National Toxicology Center

Pune, India

National Toxicology Center

Pune, India

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Chaphalkar R.,Narsee Monjee Institute of Management and Higher Studies | Apte K.G.,National Toxicology Center | Talekar Y.,National Toxicology Center | Ojha S.K.,United Arab Emirates University | Nandave M.,Narsee Monjee Institute of Management and Higher Studies
Oxidative Medicine and Cellular Longevity | Year: 2017

Phyllanthus emblica L. (amla) has been used in Ayurveda as a potent rasayan for treatment of hepatic disorders. Most of the pharmacological studies, however, are largely focused on PE fruit, while the rest of the parts of PE, particularly, bark, remain underinvestigated. Therefore, we aimed to investigate the protective effect of the hydroalcoholic extract of Phyllanthus emblica bark (PEE) in ethanol-induced hepatotoxicity model in rats. Total phenolic, flavonoid, and tannin content and in vitro antioxidant activities were determined by using H2O2 scavenging and ABTS decolorization assays. Our results showed that PEE was rich in total phenols (99.523±1.91 mg GAE/g), total flavonoids (389.33±1.25 mg quercetin hydrate/g), and total tannins (310±0.21 mg catechin/g), which clearly support its strong antioxidant potential. HPTLC-based quantitative analysis revealed the presence of the potent antioxidants gallic acid (25.05 mg/g) and ellagic acid (13.31 mg/g). Moreover, one-month PEE treatment (500 and 1000 mg/kg, p.o.) followed by 30-day 70% ethanol (10 mL/kg) administration showed hepatoprotection as evidenced by significant restoration of ALT (p<0.01), AST (p<0.001), ALP (p<0.05), and TP (p<0.001) and further confirmed by liver histopathology. PEE-mediated hepatoprotection could be due to its free radical scavenging and antioxidant activity that may be ascribed to its antioxidant components, namely, ellagic acid and gallic acid. Thus, the results of the present study support the therapeutic claims made in Ayurveda about Phyllanthus emblica. © 2017 Renuka Chaphalkar et al.

Puranik A.S.,University of Pune | Halade G.,University of Texas Health Science Center at San Antonio | Kumar S.,National Center for Cell science | Mogre R.,Applied Biotech Vile Parle | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2011

Safety pharmacology studies help in identifying preclinical adverse drug reactions. We carried out routine safety pharmacology with focus on cardiovascular variables and pharmacokinetic herb-drug interaction studies on rats fed with standardized traditional hydro-alcoholic extract and technology-based supercritical extract of Cassia auriculata for 12 weeks. Our studies indicate that both these extracts are pharmacologically safe and did not show any significant adverse reactions at the tested doses. The traditional hydro-alcoholic extract did not show any significant effect on pharmacokinetics; however, the technology-based supercritical extract caused a significant reduction in absorption of metformin. Our results indicate the need to include pharmacokinetic herb-drug interaction studies as evidence for safety especially for technology-based extracts. Copyright 2011 Amrutesh S. Puranik et al.

Rosano T.G.,Albany Medical College | Rosano T.G.,National Toxicology Center | Ohouo P.Y.,National Toxicology Center | LeQue J.J.,National Toxicology Center | And 2 more authors.
Journal of Analytical Toxicology | Year: 2016

Drug screening is an essential analytical tool for detection of therapeutic, illicit and emerging drug use. Presumptive immunoassay screening is widely used, while initial definitive testing by chromatography-coupled mass spectrometry is hampered due to complex pre-analysis steps, long chromatography time and matrix effects. The aim of this study is to develop and validate a definitive test for rapid and threshold accurate screening of 33 drugs or metabolites (analytes) in urine. Sample preparation in a 96-well plate format involves rapid glucuronidase hydrolysis followed by dilution, filtration and ultra-performance liquid chromatography-MS-MS analysis. Chromatographic separation, on an ACQUITY UPLC® BEH phenyl column is optimized for a 3-min MS-MS ion acquisition. Matrix effect was normalized by an innovative technique called threshold accurate calibration employing an additional analysis with an analyte spike as an internal standard undergoing the same matrix effect as an analyte in a drug-positive donor specimen. Accuracy and precision, at above and below threshold concentrations, were determined by replicate analysis of control urine pools containing 50, 75, 125 and 150% of threshold concentrations. Accuracy and selectivity were further demonstrated by concordant findings in proficiency and confirmatory testing. The study shows the applicability of definitive testing as an alternative to immunoassay screening and demonstrates a new approach to normalization of matrix effect. © The Author 2016. Published by Oxford University Press. All rights reserved.

