Anju Katyal

Dr B.R Ambedkar Center for Biomedical research,University of Delhi, Dr B.R Ambedkar Center for Biomedical Research,University of Delhi, Faculty Member

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Malaria pathogenesis , Immunopathology and mechanistic studies of Hypobaric ,hypoxia,Ischemia, animal models , Alcoholic liver disease
Address: Dr B R Ambedkar center for Biomedical Research,University of Delhi

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Andrea Brugnami

Sapienza University of Roma

Maria-Georgia Ștefan

Harpreet Multani

Eldevan dos Santos Silva

Maha Lokman

Chi-Rei Wu

Yih-Dih Cheng

China Medical University,Taiwan

Lina Kury

Ellen Scotton

Fereshteh Farajdokht

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Papers by Anju Katyal

Antidepressant and anxiolytic like effects of Urtica dioica leaves in streptozotocin induced diabetic mice

Metabolic Brain Disease, Apr 27, 2018

The antidepressant-and anxiolytic-like effects of fluoxetine and clozapine in chronically isolate... more

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Involvement of angiotensin converting enzyme in cerebral hypoperfusion induced anterograde memory impairment and cholinergic dysfunction in rats

Neuroscience, Aug 1, 2008

Forebrain cholinergic dysfunction is the hallmark of vascular dementia (VaD) and Alzheimer's deme... more Forebrain cholinergic dysfunction is the hallmark of vascular dementia (VaD) and Alzheimer's dementia (AD) induced by cerebral hypoperfusion during aging. The aim of the present study is to evaluate the role of angiotensin converting enzyme (ACE) in cerebral hypoperfusion-induced dementia and cholinergic dysfunction. Chronic cerebral hypoperfusion (CHP) was induced by permanent bilateral common carotid artery (2VO) occlusion in rats. Chronic cerebral hypoperfusion resulted in anterograde memory impairment revealed from Morris water maze (MWM) and passive avoidance step through tasks (PA), which was significantly attenuated by ACE inhibitor, captopril. Cerebral hypoperfusion down-regulated the relative expression of cholinergic muscarinic receptor (ChM-1r) and choline acetyltransferase (ChAT) as well as up-regulated the angiotensin II type-1 receptor (AT-1) expression in hippocampus of vehicle treated CHP group on the 54th day post-hypoperfusion. The diminished number of presynaptic cholinergic neurons and the pyramidal neurons were evident from ChAT-immunofluorescence and the hematoxylin and eosin (H&E) staining studies respectively in hippocampal Cornu ammonis1 (CA1); region of vehicle-treated hypoperfused animals. Further the lipid peroxidation level was also found to be elevated in the hippocampus of the vehicle-treated group. Our results demonstrated that continuous captopril treatment (50 mg/kg, i.p. twice daily) for 15 days mitigated the hypoperfusion-induced cholinergic hypofunction and neurodegeneration in hippocampus. The present study robustly reveals that the angiotensinergic system plays a pivotal role in progression of neuronal death and memory dysfunctions during cerebral hypoperfusion.

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Data on retinoic acid and reduced serum concentration induced differentiation of Neuro-2a neuroblastoma cells

Data in Brief, Dec 1, 2018

The present data describe the relative neuro-2a cellular differentiation induced by reducing seru... more The present data describe the relative neuro-2a cellular differentiation induced by reducing serum concentration (0.1% FBS) in DMEM in the presence/absence of 20 μM retinoic acid (RA). Neurite outgrowth was observed within 24 h in DMEM supplemented with reduced serum and retinoic acid (GpIV). The CFSE based proliferation assay data signified cessation of neuro-2a cellular proliferation in GpIV. An increase in the number of cells arrested at G 0 /G 1 phase was also evident in GpIV and DMEM supplemented with 0.1% FBS (GpIII). Moreover, GpIV cells had improved mRNA and protein expression of Rbfox3/NeuN and choline acetyltransferase (ChAT).

