Chaudhary S.,Jamia Hamdard University |
Parvez S.,Jamia Hamdard University
Neuroscience | Year: 2012
Valproic acid (VPA), a branched short-chain fatty acid, is generally used as an antiepileptic drug and a mood stabilizer. VPA is a relatively safe drug, but its use in higher concentrations is associated with idiosyncratic neurotoxicity. Investigations involving cerebral cortex and cerebellum can shed light on whether neurotoxicity induced by branched chain fatty acids like VPA is mediated by oxidative stress. The aim of our investigation was to evaluate the neurotoxic potential of VPA by using preparation of cerebral cortex and cerebellum of young rats as an in vitro model. Oxidative stress indexes such as lipid peroxidation (LPO) and protein carbonyl (PC) formation were evaluated to visualize whether the first line of defence was breached. The levels of oxidative stress markers, LPO and PC were significantly elevated. Non-enzymatic antioxidants' effect was also demonstrated as a significant depletion in reduced glutathione (GSH) and non-protein thiol activity (NP-SH), but there was no significant increase or decrease in the concentrations of total thiol (T-SH) and protein thiol (P-SH). VPA also showed significant reduction in the activities of glutathione metabolizing enzymes such as glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) in cerebellum and cerebral cortex. A significant elevation was also observed in the activity of xanthine oxidase (XO). Some neurotoxicity biomarkers were investigated in which the activity of acetylcholinesterase (AChE) and sodium-potassium ATPase (Na+, K+-ATPase) was decreased and monoamine oxidase (MAO) was increased. These results indicate that VPA induces oxidative stress by compromising the antioxidant status of the neuronal tissue. Further studies are required to decipher the cellular and molecular mechanisms of branched chain fatty acid-induced neurotoxicity. © 2012 IBRO.
Pandita D.,Jamia Hamdard University
AAPS PharmSciTech | Year: 2011
The current research work investigates the potential of solid lipid nanoparticles (SLNs) in improving the oral bioavailability of paclitaxel. Paclitaxel-loaded SLNs (PTX-SLNs) were prepared by modified solvent injection method using stearylamine as lipid, soya lecithin and poloxamer 188 as emulsifiers. SLNs were characterized in terms of surface morphology, size and size distribution, surface chemistry and encapsulation efficiency. Pharmacokinetics and bioavailability studies were conducted in male Swiss albino mice after oral administration of PTX-SLNs. SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The mean particle size of SLNs was 96 ± 4.4 nm with a low polydispersity index of 0.162 ± 0.04 and zeta potential of 39.1 ± 0.8 mV. The drug entrapment efficiency was found to be 75.42 ± 1.5% with a loading capacity of 31.5 ± 2.1% (w/w). Paclitaxel showed a slow and sustained in vitro release profile and followed Higuchi kinetic equations. After oral administration of the PTX-SLNs, drug exposure in plasma and tissues was ten- and twofold higher, respectively, when compared with free paclitaxel solution. PTX-SLNs produced a high mean C (max) (10,274 ng/ml) compared with that of free paclitaxel solution (3,087 ng/ml). The absorbed drug was found to be distributed in liver, lungs, kidneys, spleen, and brain. The results suggested that PTX-SLNs dispersed in an aqueous environment are promising novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral delivery of paclitaxel as observed by in vivo toxicity studies.
Khan R.,Jamia Hamdard University |
Sultana S.,Jamia Hamdard University
Chemico-Biological Interactions | Year: 2011
Colon cancer is the major health hazard related with high mortality and it is a pathological consequence of persistent oxidative stress and inflammation. Farnesol, an isoprenoid alcohol, has been shown to possess antioxidant, anti-inflammatory and chemopreventive properties. The present study was performed to evaluate the protective efficacy of farnesol against 1,2-dimethylhydrazine (DMH) induced oxidative stress, inflammatory response and apoptotic tissue damage. Farnesol was administered once daily for seven consecutive days at the doses of 50 and 100 mg/kg body weight in corn oil. On day 7, a single injection of DMH was given subcutaneously in the groin at the dose of 40 mg/kg body weight. Protective effects of farnesol were assessed by using caspase-3 activity, tissue lipid peroxidation (LPO) and antioxidant status as end point markers. Further strengthening was evident on histopathological observations used to assess the protective efficacy of farnesol. Prophylactic treatment with farnesol significantly ameliorates DMH induced oxidative damage by diminishing the tissue LPO accompanied by increase in enzymatic viz., superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) and non-enzymatic viz., reduced glutathione (GSH) antioxidant status. Farnesol supplementation significantly decreased caspase-3 activity in colonic tissue. Histological findings also revealed that pretreatment with farnesol significantly reduced the severity of submucosal edema, regional destruction of the mucosal layer and intense infiltration of the inflammatory cells in mucosal and submucosal layers of the colon. The data of the present study suggest that farnesol effectively suppress DMH induced colonic mucosal damage by ameliorating oxidative stress, inflammatory and apoptotic responses. © 2011 Elsevier Ireland Ltd. All rights reserved.
Vishnoi S.,Jamia Hamdard University |
Raisuddin S.,Jamia Hamdard University |
Parvez S.,Jamia Hamdard University
Neuroscience and Biobehavioral Reviews | Year: 2016
New information acquired by our brain is stored in the form of two types of memories: short term memory (STM) and long term memory (LTM). Initially, Synaptic and Capture hypothesis has been proposed to describe the synaptic changes that occur during memory formation. However, recently Behavioral Tagging hypothesis was proposed that relies on the setting of a learning tag and the synthesis of plasticity related proteins (PRPs). Behavioral Tagging has its roots in Synaptic and Capture hypothesis. It seeks to explain that how a learning tag produced as a result of weak training can be paired up with PRPs (formed as a result of novelty) and can lead to long lasting memories. We have focused on describing behavioral paradigms that have been used for establishing the model of “Behavioral Tagging” and the molecules which qualify for potential PRP candidature. © 2016 Elsevier Ltd
Vohora D.,Jamia Hamdard University |
Bhowmik M.,Jamia Hamdard University
Frontiers in Systems Neuroscience | Year: 2012
Histamine H3 receptor (H3R) antagonists/ inverse agonists possess potential to treat diverse disease states of the central nervous system (CNS). Cognitive dysfunction and motor impairments are the hallmark of multifarious neurodegenerative and/or psychiatric disorders. This review presents the various neurobiological/ neurochemical evidences available so far following H3.R.antagonists, in the pathophysiology of Alzheimer's disease (AD), attention-deficit hyperactivity disorder (ADHD), schizophrenia and drug abuse each of which is accompanied by deficits of some aspects of cognitive and/or motor functions. Whether the H3.R inverse agonism modulates the neurochemical basis underlying the disease condition or affects only the cognitive/motor component of the disease process is discussed with the aim to provide a rationale for their use in diverse disease states that are interlinked and are accompanied by some common motor, cognitive and attentional deficits.
Bhowmik M.,Jamia Hamdard University |
Khanam R.,Jamia Hamdard University |
Vohora D.,Jamia Hamdard University
British Journal of Pharmacology | Year: 2012
The central histaminergic actions are mediated by H1, H 2, H3 and H4 receptors. The histamine H 3 receptor regulates the release of histamine and a number of other neurotransmitters and thereby plays a role in cognitive and homeostatic processes. Elevated histamine levels suppress seizure activities and appear to confer neuroprotection. The H3 receptors have a number of enigmatic features like constitutive activity, interspecies variation, distinct ligand binding affinities and differential distribution of prototypic splice variants in the CNS. Furthermore, this Gi/Go-protein-coupled receptor modulates several intracellular signalling pathways whose involvement in epilepsy and neurotoxicity are yet to be ascertained and hence represent an attractive target in the search for new anti-epileptogenic drugs. So far, H3 receptor antagonists/inverse agonists have garnered a great deal of interest in view of their promising therapeutic properties in various CNS disorders including epilepsy and related neurotoxicity. However, a number of experiments have yielded opposing effects. This article reviews recent works that have provided evidence for diverse mechanisms of antiepileptic and neuroprotective effects that were observed in various experimental models both in vitro and in vivo. The likely reasons for the apparent disparities arising from the literature are also discussed with the aim of establishing a more reliable basis for the future use of H3 receptor antagonists, thus improving their utility in epilepsy and associated neurotoxicity. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Javed S.,Jamia Hamdard University
Current drug delivery | Year: 2010
From the literature we can draw conclusions regarding the local use of minocycline in periodontal diseases. This review article attempts to evaluate the role of local delivery of minocycline HCl in the management of periodontal diseases. The efficacies of several local delivery devices of minocycline like minocycline films, strips, gels/ointment, microspheres and nanoparticles are discussed. The functional characteristics of local delivery devices of minocycline, their effectiveness as monotherapy, and comparison with scaling and root planning (SRP) are discussed in detail. Methods for the analysis of minocycline in various biological fluids, clinical trials and patents relevant to the local use of minocycline HCl in dental diseases have also been addressed in the article, conceptualizing the fact that direct application of minocycline into the diseased periodontal sulcus is an attractive treatment approach.
