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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. Source

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. Source

Rai B.K.,LNT College | Thakur A.,Amrita University | Divya,Delhi Institute of Pharmaceutical science and Research
Asian Journal of Chemistry | Year: 2013

A bidentate nitrogen/ oxygen containing Schiff base ligand, 3-amino-2-methyl quinazoline-4(3H)hydrazone (AMQH) and its Co(II), Ni(II) and Cu(II) complexes have been synthesized and characterized by molar mass, elemental analyses, spectral (IR and electronic) molar conductivity measurements at the room temperature. On the basis of above spectral and physicochemical studies it is proposed that ligand 3-amino-2-methyl quinazoline-4(3H)hydrazone acts in a bidentate manner and coordination proposes through amino group of quinazoline and azomethine N atom. The remaining coordination of metal ions are satisfied by negative ions such as Cl-, Br-, I- and NO3 -. The electronic spectral data proposes an octahedral geometry for Ni(II) and Co(II) while the geometry of Cu(II) complexes are proposed to be distorted octahedral in nature. Source

Saraswati S.,Delhi Institute of Pharmaceutical science and Research | Agrawal S.S.,Delhi Institute of Pharmaceutical science and Research
Biomedicine and Preventive Nutrition | Year: 2012

Boswellic acid possesses anticancer activity, however, its underlying mechanism(s) remain unexplored. Here, we report boswellic acid as a potent anticancer agent that acts against multiple intracellular targets that affect angiogenesis (VEGF), inflammation (TNF-α, IL-12), apoptosis (caspase-3 & -9) and antioxidant (SOD & CAT) based anticarcinogenic mechanisms. It inhibits MCF-7 cell proliferation and potentiates the cell death induced by VEGF antibody. A dose-dependent decrease in the levels of VEGF and TNF-α and significant increase in caspases-3 and -9 activities in MCF-7 cells were observed. To conclude, the results of the present study suggest that boswellic acts via multiple albeit specific molecular targets to elicit anticarcinogenic activity. © 2011 Elsevier Masson SAS. Source

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. Source

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