National Institute of Pharmaceutical Education and Research, Rae Bareli

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Rae Bareli, India
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Singh S.,National Institute of Pharmaceutical Education and Research, Rae Bareli
International Journal of Pharmaceutical Sciences Review and Research | Year: 2010

The plant Borage (Borago officinalis L.) family-Boraginaceae, also known as "starflower" is an annual herb originating in Syria, but naturalized throughout the Mediterranean region, as well as Asia Minor, Europe, North Africa, and South America. Traditionally borage was cultivated for culinary and medicinal uses, although today commercial cultivation is mainly as an oilseed which contains gamma-linolenic acid and other fatty acids. Naturopathic practitioners uses of borage for regulation of metabolism and the hormonal system, and consider it to be a good remedy for PMS and menopause symptoms such as the hot flash. Borage is sometimes indicated to alleviate and heal colds, bronchitis, and respiratory infections in general for its anti-inflammatory and balsamic properties. The flowers can be prepared in infusion to take advantage of its medicinal properties. The oleic and palmitic acid of borage may also confer a hypocholesterolemic effect. In Unani system of medicine the plant is very popular as Gaozaban and used in various khameeras for cardioprotection.


Bhat S.A.,CSIR - Central Electrochemical Research Institute | Goel R.,CSIR - Central Electrochemical Research Institute | Shukla R.,CSIR - Central Electrochemical Research Institute | Hanif K.,CSIR - Central Electrochemical Research Institute | Hanif K.,National Institute of Pharmaceutical Education and Research, Rae Bareli
Molecular Neurobiology | Year: 2016

Neuroinflammation, sustained by astroglial and microglial activation, is the preceding event in neurodegeneration. Various clinical reports showed better neuroprotection by AT1 receptor blockade (ARB) than angiotensin-converting enzyme inhibition (ACEi), but experimental evidences and associated mechanism for this observation are lacking. Therefore, we investigated the effect of ARB, using Candesartan, and ACEi, using Perindopril, in equimolar concentrations in astroglial (C6) and microglial (BV2) cells employing lipopolysaccharide (LPS) to induce neuroinflammation. Further, Candesartan (0.1 mg/kg) and Perindopril (0.1 mg/kg) were orally administered in male SD rats for five consecutive days, and on the fifth day, rats were challenged with LPS (i.p.; 250 μg/kg) and sacrificed after 24 h. LPS-induced neuroinflammation (increased astroglial and microglial activation, IκBα degradation, NFкB nuclear translocation, STAT3 activation, and TNF-α release) was more efficiently prevented by Candesartan (even at lower concentration of 1 nM) than by Perindopril (1 μM) in both the cell types and in rat model of neuroinflammation. In addition, increased AT1 receptor (AT1R) and decreased AT2 receptor (AT2R) expression was observed in LPS-induced neuroinflammation in both in vitro and in vivo studies. Candesartan, as compared to Perindopril, increased the expression of AT2R in both the experimental conditions. Interestingly, concomitant blockade of AT2R by PD123319 significantly reversed the beneficial effects of Candesartan in both the cell types and in rat model of neuroinflammation. Finally, our data emphasize that superiority of Candesartan as compared to Perindopril is due to better activation of AT2R which results in PP2A activation, IκBα stabilization, and suppression of NFкB and STAT3 inflammatory signaling. © 2015, Springer Science+Business Media New York.


Bhat S.A.,CSIR - Central Electrochemical Research Institute | Goel R.,CSIR - Central Electrochemical Research Institute | Shukla R.,CSIR - Central Electrochemical Research Institute | Hanif K.,CSIR - Central Electrochemical Research Institute | Hanif K.,National Institute of Pharmaceutical Education and Research, Rae Bareli
Brain, Behavior, and Immunity | Year: 2017

Studies have demonstrated separately that hypertension is associated with platelet activation in the periphery (resulting in accumulation and localized inflammatory response) and glial activation in the brain. We investigated the contribution of platelets in brain inflammation, particularly glial activation in vitro and in a rat model of hypertension. We found that HTN increased the expression of adhesion molecules like JAM-1, ICAM-1, and VCAM-1 on brain endothelium and resulted in the deposition of platelets in the brain. Platelet deposition in hypertensive rats was associated with augmented CD40 and CD40L and activation of astrocytes (GFAP expression) and microglia (Iba-1 expression) in the brain. Platelets isolated from hypertensive rats had significantly higher sCD40L levels and induced more prominent glial activation than platelets from normotensive rats. Activation of platelets with ADP induced sCD40L release and activation of astrocytes and microglia. Moreover, CD40L induced glial (astrocytes and microglia) activation, NFкB and MAPK inflammatory signaling, culminating in neuroinflammation and neuronal injury (increased apoptotic cells). Importantly, injection of ADP-activated platelets into normotensive rats strongly induced activation of astrocytes and microglia and increased plasma sCD40L levels compared with control platelets. On the contrary, inhibition of platelet activation by Clopidogrel or disruption of CD40 signaling prevented astrocyte and microglial activation and provided neuroprotection in both in vivo and in vitro conditions. Thus, we have identified platelet CD40L as a key inflammatory molecule for the induction of astrocyte and microglia activation, the major contributors to inflammation-mediated injury in the brain. © 2016 Elsevier Inc.