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Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats

European Journal of Drug Metabolism and Pharmacokinetics, Sep 1, 2004

The modulatory potential of noscapine, an opium alkaloid was assessed on the ethanol-induced chan... more The modulatory potential of noscapine, an opium alkaloid was assessed on the ethanol-induced changes in hepatic drug metabolizing enzyme systems, glutathione content and microsomal lipid peroxidation, Noscapine was administered orally to male Wistar rats at a dose level of ZOO rng/kg bw alone as well as in combination with 50% ethanol (v/v) for 5 days. Noscapine administration was associated with a-91 % decrease in hepatic microsomal cytochrome P-450 content. A decline of-36% was observed in the NADPH-cytochrome c reductase activity on noscapine administration. The lowering of cytochrome P-450 levels on noscapine administration was accompanied by a concomitant increase in heme oxygenase activity as well as serum bilirubin levels. Our results indicate that the combination dosage of noscapine and ethanol antagonised the ethanol-induced elevation of cytochrome P-450 levels. Noscapine fed rats had decreased glutathione (GSH) content and enhanced lipid peroxidation compared to control rats as indexed by MDA method. Further, noscapine and ethanol coexposure produced a more pronounced elevation in lipid peroxidation and the glutathione levels also decreased significantly. We speculate on the basis of our results that the significant enhancement of lipid peroxidation on combination dosage of noscapine and ethanol is a consequence of depletion of glutathione to certain critical levels. The inhibition of glutathione-S-transferase (GST) as well as lowering of cytochrome P-450 suggests that the biotransformation of noscapine and ethanol is significantly altered following acute coexposures.

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Modification of mouse A2M B (620-792) and A2M N (168-230) by malondialdehyde and acetaldehyde attenuates the proteinase and TGF-β1 binding ability of A2MB

FEBS Letters, Feb 12, 2011

Acetaldehyde and malondialdehyde react covalently with cellular proteins forming protein-malondia... more Acetaldehyde and malondialdehyde react covalently with cellular proteins forming protein-malondialdehyde-acetaldehyde adducts thus modulating their biochemical functions. Alpha-2 macroglobulin, an acute phase protein produced by liver binds to cytokines, growth factors and neutralizes proteinases. In this study we examined the formation of MAA adducts of N-terminal and bait region of mouse A2M and their effect on modulating its proteinase and TGF-b1 binding activities. Adduct formation abrogated the binding of bait region with TGF-b1, trypsin, and elastase. TGF-b1 induced NO production was also suppressed. Acetaldehyde and MDA adduction of A2M may have physiological consequences in alcoholic patients.

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Cu Nanoparticles in Ionic Liquid: An Easy and Efficient Catalyst for Addition–Elimination Reaction Between Active Methylene Compounds and Imines in an Ionic Liquid

Catalysis Letters, Apr 7, 2009

Here, we report a novel preparation of copper nanoparticles in ionic liquid and its use in the ad... more Here, we report a novel preparation of copper nanoparticles in ionic liquid and its use in the addition elimination reaction. Powder X-ray diffraction, transmission electron microscopy and quassi elastic light scattering techniques revealed the formation and size of copper nanoparticles and its use for the addition-elimination reaction between active methylene compounds and imines using an ionic liquid in presence of NEt 3 to yield the corresponding products in high yields and in short duration was done.