PubMed | Waters Corporation, National Toxicology Center and Albany Medical College
Type: Journal Article | Journal: Journal of analytical toxicology | Year: 2016

Drug screening is an essential analytical tool for detection of therapeutic, illicit and emerging drug use. Presumptive immunoassay screening is widely used, while initial definitive testing by chromatography-coupled mass spectrometry is hampered due to complex pre-analysis steps, long chromatography time and matrix effects. The aim of this study is to develop and validate a definitive test for rapid and thresholdaccurate screening of 33 drugs or metabolites (analytes) in urine. Sample preparation in a 96-well plate format involves rapid glucuronidase hydrolysis followed by dilution, filtration and ultra-performance liquid chromatography-MS-MS analysis. Chromatographic separation, on an ACQUITY UPLC

Ameri A.,Ahvaz Jundishapur University of Medical Sciences | Rajive B.B.,Armed Force Medical College Dalanwala | Vaidya J.G.,University of Pune | Apte K.,National Toxicology Center | Deokule S.S.,University of Pune
International Journal of Applied Research in Natural Products | Year: 2013

Topical antimicrobial therapy is one of the most important methods of wound care. In this investigation, we evaluated topical gel preparations of Ganoderma praelongum and Glycyrrhiza glabra aqueous extracts alone and in combination for antimicrobial and wound healing activities in MRSA - infected excision and incision wound models in mice. Gel formulations containing 0.3% G. praelongum, 2.5% G. glabra and combination of the two were prepared and tested for their influence on wound infection, wound contraction and epithelization phases of wound healing. Mupirocin ointment was applied as a standard treatment antibiotic. Results indicated that all three gel formulations promoted wound healing in both models by influencing wound contraction and epithelization phases. Examination of wounds at the end of our study period revealed that wounds treated with G. praelongum and G. glabra gel formulations (combination gel) showed considerable contraction and epithelization as compared to the gel base - treated group (negative control). Assumption could be made that this wound promotion is due to the anti - Staphylococcal activity of Ganoderma and wound healing activity of G. glabra. Industrial relevance. Medicine using fungal metabolites is now recognized. A mushroom that has gained worldwide attention is Ganoderma lucidum and has been used to treat a wide spectrum of ailments including fungal and bacterial infections for long periods of time throughout history of ancient traditional medicine. Previous reports indicate that ganoderma lucidum mycelia are usually prescribed in the form of soup, syrup, tea, tablets, capsules, tincture or bolus or injected as a solution of powdered spores.In this study, the combination gel containing aqueous extracts of G. praelongum and G. glabra effectively inhibited the growth of methicillin resistant Staphylococcus aureus and promoted wound healing in mice. Further phytochemical studies are needed to pinpoint the active components of the extracts. Moreover, various topical formulations containing combination of the two extracts are suggested to be prepared and evaluated for wound healing in clinical trials. © 2008-2013. IJARNP-HS Publication.

Hardikar A.A.,University of Sydney | Satoor S.N.,University of Sydney | Satoor S.N.,National Center for Cell Science | Karandikar M.S.,DY Patil Medical College | And 20 more authors.
Cell Metabolism | Year: 2015

People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations. © 2015 Elsevier Inc.

Banerjee A.G.,Banaras Hindu University | Das N.,Banaras Hindu University | Das N.,Assam University | Shengule S.A.,National Toxicology Center | And 3 more authors.
Bioorganic Chemistry | Year: 2016

A series of novel hybrids comprising of 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole tethered to 5,6-diphenyl-1,2,4-triazin-3(2H)-one were designed, synthesised and evaluated as COX-2 inhibitors for the treatment of inflammation. The synthesised hybrids were characterised using FT-IR, 1H NMR, 13C NMR, elemental (C,H,N) analyses and assessed for their anti-inflammatory potential by in vitro albumin denaturation assay. Compounds exhibiting activity comparable to indomethacin and celecoxib were further evaluated for in vivo anti-inflammatory activity. Oral administration of promising compounds 3c–3e and 4c–4e did not evoke significant gastric, hepatic and renal toxicity in rats. These potential compounds exhibited reduced malondialdehyde (MDA) content on the gastric mucosa suggesting their protective effects by inhibition of lipid peroxidation. Based on the outcome of in vitro COX assay, compounds 3c–3e and 4c–4e (IC50 0.60–1.11 μM) elicited an interesting profile as competitive selective COX-2 inhibitors. Further, selected compounds 3e and 4c were found devoid of cardiotoxicity post evaluation on myocardial infarcted rats. The in silico binding mode of the potential compounds into the COX-2 active site through docking and molecular dynamics exemplified their consensual interaction and subsequent COX-2 inhibition with significant implications for structure-based drug design. © 2016 Elsevier Inc.

