Evaluation of Methanolic Extract of Clitoria ternatea Hepatoprotective & Nephroprotective Activity in Rats

Objective: The aim of the study was to investigate the nephroprotective & hepatoprotective activity of methanolic extract of  Clitoria ternatea  in Cisplatin & CCl4 induced in rats Methods: Methanolic extract of aerial part of Clitoria ternatea  plant was studied  for its Nephroprotective  & Hepatoprotective activity in animal experiment models. Nephrotoxicity was induced by Cystone  16 mg/kg b.w . Standard drug was taken Silymarin .Test drug were given methanolic extract   Clitoria ternatea   500 mg/kg , 1000 mg/kg  . Hepatoxicity was induced by CCl4 .Standard drug was taken cisplatin 100 mg/kg . Test drugs were given extract of  Clitoria ternatea 500 mg/kg  & 1000 mg/kg as per b.w Results : In Hepatoprotective activity positive control group was provided with CCl4 and increased SGPT , SGOT , ALP level compare to negative control group whereas Test(2) group was  provided with methanolic extract of Clitoria ternatea  1000 mg/kg decreased SGPT , SGOT , ALP level compare to standard group. In nephroprotective activity positive control group was provided with CCl4 increased Urea and creatinine level where as Test(2) group are provided with methanolic extract of  Clitoria ternatea 1000 mg/kg decreased urea and creatinine level Conclusion: On evaluating biochemical parameters it was found that methanolic extract of Clitoria ternatea 1000 mg/kg showed hepatoprotective and nephroprotective activity in rats.   Keywords:  SGPT, SGOT, ALP, Nephroprotective, Hepatoprotective&nbsp

Studies on Magnetic and Dielectric Properties of Antiferromagnetically Coupled Dinuclear Cu(II) in a One-Dimensional Cu(II) Coordination Polymer

A one-dimensional Cu(II) coordination polymer with encapsulated antiferromagnetically coupled binuclear Cu(II) has been synthesized by using 5-nitroisophthalic acid (5-N-IPA) and 4-aminopyridine (4-APY) [Cu2(5-N-IPA)2(4-APY)4] n (1). Electrical properties are examined by complex impedance (Z*), dielectric permittivity (ε*), and ac conductivity studies at different frequencies (10 kHz-5 MHz) and temperatures (253-333 K). The contribution of grain and grain boundary has been explained by a different theoretical model. The variable temperature magnetic susceptibility data for compound 1 were recorded between 300 and 2 K. The shape of the curve (χM T vs T) indicates dominant antiferromagnetic coupling, which results from the interaction between the copper(II) atoms

An exhaustive overview of floating drug delivery system

The purpose of writing this review is to narrowing down on floating drug delivery systems (FDDS) and to compile the current literature with special focus on the principal mechanism of floatation to ameliorate gastric retention. The current amelioration of FDDS including the physiological and formulation variables affecting gastric retention approaches to design single unit and multiple unit floating systems, and a plethora and formulation aspects are covered in detail. This review also summarizes the in vitro technique and in vivo studies to evaluate the performance and application of floating systems and applications of these systems. These systems are useful to several plights encountered during the amelioration of a pharmaceutical dosage form. Keywords:  FDDS: Floating Drug Delivery System, ND: Narrowing down, PD: Pharmaceutical dosag

Putative Role of Ethanolic Extract of Vernonia cinerea in the Amelioration of Chemotherapy Induced Neuropathic Pain in Mice

Cancer chemotherapy is associated with a plethora of morbidities among which neuropathic pain is another one. The pathology underpinning chemotherapy induced neuropathic pain can be multifarious, however, dearth of effective medication largely plagues the quality of life of such patients. A good rationale can be found behind narrowing down on herbal alternatives namely methanolic extracts of Vernonia cinerea for which anti-cancer potential has already been reported. Hence we have carried out a pilot study for evaluating the protective potential of the methanolic extract of the plant against paclitaxel induced neuropathic pain in mice. Our evaluation has been based on standard paradigms focusing on neuromotor, oxidative and histopathological assessments and TNF α Assessment. We have found significant improvisation in groups treated with both pregabalin and extract, the amelioration being largely graded in nature. Hence our research has opened up the doors of a newer horizon of herbal alternatives available for chemotherapy induced neuropathic pain, however further look out into the domain is avidly awaited for. Keywords: NP: Neuropathic Pain, CC: Cancer Chemotherapy, HA: Herbal Alternative