Taneja I.,Academy of Scientific and Industrial Research | Taneja I.,CSIR - Central Electrochemical Research Institute | Erukala M.,National Institute of Pharmaceutical Education and Research, Rae Bareli | Raju K.S.R.,Academy of Scientific and Industrial Research | And 5 more authors.
Bioanalysis | Year: 2013

Malaria is the leading parasitic disease in emerging countries. Therapeutic drug monitoring of antimalarial drugs is becoming increasingly important due to their spreading resistance. Measuring systemic antimalarial drug concentrations is also vital for safety and PK evaluations during clinical development. The dried blood spot (DBS) technique is a convenient alternative sample-collection method to venipuncture, especially in resource-limited areas where the clinical studies of antimalarials are usually carried out. Various bioanalytical methods for antimalarial drug estimation utilizing DBS sampling have been reported. This review discusses the applicability and relevance of DBS in quantitative assessment of antimalarial drugs, the advantages and drawbacks of DBS, and the difficulties encountered during its implementation. © 2013 Future Science Ltd.


Koley D.,CSIR - Central Electrochemical Research Institute | Koley D.,Academy of Scientific and Innovative Research | Srinivas K.,CSIR - Central Electrochemical Research Institute | Krishna Y.,CSIR - Central Electrochemical Research Institute | Gupta A.,National Institute of Pharmaceutical Education and Research, Rae Bareli
RSC Advances | Year: 2014

A direct Mannich type diastereoselective biomimetic cyclization using acetal as a pro-nucleophile leading to the hydroxymethyl substituted bicyclic framework of various bicyclic alkaloids is presented. Following this protocol, total synthesis of (±)-epilupinine and formal syntheses of (±)-laburnine, (±)-isoretronecanol and (±)-tashiromine are described. © 2013 The Royal Society of Chemistry.


Wahajuddin,CSIR - Central Electrochemical Research Institute | Wahajuddin,National Institute of Pharmaceutical Education and Research, Rae Bareli | Arora S.,National Institute of Pharmaceutical Education and Research, Rae Bareli
International Journal of Nanomedicine | Year: 2012

A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to be resolved before they can be moved from bench top to bedside. © 2012 Wahajuddin and Arora, publisher and licensee Dove Medical Press Ltd.


Kaur G.,CSIR - Central Electrochemical Research Institute | Kaur G.,Integral University | Singh N.,CSIR - Central Electrochemical Research Institute | Lingeshwar P.,National Institute of Pharmaceutical Education and Research, Rae Bareli | And 4 more authors.
Pulmonary Pharmacology and Therapeutics | Year: 2015

Recently, inhibition of poly (ADP-ribose) polymerase-1 (PARP1) was shown to be protective in experimental pulmonary hypertension (PH) and prevented right ventricular hypertrophy (RVH) associated with it. However, molecular mechanism behind cardioprotection by PARP1 inhibition in PH still needs detailed exploration. Therefore, effect of inhibition of PARP1 on the right ventricle (RV) dysfunction was studied in monocrotaline (MCT) induced PH model. Following a single dose administration of MCT (60mg/kg, s.c.), male Sprague-Dawley rats were treated with PARP1 inhibitor 1,5-Isoquinolinediol (ISO, 3mg/kg, i.p.) for 35 days for preventive study and from day 21-35 for curative study. RV pressure (RVP) and RVH were measured after 35 days. Histophathological studies, PARP1 activity, mRNA and protein expression were studied in isolated RV. Oxidative and nitosative stress, inflammation and Matrix metalloproteinases (MMPs)/Tissue inhibitor of metalloproteinase 2 (TIMP2) were also assessed. Mitochondrial dysfunction was studied by mitochondrial membrane permeability and estimation of Nicotinamide adenine dinucleotide (NAD) and Adenosine triphosphate (ATP). Apoptosis in RV was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cleaved PARP1 expression. PARP1 inhibition significantly reversed the increase in RVP and RVH in both preventive and curative treatment in the MCT-injected rats. ISO lowered oxidative and nitrosative stress and inflammation and restored the balance of MMPs/TIMP2 expression. PARP1 inhibition prevented mitochondrial dysfunction and the release of cell death factors from mitochondria. ISO also decreased apoptosis by decreasing number of TUNEL positive cells, caspase 3 activity and PARP1 cleavage in RV. Thus, PARP1 inhibition ameliorated PH induced RV hypertrophy and may emerge as a new therapeutic target for PH. © 2014 Elsevier Ltd.


