective effect.
    APOPTOSIS 12/2014; · 3.61 Impact Factor
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    ABSTRACT: Nephrotoxicity is a major adverse effect of the widely used anticancer drug cisplatin. Oxidative stress, inflammation and apoptosis are implicated in the pathophysiology of cisplatin-induced acute renal injury. Moreover, cisplatin activates many signal transduction pathways involved in cell injury and death, particularly mitogen activated protein kinase (MAPK) pathway. With this background, we aimed to investigate the protective effect of telmisartan, a widely used antihypertensive drug, in cisplatin-induced nephrotoxicity model in rats. To accomplish this, male albino wistar rats (150-200g) were divided into 6 groups: Normal, cisplatin-control, telmisartan (2.5, 5 and 10mg/kg) and telmisartan per se treatment groups. Normal saline or telmisartan was administered orally to rats for 10 days and cisplatin was given on 7(th) day (8mg/kg; i.p.) to induce nephrotoxicity. On 10(th) day, rats were killed and both the kidneys were harvested for biochemical, histopathological and molecular studies. Cisplatin injected rats showed depressed renal function, altered proxidant-antioxidant balance and acute tubular necrosis which was significantly normalized by telmisartan co-treatment. Furthermore, cisplatin administration activated MAPK pathway that caused tubular inflammation and apoptosis in rats. Telmisartan treatment significantly prevented MAPK mediated inflammation and apoptosis. Among the three doses studied telmisartan at 10mg/kg dose showed maximum nephroprotective effect which could be due to maintenance of cellular redox status and inhibition of MAPK activation. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 12/2014; 748. · 2.68 Impact Factor
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    ABSTRACT: Impaired glucose metabolism either in prediabetes or diabetes mellitus is one of the detrimental root causes of premature mortality throughout the world. Uncontrolled prediabetes coincides with the induction of diabetic mellitus and associated cardiovascular diseases (CVDs). Needless to mention, impaired glucose metabolism, including impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), have been known individually or in combination as the prediabetic stage but by itself it is not diabetes mellitus. Impaired β-cell function, insulin resistance, increased level of free fatty acids, hyperinsulinemia and down-regulation of GLUT-4 are critical impairments during prediabetes. The vascular endothelium sustains the free flow of blood in vessels by normalizing vascular tone by releasing numerous endothelial-derived factors. However, in recent studies a marked impairment in endothelial-derived factors has been observed in prediabetes. Thus, the impaired endothelial-derived factors could make prediabetic patients more vulnerable to cardiovascular disease pathology. Nobel laureates, Robert Furchgott, Louis Ignarro and Ferid Murad (1998) discovered a novel signalling molecule, nitric oxide (NO), identified as an endothelium-derived relaxing factor. This imperative mediator has potent vasodilatory, anti-platelet, anti-proliferative, and anti-inflammatory actions in vessels. Endothelium-derived NO generation is mediated through the activation of PI3-K-Akt-eNOS-NO signalling pathways. Therefore, conspicuous destruction in PI3-K-Akt-eNOS-NO signalling has been revealed in prediabetes and renders individuals more susceptible to CVDs. Several research reports have defined prediabetes as a platform for diabetes mellitus and associated CVDs. But the molecular alteration during prediabetes is unclear; however, the signalling modulator may be an imperative issue and may open a prerequisite new vista for novel research. In this review, we have critically discussed the possible signalling alteration in prediabetes.