Putative Role of Moringa oleifera in Prophylaxis of Chemotherapy Induced Neuropathic Pain in Mice

Cancer chemotherapy is associated with a plethora of morbidities among which neuropathic pain is a prevalent one. The pathology underpinning chemotherapy induced neuropathic pain can be multifarious, however, dearth of effective medication largely plagues the quality of life of such patients. A good rationale can be found behind focusing on herbal alternatives like extracts of Moringa oleifera for which anti-cancer potential has already been reported. Hence we have carried out a pilot study for evaluating the protective potential of the methanolic extract of the plant against paclitaxel induced neuropathic pain in mice. Our evaluation has been based on standard paradigms focusing on neuromotor, oxidative and histopathological assessments. We have found significant improvisation in groups treated with both pregabalin and extract, the amelioration being largely graded in nature. Hence our research has opened up the doors of a newer horizon of herbal alternatives available for chemotherapy induced neuropathic pain, however further look out into the domain is avidly awaited for. Keywords: NP: Neuropathic Pain, CC: Cancer Chemotherapy, HA: Herbal Alternative

Intracellular expression of IRF9 Stat fusion protein overcomes the defective Jak-Stat signaling and inhibits HCV RNA replication

Interferon alpha (IFN-α) binds to a cell surface receptor that activates the Jak-Stat signaling pathway. A critical component of this pathway is the translocation of interferon stimulated gene factor 3 (a complex of three proteins Stat1, Stat2 and IRF9) to the nucleus to activate antiviral genes. A stable sub-genomic replicon cell line resistant to IFN-α was developed in which the nuclear translocation of Stat1 and Stat2 proteins was prevented due to the lack of phosphorylation; whereas the nuclear translocation of IRF9 protein was not affected. In this study, we sought to overcome defective Jak-Stat signaling and to induce an antiviral state in the IFN-α resistant replicon cell line by developing a chimera IRF9 protein fused with the trans activating domain (TAD) of either a Stat1 (IRF9-S1C) or Stat2 (IRF9-S2C) protein. We show here that intracellular expression of fusion proteins using the plasmid constructs of either IRF9-S1C or IRF9-S2C, in the IFN-α resistant cells, resulted in an increase in Interferon Stimulated Response Element (ISRE) luciferase promoter activity and significantly induced HLA-1 surface expression. Moreover, we show that transient transfection of IRF9-S1C or IRF9-S2C plasmid constructs into IFN-α resistant replicon cells containing sub-genomic HCV1b and HCV2a viruses resulted in an inhibition of viral replication and viral protein expression independent of IFN-α treatment. The results of this study indicate that the recombinant fusion proteins of IRF9-S1C, IRF9-S2C alone, or in combination, have potent antiviral properties against the HCV in an IFN-α resistant cell line with a defective Jak-Stat signaling

Inflammatory Bowel Disease and Diabetes: An Association in Horizon

As we know inflammatory bowel disease is an emergent plight in rural and developing countries. In USA 10 million of peoples are suffering from IBD.IBD encompasses two pivotal kinds of pathological condition Ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiologically has a greater prevalence in the global prospective. So we decided to zero in on IBD in our work ahead. So a thorough search of available literature IBD is associated with plethora of comorbid disorders which includes gastrointestinal disorders arising from cholelithiasis, cutaneous disease like psoriasis, metabolic disorders like diabetes mellitus. Keywords:  IBD: inflammatory bowel disease, CD: Crohn’s disease, UC: Ulcerative colitis

