Delhi Institute of Pharmaceutical science and Research

Delhi, India

Delhi Institute of Pharmaceutical science and Research

Delhi, India
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Sharma N.,Delhi Institute of Pharmaceutical science and Research | Pathak D.P.,Delhi Institute of Pharmaceutical science and Research
International Journal of Pharmacy and Pharmaceutical Sciences | Year: 2016

Cancer claims the second largest number of deaths across the globe every year. With the new addition and discoveries in the therapeutic area, there are also some serious challenges which come into play. These include the emergence of resistance, malignancy, relapses and some life-threatening adverse effects. These challenges further intensify the need to discover better alternatives. Thiosemicarbazones have been explored extensively against many resistant and non-resistant forms of cancer in vitro as well as in vivo. Chelation of iron and copper has been attributed to their activity as anticancer agents, but recent studies have revealed few more complex mechanisms of their action. With different approaches to target different aspects of cancers, they have gained ample attention. Structural variations of these compounds were found to be highly selective in their action. © 2016 The Authors.


Gandhi S.,Delhi Institute of Pharmaceutical science and Research | Srinivasan B.P.,Delhi Institute of Pharmaceutical science and Research | Akarte A.S.,Delhi Institute of Pharmaceutical science and Research
European Journal of Pharmaceutical Sciences | Year: 2012

The present study aims to investigate the combined and individual treatment of aliskiren and olmesartan for 8 weeks in streptozotocin induced diabetic rats provide an effective blockade of RAAS by improving glucose homeostasis, glomerular filtration rate along with renal variables thereby delaying the progression of the disease. Streptozotocin induced diabetic rats were administered with aliskiren (10 mg/kg/day), olmesartan (6 mg/kg/day) alone and in combination. To identify the glucose homeostasis, translocation of glucose transporter proteins in liver and muscle was observed by their expression after treatment. Glomerular filtration rate is estimated using serum creatinine, cystatin C and beta 2 microglobulin. This study also examined the effects of combination and monotherapy on various renal variables viz. albumin, total proteins, TGF-β, TNF-α, VEGF, nitric oxide, adiponectin and erythropoeitin. In addition, histopathological and anti-apoptotic profile of kidney was also investigated. The present study indicates that dual blockade of RAAS improved glucose homeostasis and confirms the nephroprotective effects of the combined treatment of aliskiren and olmesartan independent of their antihypertensive property in the STZ induced diabetes. In addition, its antifibrotic, antiproteinuric effects indicate that combination treatment might be potential as an important therapeutic option for chronic fibrotic diseases in renal complications. © 2012 Elsevier B.V. All rights reserved.


Agrawal S.S.,Amity University | Naqvi S.,Delhi Institute of Pharmaceutical science and Research | Gupta S.K.,Delhi Institute of Pharmaceutical science and Research | Srivastava S.,Delhi Institute of Pharmaceutical science and Research
Food and Chemical Toxicology | Year: 2012

We investigated the potential of Tinospora cordifolia (TC) in treatment of diabetic retinopathy in STZ-induced rats due to its antihyperglycemic, angiogenic, antiinflammatory and antioxidant effects. The diabetic rats, treated for 24. weeks with TC extract (250. mg/kg), were evaluated for lenticular and fundus changes. Biochemical parameters were estimated and histopathological studies performed. TC significantly reduced blood glucose and glycated hemoglobin in treated rats. It prevented cataract development in treated group. Angiogenic markers VEGF and PKC increased in diabetic retina, which reduced significantly with TC. Anti-inflammatory parameters TNF-α and IL-1β elevated in diabetic group unlike that in treated group. TC also provided defense against depletion of antioxidant enzymes- glutathione and catalase. Histopathological studies revealed thickening of basement membrane of the retinal and glomerular vasculature of diabetic rat, but no basement membrane widening was seen in treated animals. Destruction of pancreatic islet structure was observed in diabetic group, but not in treated. Thus, TC reduces blood glucose and inhibits overexpression of angiogenic and inflammatory mediators, which are distinct markers of diabetic retinopathy. It also prevents retinal oxidative stress and restores antioxidant enzyme levels. These data provide evidence for the safety and potential effect of TC in the management of experimental diabetic retinopathy. © 2012 Elsevier Ltd.