    RSC Advances 11/2014; 5(2):1619. · 3.71 Impact Factor
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    ABSTRACT: The present study investigated the effect of hesperidin, a natural flavonoid, in cardiac ischemia and reperfusion (I/R) injury in diabetic rats. Male Wistar rats with diabetes were divided into five groups and were orally administered saline once daily (IR-sham and IR-control), Hesperidin (100 mg/kg/day; IR-Hesperidin), GW9962 (PPAR-γ receptor antagonist), or combination of both for 14 days. On the 15th day, in the IR-control and IR-treatment groups, rats were subjected to left anterior descending (LAD) coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical, histopathological, ultrastructural and immunohistochemistry. In the IR-control group, significant ventricular dysfunctions were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in cardiac injury markers lactate dehydrogenase activity, CK-MB and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and TNF-α were observed. Hesperidin pretreatment significantly improved mean arterial pressure, reduced left ventricular end-diastolic pressure, and improved both inotropic and lusitropic function of the heart (+LVdP/dt and -LVdP/dt) as compared to IR-control. Furthermore, hesperidin treatment significantly decreased the level of thiobarbituric acid reactive substances and reversed the activity of lactate dehydrogenase towards normal value. Hesperidin showed anti-apoptotic effects by upregulating Bcl-2 protein and decreasing Bax protein expression. Additionally, histopathological and ultrastructural studies reconfirmed the protective action of hesperidin. On the other hand, GW9662, selective PPAR-γ receptor antagonist, produced opposite effects and attenuated the hesperidin induced improvements. The study for the first time evidence the involvement of PPAR-γ pathway in the cardioprotective activity of hesperidin in I/R model in rats.
    PLoS ONE 11/2014; 9(11):e111212. · 3.53 Impact Factor
  • S Bharti, N Rani, D S Arya
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    ABSTRACT: Purpose: We established previously that Crocus sativus and its carotenoid crocin protects the myocardium via augmenting the endogenous antioxidant defense system. Since, heat shock protein70 (Hsp70) actively participates in shielding the cell from oxidative stress, programmed or necrotic cell deaths; we hypothesized that Hsp70 might be the actual mediator behind the cardioprotective effects of crocin. Methods: To document this interplay between crocin and Hsp70, we administered crocin (20mg/kg/day, p.o.) and Hsp70 inhibitor, KNK437 (25mg/kg/day, i.p.) for 14 days followed by left anterior descending coronary artery ligation for 45 minutes and reperfusion for 60 minutes on the 15th day. Results: Intriguingly, crocin pretreatment significantly ameliorated (P<0.05) hemodynamic status, myocardial architecture and decreased infarct size in ischemia-reperfusion challenged myocardium. This improvement in functional and morphological changes were corroborated with suppression of inflammatory (IKK-beta/NF-kappaB and TNF-alpha), apoptotic (TUNEL positivity and Bax expression) and cardiac injury markers (CK-MB, LDH and BNP), along with upregulation of Hsp70 protein expression. In addition, crocin bolstered the antioxidant defense system as manifested by augmented activities of GSH, GSHPx and overexpression of MnSOD protein expression levels. Surprisingly, co-treatment with KNK437 abrogated the crocin-induced cardioprotection with significant amplification in infarct size, inflammation, apoptosis and oxidative stress markers. Conclusion: For the first time, present study unravels that crocin attenuates ischemia-reperfusion injury through augmenting Hsp70 expression and could be developed as a nutriment for alleviating acute myocardial infarction.
    Cardiovascular Research 07/2014; 103(suppl 1):S24. · 5.81 Impact Factor
  • N Rani, S Bharti, D S Arya
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    ABSTRACT: Chrysin (5,7-dihydroxylflavone), an agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to possess antioxidant and anti-inflammatory properties. Here, we investigated whether chrysin (60 mg/kg/day) can improve the pathophysiology of myocardial infarction in diabetes partially through the PPAR-gamma pathway by assessing a variety of indices, e.g., hemodynamic, biochemical, histoarchitectural changes, and apoptosis.