Makadiya V.S.,Maharashtra Institute of Pharmacy | Kulkarni Y.A.,Maharashtra Institute of Pharmacy | Apte K.G.,National Toxicology Center
Journal of Herbs, Spices and Medicinal Plants | Year: 2015

Toxicity of aqueous extract (AE) of stem bark of Bauhinia variegata was evaluated. In the acute toxicity study, Sprague-Dawley rats were treated orally with AE (2,000 or 5,000 b.w). The animal behavior and mortality were observed periodically for up to 14 d. In the repeated dose toxicity study, the AE was administered daily at doses of 1,000 or 2,000 b.w, for 28 d. Behavior and mortality of animals were observed during the test period and hematological, biochemical parameters and histopathological examinations were carried out. In acute toxicity study, AE did not produce any mortality, changes in behavior, or any other physiological activities in rats at all selected doses. In repeated dose toxicity study, the monocytes and lymphocytes decreased at high doses. AE did not affect the biochemical parameters (except glucose) and the organs weight. Histopathology studies revealed no changes in cellular structure of the organs studied. The AE of B. variegata had maximally tolerated dose (MTD) of 5,000 in acute toxicity study and lowest observed adverse effect level of 1,000 in repeated-dose toxicity study in rats. © Taylor & Francis Group, LLC.

Sonawane H.B.,University of Pune | Ghole V.S.,University of Pune | Garad S.,University of Pune | Bapat G.,University of Pune | And 2 more authors.
Journal of Natural Remedies | Year: 2013

Phansomba (Phellinus badius Berk ex Cooke) G. Cunn., family Hymenochetaceae, is a folk medicine used by local practitioners for various types of ailments. The hypoglycemic effect of aqueous extract of fruit body and mycelial biomass were investi gated in alloxan-induced diabetic rats. The diabeticrats were orally administered with aqueous extracts of Phellinus badius, basidiocarp, and mycelial biomass at the doses of 800 mg/kg and 1000 mg/kg each. The blood glucose level changed at 6-hr interval at a dose of 1000 mg/kg in case of basidiocarp and mycelial biomass. The food intake of diabetic control was increased by 33.6% as compared to normal control, and the body weight gain was significantly decreased at a dose of 1000 mg/kg of both the samples. The blood glucose levels of the diabetic rats were significantly reduced after fourteen days. The plasma triglyceride and cholesterol level also significantly decreased as compared to diabetic rats (positive control). There was a considerable increase in the weight of body organs on administration of aqueous extract of Phansomba sample as compared to the normal rats (negative control). It also demonstrated a marked reduction in the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The study reveals the potential of Phansomba samples as hypoglycemic agents with its aqueous extracts from fruit body and mycelial biomass.

Banerjee A.G.,Banaras Hindu University | Das N.,Banaras Hindu University | Shengule S.A.,National Toxicology Center | Srivastava R.S.,Banaras Hindu University | Shrivastava S.K.,Banaras Hindu University
European Journal of Medicinal Chemistry | Year: 2015

A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in acute, sub-chronic and chronic animal models of inflammation. Derivatives 4d, 4e, 4g, 4j and 4l exhibited significant anti-inflammatory activity with reduced ulcerogenic, hepatotoxic and renotoxic liabilities compared to standard indomethacin. These potential derivatives were also evaluated for in vivo analgesic activity using a writhing model and the formalin-induced paw licking response in mice. Compounds 4d, 4e and 4g exhibited comparable analgesic activity, whereas 4j and 4l yielded moderate effects. The specificity of compounds 4d, 4e, 4g, 4j, and 4l to inhibit (cyclooxygenase-1) COX-1 and (cyclooxygenase-2) COX-2 isozymes and their kinetics were also determined via an in vitro COX inhibition assay. In silico docking studies were performed using a molecular dynamics simulation of the most active compound 4d (COX-2 IC50: 3.07 μM) at the COX-2 active site. The outcome of this exercise helped to verify the consensual interaction of these compounds with the enzyme. © 2015 Elsevier Masson SAS.

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