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Galactosylated gelatin nanovectors of doxorubicin inhibit cell proliferation and induce apoptosis in hepatocarcinoma cells

Anti-Cancer Drugs, Sep 1, 2012

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Effect of Ca2EDTA on Zinc Mediated Inflammation and Neuronal Apoptosis in Hippocampus of an In Vivo Mouse Model of Hypobaric Hypoxia

PLOS ONE, Oct 23, 2014

Background: Calcium overload has been implicated as a critical event in glutamate excitotoxicity ... more Background: Calcium overload has been implicated as a critical event in glutamate excitotoxicity associated neurodegeneration. Recently, zinc accumulation and its neurotoxic role similar to calcium has been proposed. Earlier, we reported that free chelatable zinc released during hypobaric hypoxia mediates neuronal damage and memory impairment. The molecular mechanism behind hypobaric hypoxia mediated neuronal damage is obscure. The role of free zinc in such neuropathological condition has not been elucidated. In the present study, we investigated the underlying role of free chelatable zinc in hypobaric hypoxia-induced neuronal inflammation and apoptosis resulting in hippocampal damage. Methods: Adult male Balb/c mice were exposed to hypobaric hypoxia and treated with saline or Ca 2 EDTA (1.25 mM/kg i.p) daily for four days. The effects of Ca 2 EDTA on apoptosis (caspases activity and DNA fragmentation), pro-inflammatory markers (iNOS, TNF-a and COX-2), NADPH oxidase activity, poly(ADP ribose) polymerase (PARP) activity and expressions of Bax, Bcl-2, HIF-1a, metallothionein-3, ZnT-1 and ZIP-6 were examined in the hippocampal region of brain. Results: Hypobaric hypoxia resulted in increased expression of metallothionein-3 and zinc transporters (ZnT-1 and ZIP-6). Hypobaric hypoxia elicited an oxidative stress and inflammatory response characterized by elevated NADPH oxidase activity and up-regulation of iNOS, COX-2 and TNF-a. Furthermore, hypobaric hypoxia induced HIF-1a protein expression, PARP activation and apoptosis in the hippocampus. Administration of Ca 2 EDTA significantly attenuated the hypobaric hypoxia induced oxidative stress, inflammation and apoptosis in the hippocampus. Conclusion: We propose that hypobaric hypoxia/reperfusion instigates free chelatable zinc imbalance in brain associated with neuroinflammation and neuronal apoptosis. Therefore, zinc chelating strategies which block zinc mediated neuronal damage linked with cerebral hypoxia and other neurodegenerative conditions can be designed in future.

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Novel Cytosolic Allergens of Aspergillus fumigatus Identified from Germinating Conidia

Journal of Proteome Research, Oct 7, 2010

Aspergillus fumigatus is the common cause of allergic broncho-pulmonary aspergillosis (ABPA) and ... more Aspergillus fumigatus is the common cause of allergic broncho-pulmonary aspergillosis (ABPA) and most of the allergens have been described from its secreted fraction. In the present investigation, germinating conidial cytosolic proteins of A. fumigatus were extracted from a 16 h culture. The proteome from this fraction was developed, and immuno-blots were generated using pooled ABPA patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; sera. Well separated Immunoglobulin-E (IgE) and Immunoglobulin-G (IgG) reactive spots were picked from corresponding 2DE gels and subjected to mass spectrometric analysis. As a result, 66 immuno-reactive proteins were identified from two geographically different strains (190/96 and DAYA) of A. fumigatus. Only 3 out of 66 proteins reacted with IgG, and the remaining 63 proteins were found to be IgE reactive. These 63 IgE-reactive cytosolic proteins from germinating conidia included 2 already known (Asp f12 and Asp f22) and 4 predicted allergens (Hsp88, Hsp70, malate dehydrogenase, and alcohol dehydrogenase) based on their homology with other known fungal allergens. In view of this, the panel of presently identified IgE-reactive novel proteins holds the potential of providing a basis for the wider diagnostic application in assay for allergic aspergillosis. We could demonstrate that recombinantly expressed proteins from this panel showed consistent reactivity with IgE of individual sera of ABPA patients. The recombinantly expressed proteins may also be useful in desensitization therapy of allergic disorders including ABPA.