    Cardiovascular Research 07/2014; 103(suppl 1):S81. · 5.81 Impact Factor
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    ABSTRACT: Purpose: Seabuckthorn pulp oil obtained from the fruits of Seabuckthorn (Hippophae rhamnoides L.) has been used since ancient times for its medicinal and nutritional properties. So the present study was done to investigate the cardioprotective effect of Seabuckthorn (SBT) pulp oil in Ischemia-Reperfusion (IR) induced model of myocardial infarction in rats and to evaluate whether this cardioprotective effect involves activation of Akt/eNOS signaling pathway. Methods: Male albino Wistar rats were divided into three groups: 1-Sham; 2-IR control; 3-SBT pulp oil (20 ml/kg/day; p.o.). SBT pulp oil or vehicle was administered for 30 days. On 31st day, animals underwent left anterior descending coronary artery ligation for 45 min and reperfusion for 60 min. Results: As compared to sham group, IR injury showed cardiac dysfunction as demonstrated by lowering of mean arterial blood pressure, decrease in maximum positive and negative rate of left ventricular pressure (±LVdP/dtmax) and an increase in left ventricular end-diastolic pressure (LVEDP). Furthermore, there was marked rise in lipid peroxidation, increase in cardiac injury enzyme activities in serum, depletion of antioxidant status along with increase in serum TNF-α and decrease in NO levels. Histopathological study revealed focal necrosis, edema and infiltration of inflammatory cells. Pretreatment with SBT pulp oil (20 ml/kg/day; p.o.) significantly prevented the cardiac necroenzyme release, decreased inflammation, improved cardiac function, restored myocardial oxidant-antioxidant status and decreased the TNF-α level in the serum. Furthermore, it downregulated the IKKβ/NF-κB expression and increased the Akt-eNOS phosphorylation in IR challenged myocardium. Conclusion: Thus we conclude that SBT pulp oil shields the myocardium against IR injury via modulation of Akt-eNOS and IKKβ/NF-κB expression. View this table:View popupView inline
    Cardiovascular Research 07/2014; 103(suppl 1):S118-S119. · 5.81 Impact Factor
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    ABSTRACT: Hesperidin has been shown to possess cardioprotective and anti-diabetic potential. Hitherto, its molecular mechanism on isoproterenol (ISO)-induced myocardial dysfunction in diabetes is still not explored. Hence, for the first time we sought to investigate whether hesperidin exerts any beneficial effect on the pathophysiology of myocardial infarction (MI) in diabetes through the PPAR-γ pathway by assessing a variety of indices e.g., apoptosis, hemodynamic, biochemical and histoarchitectural changes. Diabetes was induced by a single dose of STZ (50 mg/kg IP). Diabetic rats received either hesperidin (100 mg/kg/day orally), the PPAR-γ antagonist GW9662 (1 mg/kg/day IP), or both for 14 days with concurrent administration of ISO (85 mg/kg SC) on days 13 and 14. ISO-STZ rats resulted in severe myocardial dysfunction (decreased ±LVdP/dt and increased LVEDP). In addition, augmented myocardial thiobarbituric acid-reactive substances and serum troponin-I with a concomitant decrease in level of glutathione and activities of catalase, superoxide dismutase antioxidants with cardiac injury biomarkers creatine kinase-MB isoenzyme, lactate dehydrogenase were seen. Morphological studies of the ISO-STZ challenged myocardium exhibited severe necrosis, edema and inflammatory changes. In western blot analysis, Bcl-2 and PPAR-γ expression were decreased where as Bax expression was significantly increased, suggesting role of apoptosis in myocardial dysfunction. Interestingly, hesperidin treatment positively modulated these parameters as validated by improved hemodynamic and left ventricular functions, fortified endogenous anti-oxidant defence system and improved structural integrity of the myocardium. However, significant effects were lowered in animals treated with hesperidin plus GW9662. Moreover, down-regulated PPAR-γ and Bcl-2 expressions in myocardial infarcted diabetic hearts were increased by hesperidin treatment. Hence, for the first time the present study suggests that, hesperidin reduces oxidative stress, apoptosis and improves cardiac function via the PPAR-γ pathway.
    Chemico-Biological Interactions 06/2014; · 2.98 Impact Factor
  • Jagriti Bhatia, Nanda Gamad, Saurabh Bharti, Dharamvir Singh Arya
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    ABSTRACT: Canagliflozin (CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter (SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus.