Ahmad S.,Jamia Hamdard University
Current clinical pharmacology | Year: 2014
Doxorubicin (DOX) is an effective and frequently used chemotherapeutic agent for various malignancies. However, its clinical use is hampered due to the development of cardiotoxicity. Investigations have proved that DOX-induced cardiotoxicity occurs through mechanisms other than those mediating its antitumor effect. This theory sheds light on the development of strategies for cardioprotection without altering therapeutic effectiveness of DOX. Bioactive plant constituents of dietary supplements, traditional herbs and foods with potential health benefits can play an important role in therapeutics. This manuscript is an exhaustive review and prospect of herbal and botanical agents against DOX-induced cardiotoxicity with their proposed mechanisms. The activity of herbs evaluated against DOX-induced cardiotoxicity has shown number of mechanisms including apoptosis, antioxidant potential, effect on mitochondria and calcium ion regulation etc. The manuscript reveals that most of the herbal drugs studied are effective through antioxidant mechanism and only few through other major pathways such as apoptosis and iron mediated pathways in DOX-induced cardiotoxicity. Only limited reports are available for the prevention of DOX-induced drug resistance using botanicals. Manuscript reports a number of constituents with evident potential in prevention of DOX cardiotoxicity e.g. proanthocyanidins, epigallocatechin-3-gallate, S-allylcysteine, reseveratrol, rutoside etc. In the present communication, several herbal drugs have also been discussed, which can act through mechanisms other than antioxidant and may be evaluated as a combination therapy for prevention of DOX-induced cardiotoxicity in future.
Puranik S.,National Institute of Plant Genome Research |
Puranik S.,Jamia Hamdard University |
Sahu P.P.,National Institute of Plant Genome Research |
Srivastava P.S.,Jamia Hamdard University |
Prasad M.,National Institute of Plant Genome Research
Trends in Plant Science | Year: 2012
The plant-specific NAC (NAM, ATAF1,2 and CUC2) proteins constitute a major transcription factor family renowned for their roles in several developmental programs. Despite their highly conserved DNA-binding domains, their remarkable diversification across plants reflects their numerous functions. Lately, they have received much attention as regulators in various stress signaling pathways which may include interplay of phytohormones. This review summarizes the recent progress in research on NACs highlighting the proteins' potential for engineering stress tolerance against various abiotic and biotic challenges. We discuss regulatory components and targets of NAC proteins in the context of their prospective role for crop improvement strategies via biotechnological intervention. © 2012 Elsevier Ltd.
Jamia Hamdard University and Arbro Pharmaceuticals Ltd. | Date: 2011-04-26
The present invention discloses a pharmaceutical composition in the form of self nano emulsifying drug delivery formulation comprising curcuminoids. The pharmaceutical composition of the present invention shows an enhanced drug loading ability, better stability and an improved bioavailability. The composition of the present invention comprises of a pharmaceutically effective amount of a curcuminoid, an oil phase, a surfactant and a co surfactant.