Saraswati S.,Delhi Institute of Pharmaceutical science and Research | Agrawal S.S.,Amity University
Cancer Letters | Year: 2013

In this study, we investigated the mechanism of brucine in tumor angiogenesis. We found that brucine inhibits VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures in HUVECs in a dose-dependent manner. Brucine suppresses VEGF- induced p-VEGFR2 kinase activity and inhibits neovascularization in vivo. Brucine inhibits the downstream protein kinases of VEGFR2, including Src, FAK, ERK, AKT and mTOR. And further downregulates levels of VEGF, NO, IL-6, IL-8, TNF-α and IFN-γ in HUVECs. Taken together, our study suggests that brucine potently suppresses angiogenesis by targeting VEGFR2 activation and may be a viable drug candidate in anti-angiogenesis and anti-cancer therapies. © 2013 Elsevier Ireland Ltd.


Saraswati S.,Delhi Institute of Pharmaceutical science and Research | Agarwal S.S.,Amity University
Microvascular Research | Year: 2013

Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5. mg/kg/day) was given through installed cannulas for 9. days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour Necrosis Factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine. © 2013 Elsevier Inc.


Akarte A.S.,Delhi Institute of Pharmaceutical science and Research | Srinivasan B.P.,Delhi Institute of Pharmaceutical science and Research | Gandhi S.,Delhi Institute of Pharmaceutical science and Research
Journal of Diabetes and its Complications | Year: 2012

Objective: Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic β-cell mass and function due to oxidative stress induced inflammation. Here, we investigated the effects of a potent and selective DPP-4 inhibitor vildagliptin on glycemic control, pancreatic β-cell mass and function, genes and proteins expressions, tumor necrosis factor-alpha, and nitric oxide in an n2-STZ diabetic model of rat with defects in insulin sensitivity and secretion. Method: To induce NIDDM, STZ (sigma chemicals, USA) (90 mg/kg) was administered i.p. to a group of 2 days old pups. Another group of pups received only saline. The pups were weaned for 21 days, and 6 weeks after the injection of STZ, the animals were checked for fasting glucose level (FPG) ≥ 160 mg/dl were considered as diabetic. Results: Significant and dose-dependent correction of postprandial and fasting hyperglycemia was observed in diabetic rats following 8 weeks of chronic therapy. Treatment with vildagliptin showed increase in the number of insulin-positive β-cells in islets and improved the expressions of genes and proteins are responsible for insulin secretions. In addition, treatment of rats with vildagliptin significantly increased insulin content; and decreased the nitric oxide and TNF-alpha concentration. Conclusion: These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of diabetes mellitus by modifying the courses of the disease. © 2012 Elsevier Inc. All rights reserved.


Agrawal S.S.,Delhi Institute of Pharmaceutical science and Research | Saraswati S.,Delhi Institute of Pharmaceutical science and Research | Mathur R.,Delhi Institute of Pharmaceutical science and Research | Pandey M.,Delhi Institute of Pharmaceutical science and Research
Life Sciences | Year: 2011

Aims: Brucine (BRU), a natural plant alkaloid is reported to possess cytotoxic and antiproliferative activities. In this study we aimed to investigate its in vitro and in vivo antitumor and antiangiogenic effects. Main methods: Cell proliferation and viability was assessed using microculture tetrazolium tests (MTT). As predictive markers we determined intracellular levels of vascular endothelial growth factor (VEGF), Interleukin-12 (IL-12), tumor necrosis factor (TNF-α), caspase-3, -8 and -9 by ELISA and enzymatic activity assays. In addition, anti-VEGF neutralization effect was evaluated to assess whether it could result in augmented anticancer efficacy than the single agent. Antitumor activity was evaluated against Ehrlich ascites and solid tumor models. 15×106 EAC cells were implanted intraperitoneally (i.p., ascites tumor) and subcutaneous (s.c., solid tumor) in Swiss albino mice. Mice with established tumors received brucine i.p. at 12.5, 25, and 50 mg/kg for 14 days in ascites tumor and 50 mg/kg in solid tumor for 30 days. Tumor volume, cell viability, angiogenic, anti-angiogenic, anti-inflammatory factors and antioxidant parameters were determined. Immunohistochemistry analysis for VEGF and CD-31 was also performed. Key findings: BRU produced time and dose-dependent inhibition of MCF-7 in vitro and EAC tumors in vivo. The anti-angiogenic effects were accompanied with decreased VEGF and TNF-α and increased IL-12 expression. BRU reduced peritoneal angiogenesis and microvessel density in vivo. Conclusion: Our findings suggest that BRU possesses antitumor and anti-angiogenic activities in vitro and in vivo. The above results showed that BRU can be used as a potential anticancer agent as an antimetastatic and anti-angiogenic agent. © 2011 Elsevier Inc. All rights reserved.