    World journal of diabetes. 06/2014; 5(3):399-406.
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    ABSTRACT: Naringin, chemically 4',5,7- trihydroxyflavanone-7-rhamnoglucoside, is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It has been experimentally documented to possess numerous biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. In vitro and in vivo studies have further established the usefulness of naringin in various preclinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders. Apart from this, naringin has also exerted chemopreventive and anticancer attributes in various models of oral, breast, colon, liver, lung, and ovarian cancer. This wide spectrum of biological expediency has been documented to be a result of either the upregulation of various cell survival proteins or the inhibition of inflammatory processes, or a combination of both. Due to the scarcity of human studies on naringin, this review focuses on the various established activities of naringin in in vitro and in vivo preclinical models, and its potential therapeutic applications using the available knowledge in the literature. Additionally, it also encompasses the pharmacokinetic properties of naringin and its inhibition of CYP isoenzymes, and the subsequent drug interactions. Moreover, further clinical research is evidently needed to provide significant insights into the mechanisms underlying the effects of naringin in humans.
    Planta Medica 04/2014; · 2.35 Impact Factor
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    ABSTRACT: Naringin has antioxidant properties that could improve redox-sensitive myocardial ischemia reperfusion (IR) injury. This study was designed to investigate whether naringin restores the myocardial damage and dysfunction in vivo after IR and the mechanisms underlying its cardioprotective effects. Naringin (20-80 mg/kg/day, p.o.) or saline were administered to rats for 14 days and the myocardial IR injury was induced on 15(th) day by occluding the left anterior descending coronary artery for 45 min and subsequent reperfusion for 60 min. Post-IR rats exhibited pronounced cardiac dysfunction as evidenced by significantly decreased mean arterial pressure, heart rate, +LVdP/dt max (inotropic state), -LVdP/dt max (lusitropic state) and increased left ventricular end diastolic pressure as compared to sham group, which was improved by naringin. Further, on histopathological and ultrastructural assessments myocardium and myocytes appeared more normal in structure and the infarct size was reduced significantly in naringin 40 and 80 mg/kg/day group. This amelioration of post-IR-associated cardiac injury by naringin was accompanied by increased nitric oxide (NO) bioavailability, decreased NO inactivation to nitrotyrosine, amplified protein expressions of Hsp27, Hsp70, β-catenin and increased p-eNOS/eNOS, p-Akt/Akt, and p-ERK/ERK ratio. In addition, IR-induced TNF-α/IKK-β/NF-κB upregulation and JNK phosphorylation were significantly attenuated by naringin. Moreover, western blotting and immunohistochemistry analysis of apoptotic signaling pathway further established naringin cardioprotective potential as it upregulated Bcl-2 expression and downregulated Bax and Caspase-3 expression with reduced TUNEL positivity. Naringin also normalized the cardiac injury markers (lactate dehydrogenase and creatine kinase-MB), endogenous antioxidant activities (superoxide dismutase, reduced glutathione and glutathione peroxidase) and lipid peroxidation levels. Thus, naringin restored IR injury by preserving myocardial structural integrity and regulating Hsp27, Hsp70, p-eNOS/p-Akt/p-ERK signaling and inflammatory response.
    PLoS ONE 12/2013; 8(12):e82577. · 3.53 Impact Factor
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    ABSTRACT: Normal rats pre-treated with P. kurroa (200 mg/kg) alone did not showed significant change, however, isoproterenol (ISP) administration resulted in hemodynamic and left ventricular dysfunction, oxidative stress, and lipid peroxidation. Such cardiac dysfunction was significantly prevented by P. kurroa root extract pre-treatment. Pre-treatment significantly attenuated the ISP-induced oxidative stress by restoring myocardial superoxide dismutase, catalase, and glutathione peroxidase enzymes except reduced glutathione content. P. kurroa pre-treatment markedly attenuated the ISP-induced rise in lipid peroxidation, thereby prevented leakage of myocyte creatine kinase-MB and lactate dehydrogenase enzymes. The results suggest that P. kurroa root extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, anti-peroxidative, and myocardial preservative properties.