Synthesis and characterization of silver and gold nanoparticles in ionic liquid

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Jul 1, 2009

In this paper, we report the reduction of silver and gold salts by methanolic solution of sodium ... more

“Endophytes: an unexplored treasure to combat Multidrug resistance”

Phytomedicine Plus, 2022

Cardiac autonomic function in acutely nitric oxide deficient hypertensive rats: role of the sympathetic nervous system and oxidative stress

Canadian Journal of Physiology and Pharmacology, Dec 1, 2011

We evaluated the role of the sympathetic nervous system and oxidative stress in hemodynamic and a... more We evaluated the role of the sympathetic nervous system and oxidative stress in hemodynamic and autonomic control after acute inhibition of the synthesis of nitric oxide, using intravenous (i.v.) injection of 30 mg·kg–1 NG-nitro-l-arginine methyl ester (L-NAME) in adult Wistar rats. Baroreflex sensitivity (BRS) and heart rate variability (HRV) were measured as indices of cardiac autonomic control, before and after L-NAME treatment in rats with intact autonomic innervation, and in rats with chemical sympathectomy by 6-hydroxydopamine. Serum malondialdehyde (MDA) was measured as a marker of oxidative stress. In control rats, L-NAME treatment resulted in a significant rise in blood pressure, augmentation of BRS, and enhanced serum MDA. HRV showed an attenuation of total spectral power and high frequency spectral power, along with a rise of the low to high frequency ratio (LF:HF). Administration of L-NAME produced a pressor response even in sympathectomised rats, but augmented BRS was not observed, and the high frequency spectral power showed an increase, in addition to a significant decline of LF:HF and serum MDA. We therefore conclude that even though pressor response was unaffected, reversal of cardiac autonomic responses and decline in oxidative stress following sympathectomy in L-NAME-treated rats reflects a significant role for sympathetic innervation in acute L-NAME-induced hypertension.

Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer

Anti-Cancer Drugs, 2014

Parenteral administration of recombinant interferon-a-2b (rINF-a-2b) at a dose of 50 ¾ 10 6 IU on... more Parenteral administration of recombinant interferon-a-2b (rINF-a-2b) at a dose of 50 ¾ 10 6 IU once a week for 8 weeks is recommended for ovarian cancer. However, short half-life, small therapeutic index and proteolytic degradation cause fluctuations in plasma level and pose barriers in the development of a clinically viable dosage form. Therefore, in the present investigation, fluorescein isothiocynate-tagged rINF-a-2b was loaded into stearic acid (*rINF-a-2b-SMs), pectin (*rINF-a-2b-PMs) and gelatin (*rINF-a-2b-GMs) microspheres. Parameters such as particle size, B potential, encapsulation efficiency and in-vitro release were studied to follow the optimization process. The formulation, *rINF-a-2b-GMs of particle size 8.3±2.1 lm with an encapsulation efficiency of 76.0±7.4%, offered 97.4% of *rINF-a-2b release at 288 h. Thus, negatively charged extended-release formulation *rINF-a-2b-GMs was then tethered with a gradient concentration (5-20 mg/ml) of a cationic arginine-rich protein stabilizer, protamine sulphate (Pt). The nanoformulation, *rINF-a-2b-Pt-GMs-15 superimposed with 15 mg/ml of Pt, released 95.0% of *rINF-a-2b at 336 h and was designated as the optimized formulation. The optimized formulation also conserved the primary and secondary structure of *rINF-a-2b as analysed by gel electrophoresis and circular dichroism. Moreover, in-vitro cytotoxicity analysis of SKOV3 cells of the optimized nanoformulation reported significantly (one-way analysis of variance test, P < 0.05) lower IC 50 (414.3 IU/ml) compared with *rINF-a-2b-GMs (514.3 IU/ml) and pure rINF-a-2b (628.6 IU/ml) at 72 h by offering a prolonged cytotoxic effect. Therefore, *rINF-a-2b-Pt-GMs-15, a promising nanomedicine, warrants further in-depth in-vivo study to scale up the technology for clinical translation. Anti-Cancer Drugs 25:63-71

