Abstract:
:Three phenolic glycosides isolated from the heartwood of Pterocarpus marsupium showed significant free radical and superoxide ion scavenging activity and antioxidant potential that were comparable to, or several folds higher than those of standard antioxidants, trolox and ascorbic acid. The effective concentrations of these compounds were far below their cytotoxic levels. Compound 3, which was characterized to be α-dihydroxychalcone-glycoside (α-DHC), was the most potent one. Subsequent studies demonstrated that α-DHC effectively reduced nitric oxide and cytokine production by the LPS stimulated RAW 264.7 mouse macrophage cell line. The compound effectively attenuated the expression of inflammation-mediating enzymes COX-2 and iNOS at the mRNA as well as protein levels in a concentration dependent manner. It prevented phosphorylation of all the three MAPKs (JNK, ERK, p38) and eventually blocked the activation of downstream elements contributing to inflammation. Phosphorylation of IκB-α and subsequent translocation of NF-κB into the nucleus were restricted, while the expression of stress responsive gene HO-1 was up-regulated. α-DHC targeted Keap-1 by modifying its cysteine thiols, dissociating it from Nrf-2 and facilitating nuclear entry of the latter; and this in turn induced HO-1 expression. Thus α-DHC exerts its anti-inflammatory activity in a dual manner: by down regulating MAPKs and restricting nuclear stabilization of NF-κB at one end, and by disrupting Nrf-2-Keap-1 complex on the other. In conclusion, the anti-inflammatory potential together with its high therapeutic index envisages α-DHC as a prospective candidate molecule for the development of therapeutic strategy against inflammatory disorders.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Chakraborty P,Saraswat G,Kabir SNdoi
10.1016/j.taap.2014.03.011subject
Has Abstractpub_date
2014-05-15 00:00:00pages
95-107issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(14)00097-0journal_volume
277pub_type
杂志文章abstract::Heme oxygenase (HO)-1 is an oxidative stress-response enzyme which catalyzes the degradation of heme into bilirubin, ferric ion, and carbon monoxide (CO). Induction of HO-1 was reported to have antitumor activity; the inhibitory mechanism, however, is still unclear. In the present study, we found that treatment with [...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.10.027
更新日期:2014-01-01 00:00:00
abstract::Three novel P450 members of the cytochrome P450 4A family were cloned as partial cDNAs from hamster liver, characterised as novel members of the CYP4A subfamily, and designated CYP4A17, 18, and 19. Hamsters were treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, methylclofenapate (...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2004.01.019
更新日期:2004-05-15 00:00:00
abstract::The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposom...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.09.011
更新日期:2012-11-15 00:00:00
abstract::The primary mechanisms proposed for acetaminophen-induced hepatic necrosis should deplete protein thiols, either by covalent binding and thioether formation or by oxidative reactions such as S-thiolations. However, in previous studies we did not detect significant losses of protein thiol contents in response to admini...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8228
更新日期:1997-10-01 00:00:00
abstract::Pulmonary fibrosis is a consequence of severe injury from some toxic agents including high doses of ozone. It is not known, however, whether chronic exposure to low doses of ozone, such as those encountered in polluted ambient atmospheres, could also result in abnormal accumulations of lung collagen. Rats were exposed...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90184-6
更新日期:1988-03-15 00:00:00
abstract::The disposition of [3H]diisopropylfluorophosphate (DFP) and its metabolites was studied in mice after iv treatment. In addition, disposition of [3H]DFP in selected tissues was correlated with cholinesterase activity and spontaneous activity following DFP treatment. Within 1 min of administration [3H]DFP had penetrated...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90327-8
更新日期:1985-02-01 00:00:00
abstract::The inter-relationship of "Thresholds" between chemical mixtures and their respective component single chemicals was studied using three sets of data and two types of analyses. Two in vitro data sets involve cytotoxicity in human keratinocytes from treatment of metals and a metal mixture [Bae, D.S., Gennings, C., Cart...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2006.11.016
更新日期:2007-09-01 00:00:00
abstract::In the present study the promoting activity of various PCB and PBB isomers and congeners in rat liver has been studied and compared with a variety of primary xenobiotic-mediated enzymatic changes in this target organ. Female Wistar rats were given diethylnitrosamine (DEN; 10 mg/kg body wt for 10 days) and were subsequ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90250-i
更新日期:1991-12-01 00:00:00
abstract::Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxida...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.05.012
更新日期:2009-08-15 00:00:00
abstract::Arsenate (AsV) is a structural analogue of phosphate (P(i)), yet its toxic effect is likely due to its reduction to the more toxic arsenite (AsIII), the mechanism of which is still unclear. Since mitochondria take up AsV as they do P(i), they may reduce AsV to AsIII. To test this hypothesis isolated rat liver mitochon...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2002.9443
更新日期:2002-08-01 00:00:00
abstract::Methyl chloride (MeCl) metabolism and pharmacokinetics were studied in male Fischer 344 rats and male beagle dogs. Apparent steady-state blood MeCl concentrations were proportionate to exposure concentration in rats and dogs exposed to 50 and 1000 ppm. Furthermore, blood MeCl concentrations were similar in both specie...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90292-2
更新日期:1983-05-01 00:00:00
abstract::Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the tre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.07.004
更新日期:2006-04-01 00:00:00
abstract::A quantitative assay based on real-time detection polymerase chain reaction (rtdPCR) was applied to analyze basal and metal-induced mRNA levels of two metallothionein (MT) isoforms (Cd-MT and Cu-MT) in organs of the terrestrial gastropod Helix pomatia. The results show that specific Cd-MT mRNA levels increase with Cd ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(03)00148-0