Agrawal S.S.,Delhi Institute of Pharmaceutical science and Research | Saraswati S.,Delhi Institute of Pharmaceutical science and Research | Mathur R.,Delhi Institute of Pharmaceutical science and Research | Pandey M.,Delhi Institute of Pharmaceutical science and Research
Food and Chemical Toxicology | Year: 2011

Boswellic acid (BA), a triterpene, isolated from Boswellia serrata (Burseraceae) has been found to possess potent anti-inflammatory and anti-cancer activity. The present study aimed at exploring the possible role of BA on ascites and solid Ehrlich tumor. Ascitic tumor development was evaluated 14. d after tumor implantation by quantification of the ascitic fluid volume whereas solid tumor was evaluated after 30. d tumor implantation by H&E and IHC. The i.p. administration of BA significantly inhibited ascitic and solid Ehrlich tumor model. This inhibition was observed with reduced ascitic volume, solid tumor volume and body weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. VEGF and TNF- α levels were decreased, whereas the IL-12 levels were increased with BA treatment at 25. mg/kg. Further, results on decrease in the peritoneal angiogenesis and microvessel density showed the anti-angiogenic potential. Microscopic examination of tumors revealed that in BA-treated groups the expression of Bax and caspase 3 increased, suggesting drug induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3. The present study sheds light on the potent antitumor property of the boswellic acid and can be extended further to develop therapeutic protocols for treatment of cancer. © 2011 Elsevier Ltd.


Patent
Delhi Institute Of Pharmaceutical Science And Research | Date: 2013-10-03

The present invention relates to the use of garcinol as a nephroprotective agent. The present invention also relates to the use of garcinol as a therapeutic agent in renal disorders, in particular diabetic nephropathy, and to medicinal preparations containing garcinol. Further disclosed herein are method of treatment of renal disorders, in particular diabetic nephropathy by administration of garcinol.


Gandhi S.,Delhi Institute of Pharmaceutical science and Research | Srinivasan B.P.,Delhi Institute of Pharmaceutical science and Research | Akarte A.S.,Delhi Institute of Pharmaceutical science and Research
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2013

Aliskiren, a direct renin inhibitor (DRI), has therapeutic effects in patients with hypertension and associated complications, but its potential mechanism in diabetic nephropathy is lacking. The effects of aliskiren in Streptozotocin (STZ)-induced renal complication in diabetic rats were investigated. Aliskiren treatment for eight weeks at the dose of 10 mg/kg/day, via osmotic mini-pump, induced improvement in blood glucose levels, systolic blood pressure (BP) and serum creatinine. Improvement of insulin resistance by aliskiren was confirmed by increased glucose translocation in liver and muscle and hence insulin levels. The treated group also showed improvement in glomerulosclerosis and tubulointerstitial injury. Aliskiren treatment also improved albumin levels in plasma, suppressed profibrotic and proinflammatory cytokine synthesis viz TNF-α and TGF-β and angiogenesis by a decrease in VEGF. In addition, the level of total proteins and GFR via cystatin c and beta-2microglobulin along with adiponectin and erythropoietin were also improved. These results suggest that the beneficial organ protective effect of aliskiren is mediated by improvement in insulin resistance as well as a direct anti-fibrotic effect in the target organ in STZ-induced diabetic rats with a slight effect on blood pressure. Aliskiren may be a useful therapeutic agent in the treatment of type 2 diabetes and diabetic nephropathy. © 2012 The Author(s).

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