Singh S.P.,CSIR - Central Electrochemical Research Institute | Wahajuddin,CSIR - Central Electrochemical Research Institute | Tewari D.,CSIR - Central Electrochemical Research Institute | Patel K.,National Institute of Pharmaceutical Education and Research, Rae Bareli | Jain G.K.,CSIR - Central Electrochemical Research Institute
Fitoterapia | Year: 2011

In the present study, we are reporting permeability and pharmacokinetics of nobiletin in rat plasma and brain, using a validated reverse phase high performance liquid chromatographic method. Protein precipitation method was used for the extraction of nobiletin and coumarin (IS) from rat plasma and brain tissue. The system was run in isocratic mode with mobile phase consisting of potassium dihydrogen ortho-phosphate (pH 4.5; 0.04 mM) and acetonitrile in ratio of 50:50, v/v. The total chromatographic run time was 9.0 min. The method was proved to be accurate and precise at linearity range of 0.05-10 μg/mL with a correlation coefficient (r) of ≥ 0.994 in rat plasma and ≥ 0.995 in rat brain. The intra- and inter-day precision and accuracy values are found to be within the assay variability limits as per the FDA guidelines. Nobiletin was found stable in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and long term storage in a freezer at - 70 ± 10 °C. Maximum concentrations of nobiletin in both plasma and brain were observed at 1 h after single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were 1.78 and 4.20 μg/mL, respectively. The AUC 0-t in plasma and brain were 7.49 and 20.66 μg•h/mL, respectively. The mean elimination half life (t 1/2) in plasma and brain were 1.80 and 11.42 h, respectively. The Parallel Artificial Membrane Permeability Assay (PAMPA) permeability of nobiletin was found to be high at both pH 4.0 and 7.0. © 2011 Elsevier B.V. All rights reserved.


Wahajuddin,CSIR - Central Electrochemical Research Institute | Wahajuddin,National Institute of Pharmaceutical Education and Research, Rae Bareli | Singh S.P.,CSIR - Central Electrochemical Research Institute | Raju K.S.R.,National Institute of Pharmaceutical Education and Research, Rae Bareli | And 3 more authors.
Malaria Journal | Year: 2011

Background: Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats. Methods. A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. In-situ permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC. Results: For nominal doses increasing in a 1:2:4 proportion, the Cmaxand AUC0-values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the Cmaxand the AUC 0-tvalues for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 ( 0.02) L/h/kg and 2.40 ( 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10-5 cm/s) in permeability study. Conclusions: The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the in-situ permeability study. © 2011 Wahajuddin et al; licensee BioMed Central Ltd.


PubMed | National Institute of Pharmaceutical Education and Research, National Institute of Pharmaceutical Education and Research, Rae Bareli, CSIR - Central Electrochemical Research Institute and Integral University
Type: | Journal: Pulmonary pharmacology & therapeutics | Year: 2016

Increased sympathetic nervous system (SNS) activity is associated with cardiovascular diseases but its role has not been completely explored in pulmonary hypertension (PH). Increased SNS activity is distinguished by elevated level of norepinephrine (NE) and activity of -Amino butyric acid Transminase (GABA-T) which degrades GABA, an inhibitory neurotransmitter within the central and peripheral nervous system. Therefore, we hypothesized that GABA-T may contribute in pathophysiology of PH by modulating level of GABA and NE. The effect of daily oral administration of GABA-T inhibitor, Vigabatrin (GVG, 50 and 75 mg/kg/day, 35 days) was studied following a single subcutaneous administration of monocrotaline (MCT, 60 mg/kg) in male SD rats. The pressure and hypertrophy of right ventricle (RV), oxidative stress, inflammation, pulmonary vascular remodelling were assessed after 35 days in MCT treated rats. The expression of GABA-T and HIF-1 was studied in lung tissue. The levels of plasma NE (by High performance liquid chromatography coupled with electrochemical detector; HPLC-ECD) and lung GABA (by liquid chromatography-mass spectrometry) were also estimated. GVG at both doses significantly attenuated increased in pressure (35.82 4.80 mm Hg, p < 0.001; 28.37 3.32 mm Hg, p < 0.001 respectively) and hypertrophy of RV, pulmonary vascular remodelling, oxidative stress and inflammation in lungs of MCT exposed rats. GVG also reduced the expression of GABA-T and HIF-1 in MCT treated rats. Increased NE level and decreased GABA level was also reversed by GVG in MCT exposed rats. GABA-T plays an important role in PH by modulating SNS activity and may be considered as a therapeutic target in PH.

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