    Indian journal of experimental biology 09/2013; 51(9):694-701. · 0.75 Impact Factor
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    ABSTRACT: The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.
    Toxicology and Industrial Health 06/2013; · 1.71 Impact Factor
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    ABSTRACT: The present study was undertaken to scientifically evaluate, validate and compare the cardioprotective effects of lisinopril (Lsp), an angiotensin converting enzyme (ACE) inhibitor and vitamin E (Vit E), an antioxidant in the setting of ischemia and reperfusion (I-R) injury. An open chest left anterior descending coronary artery occlusion and reperfusion induced myocardial injury cardiotoxicity model was used in the present study. Hemodynamic, biochemical and histopathological assessment of myocardial injury was undertaken. Pre-treatment (1 month) with Lsp (50mg/kg) and Vit E (100mg/kg) to healthy experimental controls did not adversely affect the histopathological architecture of the myocardium as well as the baseline antioxidant parameters. Subsequent to I-R injury, Lsp demonstrated modest antioxidant effects, superior recovery in left ventricular function as compared to the control IR group. Histopathological and biochemical assessment of injury confirmed the myocardial salvaging effect of this intervention. The cardioprotection afforded by Lsp was found to be superior as compared to Vit E treatment.
    Environmental toxicology and pharmacology. 12/2012; 35(2):207-217.
  • Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 11/2012; · 1.43 Impact Factor
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    ABSTRACT: Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption.
    Biochemical pharmacology 07/2012; 84(7):974-83. · 4.25 Impact Factor
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    ABSTRACT: Syzygium cumini (SC) is well known for its anti-diabetic potential, but the mechanism underlying its amelioration of type 2 diabetes is still elusive. Therefore, for the first time, we investigated whether SC aqueous seed extract (100, 200, or 400 mg/kg) exerts any beneficial effects on insulin resistance (IR), serum lipid profile, antioxidant status, and/or pancreatic β-cell damage in high-fat diet / streptozotocin-induced (HFD-STZ) diabetic rats. Wistar albino rats were fed with HFD (55% of calories as fat) during the experiment to induce IR and on the 10th day were injected with STZ (40 mg/kg, i.p.) to develop type 2 diabetes. Subsequently, after confirmation of hyperglycemia on the 14th day (fasting glucose level > 13.89 mM), diabetic rats were treated with SC for the next 21 days. Diabetic rats showed increased serum glucose, insulin, IR, TNF-α, dyslipidemia, and pancreatic thiobarbituric acid-reactive substances with a concomitant decrease in β-cell function and pancreatic superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzyme activities. Microscopic examination of their pancreas revealed pathological changes in islets and β-cells. These alterations reverted to near-normal levels after treatment with SC at 400 mg/kg. Moreover, hepatic tissue demonstrated increased PPARγ and PPARα protein expressions. Thus, our study demonstrated the beneficial effect of SC seed extract on IR and β-cell dysfunction in HFD-STZ-induced type 2 diabetic rats.
    Journal of Pharmacological Sciences 06/2012; 119(3):205-13. · 2.11 Impact Factor
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    FEBS Letters 06/2012; 586(13):1832. · 3.34 Impact Factor

Publication Stats

635 Citations
176.87 Total Impact Points


  • 2014
    • AIIMS Bhopal All India Institute of Medical Sciences
      Bhopal, Madhya Pradesh, India
  • 2004–2014
    • All India Institute of Medical Sciences
      • Department of Pharmacology
      New Dilli, NCT, India
  • 2011
    • University of Delhi
      • Department Of Biomedical Science
      Delhi, NCT, India
  • 2009
    • Indian Agricultural Research Institute
      • Division of Plant Physiology
      New Dilli, NCT, India