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Hypericum perforatum (ethanolic extract) ameliorates simulated hypobaric hypoxia induced oxidative stress and neuronal damage in brains of Balb/c mice

Asian Journal of Medical Sciences, Mar 1, 2018

Background: Hypobaric hypoxia refers to lower oxygen availability at high altitudes and is the ca... more Background: Hypobaric hypoxia refers to lower oxygen availability at high altitudes and is the cause of high altitude illness. Drugs such as acetazolamide and dexamethasone provide symptomatic relief and are associated with undesired side effects. Plant extracts such as Hypericum perforatum, which are documented to have neuromodulatory role can be more beneficial in ameliorating high altitude illness. Aims and Objective: Progressive cognitive decline is the hallmark characteristic of hypobaric hypoxia induced neuropathology attributed to ensuing oxidative stress and subsequent hippocampal damage. We have explored the efficacy of ethanolic extracts of Hypericum perforatum in amelioration of hypobaric hypoxia induced oxidative stress and associated behavioral deficits in mice. Material and Methods: Male Balb/c mice were exposed to simulated altitude of 25,000 ft. for 7 days (6 hr. per day) in a specially designed chamber. Ethanolic extract of Hypericum perforatum (HPE)(25mg/kg of body weight) was given orally prior to Hypobaric exposure and effects were compared to Hypobaric and control groups. Results: Animals exposed to hypobaric hypoxia showed sign of cognitive deterioration at day 3 and day 7 in the Elevated Plus Maze and Passive Avoidance Step through behavioral paradigms as compare to normoxic animals. Administration of HPE was able to alleviate the amnesic effect in treatment group, indicated by reduction in transfer latencies at day 3(IR-3 =-0.66±0.07) and day 7 IR-7 =-0.81±0.06) in elevated plus maze task and increased passive avoidance step through latency at day 3, (IR-3 = 3.23±0.67),as compared to hypoxic mice. Hypoxia group of animals suffered significant oxidative stress compared to normoxic mice as indicated by up-regulated malondialdehyde and total nitrite levels in hippocampal homogenates. The plasma lactate dehydrogenase activity was also increased following hypoxia indicating tissue damage. Co-treatment with HPE in simulated hypobaric hypoxia insult for seven days resulted in significant reduction in malondialdehyde, total nitrites and plasma LDH levels in animals. Conclusion: Hypericum perforatum extract improves cognitive performance in hypobaric hypoxia exposed mice with a concomitant reduction in oxidative stress burden suggesting its plausible use for preventing high altitude illness.

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Non-small cell lung cancer tumour antigen, MUC-1 peptide-loaded non-aggregated poly (lactide-co-glycolide) nanoparticles augmented cellular uptake in mouse professional antigen-presenting cells: optimisation and characterisation

Journal of Microencapsulation, Nov 27, 2019

(2019): Non-small cell lung cancer tumour antigen, MUC-1 peptide loaded non-aggregated poly (lact... more

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The treatment of skin carcinoma, induced by UV B radiation, using 1-oxo-5β, 6β-epoxy-witha-2-enolide, isolated from the roots of Withania somnifera, in a rat model

Phytomedicine, Jul 1, 2004

Histopathological studies of the cutaneous tissues of Wistar rats exposed to UV B radiation (294 ... more Histopathological studies of the cutaneous tissues of Wistar rats exposed to UV B radiation (294 nm) for 20 days and rats exposed to UV B radiation for 20 days, followed by topical treatment with benzoyl peroxide, a tumor promoter (20 mg/animal/0.2 ml acetone) twice a week for 1 month, and kept under observation for 12 weeks, demonstrate the development of malignancy. Pretreatment of the animals with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide (20 mg/kg bwt.), isolated from the roots of Withania somnifera, prior to exposing the animals to UV B radiation, prevents the incidence of skin carcinoma. The administration of 1-oxo-5beta, 6beta-epoxy-witha-2-enolide, to the animals after exposing them to UV B radiation/UV B radiation and benzoyl peroxide also prevents the occurrence of malignancy in the cutaneous tissue. Immunohistochemical staining of the cutaneous tissues of rats exposed to UV B radiation show the presence of p53 + foci (clusters of cells containing the mutated p53 protein), whereas an absence of p53 + foci is observed in animals pretreated with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide. These results prove that 1-oxo-5beta, 6beta-epoxy-witha-2-enolide has the potential for acting as an effective agent to prevent the incidence of skin carcinoma induced by UV B radiation.