更新日期:2003-07-01 00:00:00
abstract::Proton magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) have been used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity was seen in the perihilar region of the liver 24 hr after injection of a subl...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90043-e
更新日期:1991-09-15 00:00:00
abstract::Menadione (2-methyl-1,4-naphthoquinone, a redox cycling and arylating quinone; 5-100 microM) inhibited the canalicular vacuolar accumulation (CVA) of a fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), in rat hepatocyte couplets. This was associated with depletion of reduced glutathione and accumulation of oxidiz...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0117
更新日期:1996-06-01 00:00:00
abstract::Acrylonitrile (VCN) is a heavily used monomer in plastic and fiber industries. Quantitatively, VCN-induced gastrointestinal hemorrhage is time and dose dependent and is not the result of a direct irritating action of VCN on gastric tissues. The effect of cytochrome P-450 enzymes inducers was studied. Pretreatment with...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90013-3
更新日期:1983-04-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in female but not in male rats. In an initiation-promotion model, ovariectomy inhibits TCDD-induced cell replication and reduces both TCDD-induced tumor formation and the promotion of enzyme-altered hepatocellular foci (AHF). The aim of this study...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9166
更新日期:2001-05-15 00:00:00
abstract::Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.10.008
更新日期:2012-12-01 00:00:00
abstract::Isoprene (2-methyl-1,3-butadiene), a volatile monomer occurring in the natural environment and used in the manufacture of elastomers, is a close chemical relative of the animal carcinogen 1,3-butadiene. To obtain toxicokinetic data for inhaled isoprene, male F344 rats were exposed in groups of 30 to 14C-labeled isopre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90044-5
更新日期:1987-06-30 00:00:00
abstract::The acute manifestations of experimental bleomycin- and hyperoxia-induced lung damage were examined. Hamsters were treated with 5 U/kg bleomycin intratracheally followed by exposure to 80% oxygen (O2). As little as 12 hr of O2 exposure potentiated the bleomycin injury; however, the onset of mortality was 72 hr after t...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90301-2
更新日期:1987-08-01 00:00:00
abstract::Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible "magic bullet" for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8247
更新日期:1997-11-01 00:00:00
abstract::Although the tricyclic antidepressant drugs imipramine and doxepin exert similar direct electrophysiological effects on cardiac cells, toxic cardiac arrhythmias and conduction disturbances are much more commonly associated with imipramine than doxepin in clinical use. To ascertain if this discrepancy could be due to d...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90143-1
更新日期:1984-06-30 00:00:00
abstract::Previous studies from this laboratory have demonstrated that the addition of methyl groups at the 3 and 4 positions of the 2,5-hexanedione (2,5-HD) molecule results both in more rapid pyrrole formation and in enhanced neurotoxicity. In order to define more clearly the relationship between rates of pyrrole formation an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90296-1
更新日期:1987-02-01 00:00:00
abstract::T-2 toxin, a trichothecene mycotoxin, is a potently cytotoxic and immunosuppressive secondary metabolite produced by Fusarium fungi. Young male white Swiss mice were fed a diet supplemented with T-2 toxin at levels of 5, 10, or 20 ppm, control diet ad libitum, or control diet at a restricted rate for 1, 2, 3, 4, and 6...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90304-6
更新日期:1983-06-30 00:00:00
abstract::1,1-Dichloroethene is used as intermediate in the manufacture of polymers. In male mice, 1,1-dichloroethene caused renal tumors after inhalation. Renal tumors were not observed in female mice or in both sexes of rats. We investigated the metabolic basis for the species- and sex-specific nephrotoxicity and tumorigenici...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1007
更新日期:1995-01-01 00:00:00
abstract::A number of methods have been developed to assess the impact of a xenobiotic on the various components of the immune system. For risk analysis, it is necessary to determine what degree of chemically induced immune perturbation translates into altered host resistance. Natural killer (NK) cells play a pivotal role in th...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9298
更新日期:2001-12-15 00:00:00
abstract::The relative methemoglobin (MetHgb) forming ability of two metabolites of dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), were compared in rat and human whole blood. Concentration-response curves for the two metabolites were generated in vitro in whole blood. Data were fit to ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1255
更新日期:1994-12-01 00:00:00
abstract::Ethyl carbamate (EC) is bioactivated by CYP2E1 through vinyl carbamate to its epoxide, a reactive electrophile. This carcinogen reacts with macromolecules, including hemoglobin (Hb). This report defines a method to examine levels of N-(2-oxoethyl) adduct on the N-terminal valine of Hb after EC treatment at carcinogeni...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1048
更新日期:1995-03-01 00:00:00
abstract::Sexually immature rainbow trout were dosed via gavage with 7,12-[14C]dimethylbenz[a]anthracene (DMBA) in order to study hepatic metabolite formation over time and at single and multiple doses. beta-Glucuronidase and aryl sulfatase hydrolyses of bile extracts and subsequent high-pressure liquid chromatography analysis ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1129
更新日期:1993-07-01 00:00:00
abstract::A physiologically based pharmacokinetic (PBPK) model describing transfer of inhaled tetrachloroethylene (PCE) into breast milk with the consequent exposure of the nursing pups was developed and validated in lactating rats. The PBPK model was based on partition coefficients (PCs), which were determined by the equilibra...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1068
更新日期:1994-04-01 00:00:00