Bharat Institute of Technology

Meerut, India

Bharat Institute of Technology

Meerut, India

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Yadav R.K.,Meerut Institute of Engineering and Technology | Gupta S.P.,Meerut Institute of Engineering and Technology | Sharma P.K.,Meerut Institute of Engineering and Technology | Patil V.M.,Bharat Institute of Technology
Current Medicinal Chemistry | Year: 2011

Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc- containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan. The inappropriate expression of these MMPs constitutes part of the pathogenic mechanism in several diseases, therefore they are subject to inhibition. They can be inhibited by endogenous proteinase inhibitors such as 2-macroglobulin or by the family of tissue inhibitors of metalloproteinases (TIMPs), which are glycoproteins of molecular weight 21-30 kDa, consisting of 184- 194 amino acid residues. Recently, many different classes of synthetic inhibitors have been developed in which the hydroxamic acidbased class of compounds (hydroxamates) have been most widely studied, as their hydroxamic acid group (CONHOH) enables them to act as a bidentate ligand with the zinc ion present in MMPs, leading to much stronger interaction with the receptor as compared to any other class of inhibitors. The present review describes in detail the recent development on this class of MMP inihibitors. Compounds like 12,17e, f, g and h, 45j, 45k, 50f, 62a, 63a, and 63b have been reported to be highly promising for further development. © 2011 Bentham Science Publishers Ltd.


Sharma B.,Punjabi University | Sharma B.,Bharat Institute of Technology | Singh N.,Punjabi University
Pharmacology Biochemistry and Behavior | Year: 2013

Cognitive disorders are likely to increase over the coming years (5-10). Vascular dementia (VaD) has heterogeneous pathology and is a challenge for clinicians. Current Alzheimer's disease drugs have had limited clinical efficacy in treating VaD and none have been approved by major regulatory authorities specifically for this disease. Role of iNOS and NADPH-oxidase has been reported in various pathological conditions but there role in hypertension (Hypt) induced VaD is still unclear. This research work investigates the salutiferous effect of aminoguanidine (AG), an iNOS inhibitor and 4′-hydroxy-3′- methoxyacetophenone (HMAP), a NADPH oxidase inhibitor in Hypt induced VaD in rats. Deoxycorticosterone acetate-salt (DOCA-S) hypertension has been used for development of VaD in rats. Morris water-maze was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Mean arterial blood pressure (MABP), oxidative stress [aortic superoxide anion, serum and brain thiobarbituric acid reactive species (TBARS) and brain glutathione (GSH)], nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity-AChE) were also measured. DOCA-S treated rats have shown increased MABP with impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate & brain GSH levels along with increase in serum & brain TBARS, and brain AChE activity. AG as well as HMAP significantly convalesce Hypt induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that AG, an iNOS inhibitor and HMAP, a NADPH-oxidase inhibitor may be considered as potential agents for the management of Hypt induced VaD. © 2012 Elsevier Inc.


Singh P.,Bharat Institute of Technology | Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
Physiology and Behavior | Year: 2015

Cerebrovascular and cardiovascular diseases are stated as important risk factors of vascular dementia (VaD) and other cognitive disorders. In the central nervous system, melatonin (MT1/MT2) as well as serotonin subtype 2C (5-HT2C) receptors is pharmacologically associated with various neurological disorders. Brain mitochondrial potassium channels have been reported for their role in neuroprotection. This study has been structured to investigate the role of agomelatine, a melatonergic MT1/MT2 agonist and nicorandil, a selective ATP sensitive potassium (KATP) channel opener in renal artery ligation (two-kidney-one-clip: 2K1C) hypertension induced endothelial dysfunction, brain damage and VaD. 2K1C-renovascular hypertension has increased mean arterial blood pressure (MABP), impaired memory (elevated plus maze and Morris water maze), endothelial function, reduced serum nitrite/nitrate and increased brain damage (TTC staining of brain sections). Furthermore, 2K1C animals have shown high levels of oxidative stress in serum (increased thiobarbituric acid reactive species-TBARS with decreased levels of glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), in the aorta (increased aortic superoxide anion) and in the brain (increased TBARS with decreased GSH, SOD and CAT). 2K1C has also induced a significant increase in brain inflammation (myeloperoxidase-MPO levels), acetylcholinesterase activity (AChE) and calcium levels. Impairment in mitochondrial complexes like NADH dehydrogenase (complex-I), succinate dehydrogenase (complex-II) and cytochrome oxidase (complex-IV) was also noted in 2K1C animals. Administration of agomelatine, nicorandil and donepezil significantly attenuated 2K1C-hypertension induced impairments in memory, endothelial function, nitrosative stress, mitochondrial dysfunction, inflammation and brain damage. Therefore, modulators of MT1/MT2 receptors and KATP channels may be considered as potential agents for the management of renovascular hypertension induced VaD. © 2015 Elsevier Inc.


Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
Pharmacology Biochemistry and Behavior | Year: 2014

Huntington's disease (HD), a devastating neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss, depression. Melatonin receptors are widely expressed in the central nervous system. Vanilloids are also valuable as pharmacological tools for investigating neurobiology. This study investigates the utility of agomelatine, a dual agonist of MT1 and MT2 melatonin receptor as well as vanillin, a selective agonist of TRPV1 (vanilloid receptor) in 3-nitropropionic acid (3-NPA) induced experimental HD in rats. Locomotor activity (Actophotometer), motor coordination (Rota rod) and learning-memory (Morris water maze) were assessed. Brain striatum oxidative stress (lipid peroxidation-MDA, glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), nitrosative stress (nitrite/nitrate) and mitochondrial enzyme complexes (I, II and IV) were also assessed. 3-NPA has induced weight loss, impaired locomotion, motor coordination as well as learning and memory. It has induced brain striatum oxidative as well as nitrosative stress, cholinergic dysfunction and impaired mitochondrial enzyme complexes (I, II and IV). Tetrabenazine (TBZ) was used as positive control. Treatment with agomelatine and vanillin and TBZ has significantly attenuated 3-NPA induced weight loss, impaired locomotion, motor coordination and learning-memory as well as biochemical impairments. Thus, agomelatine and vanillin exhibit protective effects against 3-NPA induced HD. It may be concluded that agomelatine and vanillin may provide benefits in HD. © 2014 Elsevier Inc.


Gupta S.,Neuropharmacology Laboratory | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
European Journal of Pharmacology | Year: 2014

Huntingtons disease (HD), a devastating neurodegenerative disorder, is characterized by weight loss, impairment of motor function, cognitive dysfunction, neuropsychiatric disturbances and striatal damage. Phosphodiesterase-1 (PDE1) has been implicated in various neurological diseases. Mitochondrial potassium channels in the brain take part in neuroprotection. This study has been structured to investigate the role of vinpocetine, a selective PDE1 inhibitor as well as nicorandil, selective ATP sensitive potassium (KATP) channel opener in 3-nitropropionic acid (3-NP) induced HD symptoms in rats. Systemic administration of 3-NP significantly, reduced body weight, impaired locomotion, grip strength and impaired cognition. 3-NP elicited marked oxidative stress in the brain (enhanced malondialdehyde-MDA, reduced glutathione-GSH content, superoxide dismutase-SOD and catalase-CAT), elevated brain acetylcholinesterase activity and inflammation (myeloperoxidase-MPO), with marked nitrosative stress (nitrite/nitrate) in the brain. 3-NP has also induced mitochondrial dysfunction (impaired mitochondrial NADH dehydrogenase-complex I, succinate dehydrogenase-complex II and cytochrome oxidase-complex IV) activities in the striatum of the rat. Tetrabenazine was used as a positive control. Treatment with vinpocetine, nicorandil and tetrabenazine ameliorated 3-NP induced reduction in body weight, impaired locomotion, grip strength and impaired cognition. Treatment with these drugs reduced brain striatum oxidative (MDA, GSH, SOD and CAT) and nitrosative (nitrite/nitrate) stress, acetylcholinesterase activity, inflammation and mitochondrial dysfunctions. These results indicate that vinpocetine, a selective PDE1 inhibitor and nicorandil, a K ATP channel opener have attenuated 3-NP induced experimental HD. Hence, pharmacological modulation of PDE1 as well as KATP channels may be considered as potential research targets for mitigation of HD. © 2014 Elsevier B.V.


Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
Brain Research Bulletin | Year: 2014

Huntington's disease (HD), a neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss and anxiety.The tremendous amount of research work is required to identify new pharmacological agents of therapeutic utility to combat this condition. This study investigates the effect of selective modulator of I1-imidazoline receptor (moxonidine) as well as nuclear factor kappa-B (NF-κB) (natrium diethyl dithio carbamate trihydrate-NDDCT) on 3-nitropropionic acid (3-NPA) induced experimental HD condition. 3-NPA was used to induce mitochondrial damage and associated HD symptoms in rats. Anxiety was assessed using Elevated plus maze-EPM and learning-memory was assessed using EPM and Morris water maze-MWM. Different biochemical estimations were used to assess brain striatum oxidative stress (lipid peroxide, superoxide dismutase and catalase), nitric oxide levels (nitrite/nitrate), cholinergic activity (brain striatum acetyl cholinesterase activity), and mitochondrial enzyme complex (I, II and IV) activities. 3-NPA has induced anxiety, impaired learning-memory with a reduction in body weight, locomotor activity, grip strength. It has increased brain striatum acetylcholinesterase-AChE activity, oxidative stress (lipid peroxide, nitrite/nitrate, superoxide dismutase and catalase) and impaired mitochondrial complex enzyme (I, II and IV) activities. Tetrabenazine-TBZ (monoamine storage inhibitor) was used as positive control. Treatment with moxonidine, NDDCT and TBZ significantly attenuated 3-NPA induced reduction in body weight, locomotor activity, grip strength, anxiety as well as impaired learning and memory. Administration of these agents attenuated 3-NPA induced various biochemical impairments. Therefore, modulation of I1-imidazoline receptor as well as NF-κB may be considered as potential pharmacological agents for the management of 3-NPA induced HD. © 2014 Elsevier Inc.


Singh P.,Neuropharmacology Laboratory | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research | Gupta S.,Neuropharmacology Laboratory | Sharma B.M.,Bharat Institute of Technology
Psychopharmacology | Year: 2015

Rationale: Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Objective Present study has been structured to investigate the role of insulin and pharmacological modulator of KAT P channel (gliclazide) in experimental morphine withdrawal syndrome, both in vivo and in vitro. Methods: In this study, naloxone-precipitated morphine withdrawal syndrome in mice (in vivo) as well as in rat ileum (in vitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca+2) were assessed. Results: Naloxone has significantly increased morphine withdrawal syndrome, both in vivo and in vitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, fore-paw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca+2 in morphine-dependent animals (in vivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Conclusions: Insulin and gliclazide (KAT P channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both in vivo and in vitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal. © 2014 Springer-Verlag Berlin Heidelberg.


Patil V.M.,Bharat Institute of Technology
EXS | Year: 2012

Matrix metalloproteinases (MMPs) regulate a wide range of biological functions, but their overactivation leads to a wide array of disease processes such as rheumatoid arthritis, ostereoarthritis, tumor metastatis, multiple sclerosis, congestive heart failure, and a host of others. Therefore, the study of MMP inhibitors has evoked a great interest among scientists. As a result, different groups of compounds have been synthesized and studied for MMP inhibitions. Among them, a large number of structurally novel sulfonamide derivatives have been reported to be potential MMP inhibitors, but only a few have reached to the final stage of clinical trial. Many authors have made quantitative structure-activity relationship (QSAR) studies on them to provide the guidelines to design more potent MMP inhibitors. This article presents a comprehensive review on all such QSARs reported with critical assessment in order to provide a deeper insight into the structure-activity relationship of sulfonamides which can be used to synthesize highly potential drugs of pharmaceutical importance.


Verma N.,Bharat Institute of Technology | Khosa R.L.,Bharat Institute of Technology
Indian Journal of Biochemistry and Biophysics | Year: 2010

Zanthoxylum armatum DC (Rutaceae) is extensively used in indigenous system of medicine as a tonic, carminative, stomachic and anthelmintic. In the present study, the hepatoprotective activity of the leaves ethanolic extract of Z. armatum (EEZA) was evaluated in CCl4-induced hepatotoxicity in rats. The extract at a dose of 500 mg/kg registered a significant decrease in the levels of serum glutamyl oxalacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaline phosphatase (ALKP), and serum bilurubin (SBLN) and liver inflammation, which was supported by histopathological studies on liver, thus exhibited a significant hepatoprotective activity. The phytochemical screening of defatted ethanolic extract showed the presence of sterols, alkaloids, flavonoids, and reducing sugars.


Tiwari B.K.,Translam Institute of Pharmaceutical Education and Research | Khosa R.L.,Bharat Institute of Technology
Internet Journal of Tropical Medicine | Year: 2010

The flower heads of Sphaeranthus indicus Linn (Asteraceae) a traditional Indian medicinal plant is commonly used to nourish and improve the liver conditions. This study was designed to evaluate the hepatoprotective and antioxidant effect of aqueous (AQS) and methanolic (MES) extract of flower heads of Sphaeranthus indicus on Paracetamol (APAP)-induced hepatotoxicity in rat's in-vivo. Activities of liver marker enzymes, glutamate-oxaloacetate transaminase (SGOT) glutamate pyruvate transaminase (SGPT), acid phosphatase (ACP) and alkaline phosphatase (ALP) bilirubin and total protein at an oral dose of MES (300mg/kg) showed a significant hepatoprotective effect in comparison with the same dose of aqueous extract. This fact was also confirmed by studying the liver histopathology of treated animals. As Regards the antioxidant activity, MES exhibited a significant effect (P < 0.05) showing increasing levels of superoxide dismutase (SOD), Catalase (CAT), and glutathione peroxides (GPX) by reducing malondialdehyde (MDA) levels. © Internet Scientific Publications, LLC., 1996 to 2010.

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