Long-circulating poly(ethylene glycol)-grafted gelatin nanoparticles customized for intracellular delivery of noscapine

Anti-Cancer Drugs, Jul 1, 2011

Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED 50 (3... more Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED 50 (300-600 mg/kg), whereas intravenous administration (10 mg/kg) results in rapid elimination of the drug with a half-life of 0.39 h. Hence, the development of long-circulating injectable nanoparticles can be an interesting option for designing a viable formulation of noscapine for anticancer activity. Noscapine-enveloped gelatin nanoparticles and poly(ethylene glycol)-grafted gelatin nanoparticles were constructed and characterized. Data indicate that smooth and spherical shaped nanoparticles of 127 ± 15 nm were engineered with maximum entrapment efficiency of 65.32 ± 3.81%. Circular dichroism confirms that nanocoacervates retained the a-helical content of gelatin in ethanol whereas acetone favored the formation of a random coil. Moreover, the Fourier transform infrared and powder X-ray diffraction pattern prevents any significant change in the noscapine-loaded gelatin nanoparticles in comparison with individual components. In-vitro release kinetic data suggest a first-order release of noscapine (85.1%) from gelatin nanoparticles with a release rate constant of 7.611 ¾ 10-3. It is to be noted that there is a 1.43-fold increase in the area under the curve up to the last sampling point for the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles over the noscapineloaded gelatin nanoparticles and a 13.09-fold increase over noscapine. Cytotoxicity analysis of the MCF-7 cell line indicated that the IC 50 value of the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles was equivalent to 20.8 lmol/l, which was significantly (P < 0.05) lower than the IC 50 value of the noscapineloaded gelatin nanoparticles (26.3 lmol/l) and noscapine (40.5 lmol/l). Noscapine-loaded poly(ethylene glycol)grafted gelatin nanoparticles can be developed as a promising therapeutic agent for the management of breast cancer. Anti-Cancer Drugs 22:543-555

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Targeted activation of transcription in vivo through hairpin-triplex forming oligonucleotide in Saccharomyces cerevisiae

Molecular and Cellular Biochemistry, Oct 1, 2005

Triplex forming oligonucleotides (TFO) are known to be potential agents for modifying gene functi... more Triplex forming oligonucleotides (TFO) are known to be potential agents for modifying gene function. In most instances they are utilized for repression of transcription. However hybrid molecules containing cis-acting elements in a duplex DNA in a hairpin form contiguously with the TFO can bind transcription factors in vitro. In the present manuscript we demonstrate that hairpin-TFO can be employed in vivo for targeted activation of gene expression of two genes mapping on chromosome XI of Saccharomyces cerevisiae. The cis-acting GAL4 protein-binding site contained in the hairpin-TFO is targeted in vivo to the 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; upstream sequence of STE6 and CBT1 genes that are transcribed in opposite directions and share a poly(pu/py) sequence that can form triple helical structure. The hairpin-TFO is targeted to this site and promotes the activation of both the genes. These results demonstrate four important aspects relating to activation of gene expression: (i) accessibility of duplex DNA packaged into chromatin to triplex forming sequences in vivo, (ii) the potential use of hairpin-TFO in therapeutics by activation of transcription in vivo, (iii) Sharing of transcription factors between two genes transcribed in opposite directions and (iv) specific activation of genes even when their cognate site is not covalently linked to the gene being activated.