Retropharmacology of Gliptins: A Focus on Inflammatory Bowel Disease

As we know inflammatory bowel disease is an emergent plight in developed & developing countries. IBD is an idiopathic ulceroinflammatory condition of the bowel which may or may not have transmural stretch. IBD has two clinic pathological condition Ulcerative colitis & Crohns’s disease. In United State of America there are 1.4 million of people suffering from Ulcerative colitis. IBD has a plethora of comorbid disorders .Gastrointestinal disorder arising from cholelithiasis, cutaneous disease arising from psoriasis & metabolic disorders arising from diabetes mellitus. DPP4 which is instrumental in aggravating diabetes mellitus gets hiked in IBD too , which may have serious implications in the worsening of the latter in diabetes . Hence, in our research we probed for the anticolitic potential of a standard inhibitor of DPP4, Linagliptin to ensure the enzymes suitability as a probable target for IBD. Keywords: IBD: Inflammatory Bowel Disease, UC: Ulcerative colitis, CD: Crohn’s diseas

Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in Huh-7 cells with a defective Jak-Stat pathway

<p>Abstract</p> <p>Background</p> <p>The sustained virological response to interferon-alpha (IFN-α) in individuals infected with hepatitis C virus (HCV) genotype 1 is only 50%, but is about 80% in patients infected with genotype 2-6 viruses. The molecular mechanisms explaining the differences in IFN-α responsiveness between HCV 1 and other genotypes have not been elucidated.</p> <p>Results</p> <p>Virus and host cellular factors contributing to IFN responsiveness were analyzed using a green fluorescence protein (GFP) based replication system of HCV 2a and Huh-7 cell clones that either possesses or lack a functional Jak-Stat pathway. The GFP gene was inserted into the C-terminal non-structural protein 5A of HCV 2a full-length and sub-genomic clones. Both HCV clones replicated to a high level in Huh-7 cells and could be visualized by either fluorescence microscopy or flow cytometric analysis. Huh-7 cells transfected with the GFP tagged HCV 2a genome produced infectious virus particles and the replication of fluorescence virus particles was demonstrated in naïve Huh-7.5 cells after infection. IFN-α effectively inhibited the replication of full-length as well as sub-genomic HCV 2a clones in Huh-7 cells with a functional Jak-Stat pathway. However, the antiviral effect of IFN-α against HCV 2a virus was not observed in Huh-7 cell clones with a defect in Jak-Stat signaling. HCV infection or replication did not alter IFN-α induced Stat phosphorylation or ISRE promoter-luciferase activity in both the sensitive and resistant Huh-7 cell clones.</p> <p>Conclusions</p> <p>The cellular Jak-Stat pathway is critical for a successful IFN-α antiviral response against HCV 2a. HCV infection or replication did not alter signaling by the Jak-Stat pathway. GFP labeled JFH1 2a replicon based stable cell lines with IFN sensitive and IFN resistant phenotypes can be used to develop new strategies to overcome IFN-resistance against hepatitis C.</p

Mechanism of HCV's resistance to IFN-α in cell culture involves expression of functional IFN-α receptor 1

The mechanisms underlying the Hepatitis C virus (HCV) resistance to interferon alpha (IFN-α) are not fully understood. We used IFN-α resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-α resistance in cell culture. The IFN-α resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-α receptor 1 (IFNAR1), IFN-α receptor 2 (IFNAR2), Jak1, Tyk2, Stat1, Stat2 and the ISRE- luciferase reporter plasmid. We demonstrated that the expression of the full-length IFNAR1 clone alone restored the defective Jak-Stat signaling as well as Stat1, Stat2 and Stat3 phosphorylation, nuclear translocation and antiviral response against HCV in all IFN-α resistant cell lines (R-15, R-17 and R-24) used in this study. Moreover RT-PCR, Southern blotting and DNA sequence analysis revealed that the cells from both R-15 and R-24 series of IFN-α resistant cells have 58 amino acid deletions in the extracellular sub domain 1 (SD1) of IFNAR1. In addition, cells from the R-17 series have 50 amino acids deletion in the sub domain 4 (SD4) of IFNAR1 protein leading to impaired activation of Tyk2 kinase. Using an infectious HCV cell culture model we show here that viral replication in the infected Huh-7 cells is relatively resistant to exogenous IFN-α. HCV infection itself induces defective Jak-Stat signaling and impairs Stat1 and Stat2 phosphorylation by down regulation of the cell surface expression of IFNAR1 through the endoplasmic reticulum (ER) stress mechanisms. The results of this study suggest that expression of cell surface IFNAR1 is critical for the response of HCV to exogenous IFN-α