Enhanced noscapine delivery using estrogen-receptor-targeted nanoparticles for breast cancer therapy

Anti-Cancer Drugs, Jul 1, 2014

Noscapine (Nos), an orally available plant-derived antitussive alkaloid, is in phase II clinical ... more Noscapine (Nos), an orally available plant-derived antitussive alkaloid, is in phase II clinical trials for cancer chemotherapy. It has extensively been shown to inhibit tumor growth in nude mice bearing human xenografts of hematopoietic, breast, lung, ovarian, brain, and prostate origin. However, high tumor-suppressive Nos dosages encumber the development of oral controlled-release formulations because of a short biological half-life (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 h), poor absorption, low aqueous solubility, and extensive first-pass metabolism. Here, we present the design, fabrication, optimization, characterization, and biological evaluation of estrone-conjugated noscapine-loaded gelatin nanoparticles (Nos-ES-GN) for targeting estrogen-receptor-positive breast cancer MCF-7 cells. Gelatin nanoparticles (GN) were a uniformly compact size, stable at physiological pH, and showed a drug entrapment efficiency of 66.1±5.9 and 65.2±5.6% for Nos-GN and Nos-ES-GN, respectively. The secondary structure of gelatin nanocoacervates was predicted using circular dichroism and in-silico molecular modeling. Our data suggest that ethanol-fabricated GN retained the α-helical content of gelatin, whereas acetone favored the formation of random coils. The conjugation of estrone to Nos-GN did not affect the release rate of the drug, and both formulations followed first-order release kinetics with an initial burst, followed by a slow release. The IC50 value of Nos-ES-GN was 21.2 μmol/l, which was ∼50% lower than the free drug (43.3 μmol/l), suggesting targeted drug delivery. Our cell uptake study carried out in an estrogen-receptor-positive (MCF-7) and negative (MDA-MB-231) cancer cell lines showed greater accumulation of Nos-ES-GN in MCF-7 cells instead of MDA-MB-231 cells. Our data indicated that estrone-conjugated nanoparticles may potentially be used for targeting breast cancer cells.

Cholinergic receptor blockade by scopolamine and mecamylamine exacerbates global cerebral ischemia induced memory dysfunction in C57BL/6J mice

Nitric Oxide, Dec 1, 2014

Global cerebral ischemia/reperfusion (GCI/R) injury encompasses complex pathophysiological sequal... more Global cerebral ischemia/reperfusion (GCI/R) injury encompasses complex pathophysiological sequalae, inducing loss of hippocampal neurons and behavioural deficits. Progressive neuronal death and memory dysfunctions culminate from several different mechanisms like oxidative stress, excitotoxicity, neuroinflammation and cholinergic hypofunction. Experimental evidences point to the beneficial effects of cholinomimetic agents such as rivastigmine and galantamine in improving memory outcomes following GCI/R injury. However, the direct implications of muscarinic and nicotinic receptor blockade during global cerebral ischemia/reperfusion injury have not been investigated. Therefore, we evaluated the relative involvement of muscarinic and nicotinic receptors in spatial/associative memory functions and neuronal damage during global cerebral ischemia reperfusion injury. The outcomes of present study support the idea that preservation of both muscarinic and nicotinic receptor functions is essential to alleviate hippocampal neuronal death in CA1 region following global cerebral ischemia/reperfusion injury.

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Antidepressant and anxiolytic like effects of Urtica dioica leaves in streptozotocin induced diabetic mice

Metabolic Brain Disease, Apr 27, 2018

The antidepressant-and anxiolytic-like effects of fluoxetine and clozapine in chronically isolate... more

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Involvement of angiotensin converting enzyme in cerebral hypoperfusion induced anterograde memory impairment and cholinergic dysfunction in rats

Neuroscience, Aug 1, 2008

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Data on retinoic acid and reduced serum concentration induced differentiation of Neuro-2a neuroblastoma cells

Data in Brief, Dec 1, 2018

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Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats