Abstract:
:Acute respiratory distress syndrome threatens public health with high morbidity and mortality due to ineffective intervention whereby lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice provides a research model. The seeds of Euphorbia lathyris L. have a long history of usage in Traditional Chinese Medicine. Euphorbia factors L1-L11, extracted from this herb, have been reported to have anti-inflammation and anti-cancer effects. Here, we report the preventive and therapeutic potential of Euphorbia factor L2 (EFL2) on LPS-induced ALI in mice, where EFL2 attenuated pathological alterations in the lung and improved survival. Significant suppression of the recruitment and transmigration of inflammatory cells, specifically neutrophils, by 40 mg/kg of EFL2 was observed. EFL2 exerted potent anti-inflammatory effects by decreasing the levels of interleukin-1β (IL-1 β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), interleukin-8 (IL-8) and myeloperoxidase (MPO) in the lung and bronchioalveolar lavage fluid. Consistent with the findings in vivo, EFL2 also showed robust inhibitory effects on the production of IL-1 β, IL-6, TNF- α and IL-8 released from LPS-stimulated RAW264.7 cells in vitro. Interestingly, this effect appeared to be mediated by EFL2's inhibition of NF-κB signaling activation, but not the MAPK pathway. Not only phosphorylation of IKK α/β and IκBα was down-regulated, p65 translocation and its DNA-binding activity were also significantly suppressed by EFL2. Moreover, overexpression of p65 reversed the inhibitory effect of EFL2 in LPS-induced NF-κB activation and cytokines production. The observed anti-inflammatory bioactivity of EFL2 indicates its potential as a drug development candidate, particularly for LPS-mediated disorders of inflammation.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Zhang Q,Zhu S,Cheng X,Lu C,Tao W,Zhang Y,William BC,Cao X,Yi S,Liu Y,Zhao Y,Luo Ydoi
10.1016/j.bcp.2018.07.025subject
Has Abstractpub_date
2018-09-01 00:00:00pages
444-454eissn
0006-2952issn
1873-2968pii
S0006-2952(18)30293-4journal_volume
155pub_type
杂志文章abstract::The antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has been shown previously to be enhanced markedly by the co-administration of pyrimidine deoxyribonucleosides (Lin and Prusoff, Cancer Res 47: 394-397, 1987). In the present study, we examined the cellular mechanisms underlying the augmentation effe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00905-7
更新日期:1997-03-07 00:00:00
abstract::Sodium nitroprusside (SNP) stimulates cGMP formation to a greater extent in 20,000 g supernatant fractions of the human neuroblastoma clones NB1-G and SH-SY5Y than in the human astrocytoma clone D384. This suggests that these cell lines contain the soluble form of guanylate cyclase. Arachidonic, 8,11,14- and 11,14,17-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90069-w
更新日期:1990-02-01 00:00:00
abstract::In order to understand the relationship between the free ionized calcium concentration in the axon terminals and the transmitter release we have investigated the effect of ruthenium red (RuR) and m-chloro-carbonylcyanide phenyl hydrazon (CCCP), mitochondrial uncoupler agents on the liberation of acetylcholine from mye...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90020-7
更新日期:1987-11-01 00:00:00
abstract::MOLT-4 (T-), RAJI (B-), and KM-3 (non-B-non-T-, common ALL) malignant lymphoblasts demonstrated significant differences in their activities of purine de novo synthesis (PDNS) and purine salvage pathway and in their cell-kinetic parameters. Incubations with concentrations of methotrexate (0.02 and 0.2 microM), which ca...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90359-0
更新日期:1988-06-15 00:00:00
abstract::Ciprofibrate (CP), a peroxisome proliferator, has been shown to reduce rat liver endoplasmic reticulum (ER) Ca(2+)-ATPase activity both in vitro and in vivo. The ER Ca(2+)-ATPase is highly susceptible to thiol reactivity, and maintenance of maximal enzyme activity is critically dependent upon the integrity of these th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90021-n
更新日期:1993-05-25 00:00:00
abstract::Rat liver microsomes and purified NADPH-cytochrome c reductase metabolized [14C]misonidazole anaerobically to a reactive intermediate that covalently binds to tissue macromolecules. Air strongly inhibited the binding whereas carbon monoxide had no effect, indicating that misonidazole is activated via reduction and not...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90158-7
更新日期:1982-02-15 00:00:00
abstract::Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanate...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.03.044
更新日期:2004-09-15 00:00:00
abstract::As a group, the carcinomas represent a substantial proportion of all human malignancies, but, with relatively few exceptions, current treatments are ineffective. Modification of existing chemotherapeutic agents has not led to significant improvements in the survival of carcinoma patients, and development of new therap...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/0006-2952(95)02232-5
更新日期:1996-05-03 00:00:00
abstract::The DNA-topoisomerase I (Topo I) inhibitor, camptothecin (CPT), is a plant alkaloid with an important antitumor activity. In order to investigate the cellular mechanism leading to the development of the resistance to this agent, we have established by progressive adaptation a P388 subline resistant to CPT. After 5 mon...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90069-9
更新日期:1993-01-26 00:00:00
abstract::Imaging the pharmacodynamics of anti-cancer drugs may allow early assessment of anti-cancer effects. Increases in 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake early after thymidylate synthase inhibition (TS) inhibition, the so-called flare response, is considered to be largely due to an increase in binding s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.08.004
更新日期:2010-11-15 00:00:00
abstract::Several derivatives of N-t-butyl-alpha-phenylnitrone (PBN) such as N-2-(2-ethoxycarbonyl-propyl)-alpha-phenylnitrone (EPPN) have recently been reported to form superoxide spin adducts (t(1/2) ca. 2-7 min at pH 7.0), which are considerably more stable than their respective PBN or DMPO adducts (t(1/2) ca. 10 and 45 s, r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.03.017
更新日期:2004-07-01 00:00:00
abstract::The cellular distribution of cytochrome P-450 has been studied in the liver and a number of extrahepatic tissues in the rat by immunocytochemistry, using an antibody raised against cytochrome P-450 form c. Immunoreactive cytochrome P-450, most probably form c, was found in the proximal tubules of the kidney, in the Cl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90777-x
更新日期:1986-12-15 00:00:00
abstract::Studies have been carried out to analyze the phosphoprotein composition of plasma membranes from Chinese hamster lung cells resistant to the action of adriamycin. Gel electrophoretic analysis of [32Pi]-labeled proteins revealed that plasma membranes from resistant cells contain a phosphoprotein of 180,000 molecular we...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90315-5
更新日期:1983-12-01 00:00:00
abstract::JG-03-14, a substituted pyrrole that inhibits microtubule polymerization, was screened against MCF-7 (p53 wild type), MDA-MB231 (p53 mutant), MCF-7/caspase 3 and MCF-7/ADR (multidrug resistant) breast tumor cell lines. Cell viability and growth inhibition were assessed by the crystal violet dye assay. Apoptosis was ev...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.07.003
更新日期:2007-10-01 00:00:00
abstract::Phosphatidylinositol specific phospholipase C from Staphylococcus aureus could solubilize acetylcholinesterase up to 55% from sheep platelets in the presence of ethylenediaminetetra acetic acid (EDTA). The endogenous phosphatidylinositol specific phospholipase C of platelets activated by deoxycholate (at 3-5 mM) could...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90202-3
更新日期:1985-12-01 00:00:00
abstract::The multidrug resistance (MDR) phenotype is the major cause of failure of cancer chemotherapy. This phenotype is mainly due to the overexpression of the human MDR1 (hMDR1) gene. Several studies have shown that transcriptional regulation of this gene is unexpectedly complex and is far from being completely understood. ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(02)01156-5
更新日期:2002-09-01 00:00:00
abstract::The underlying mechanism of the antiproliferative effect of S (simvastatin), a HMG-CoA reductase inhibitor, in vascular smooth muscle cells (SMC) is still poorly understood. In the present study, we used synchronized human SMC, isolated from left interior mammary artery, as an in vitro model to test the effects of S o...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00566-4
更新日期:2001-04-15 00:00:00
abstract::Triethylamine, which was used as an elution solvent for column chromatography to purify chemically synthesized 3'-phosphoadenosine 5'-phosphosulfate (PAPS), was a potent inhibitor of rat liver sulfotransferase (ST) activities toward androsterone and dehydroepiandrosterone, but not ST activities toward cortisol and 2-n...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90523-y
更新日期:1993-08-03 00:00:00
abstract::Histrionicotoxin, a spiropiperidine alkaloid, and twenty-two analogs inhibited binding of [3H]perhydrohistrionicotoxin [( 3H]H12-HTX) and of [3H]phencyclidine [( 3H]PCP) to sites on the acetylcholine receptor-ion complex of Torpedo electroplax membranes. Structural alterations to the nitrogen (secondary amine) or oxyg...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90145-5
更新日期:1985-09-01 00:00:00
abstract::Phentermine was shown in the 1970s to inhibit the metabolism of serotonin by monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence, it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. We examined the effe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00306-3
更新日期:2000-06-15 00:00:00
abstract::The role of CYP2E1 in ketone-stimulated insulin release was investigated using isolated pancreatic islets of Langerhans and two mammalian insulin secreting pancreatic beta-cell lines engineered to stably express human CYP2E1 (designated BRIN BD11h2E1 and INS-1h2E1). Isolated rat pancreatic islets were shown to express...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.10.011
更新日期:2004-03-01 00:00:00
abstract::Platelet secretion is an important physiological event in hemostasis. The protease-activated receptors, PAR 1 and PAR 4, and the thromboxane receptor activate the G(12/13) pathways, in addition to the G(q) pathways. Here, we investigated the contribution of G(12/13) pathways to platelet dense granule release. 2MeSADP,...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.11.017
更新日期:2009-03-01 00:00:00
abstract::Phospho-tyrosol-indomethacin (PTI; MPI 621), a novel anti-cancer agent, is more potent and safer than conventional indomethacin. Here, we show that PTI was extensively metabolized in vitro and in vivo. PTI was rapidly hydrolyzed by carboxylesterases to generate indomethacin as its major metabolite in the liver microso...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.01.031
更新日期:2013-04-15 00:00:00
abstract::Hypertension is considered as one of the cancer progressive factors, and often found comorbidity in cancer patients. Renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, and angiotensin II (Ang II) is well known pressor peptide associated with RAS. Ang II has been reported to acc...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.04.012
更新日期:2018-08-01 00:00:00
abstract::Adenine nucleotides play an important role in the control of membrane potential by acting on ATP-sensitive K+ (K(ATP)) channels and, in turn, modulating the open probability of voltage-gated Ca2+ channels in pancreatic islet beta-cells. Here, we provide evidence that guanine nucleotides (GNs) also may be involved in t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00356-1
更新日期:2000-03-01 00:00:00
abstract::The present study investigated the presence of ryanodine receptors in the trematode Schistosoma mansoni. [3H]Ryanodine specific binding sites were found in the four subcellular fractions of S. mansoni; however, more binding sites were recovered in the heterogeneous fraction P1 and the microsomal fraction P4, as was th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00219-6
更新日期:1998-10-15 00:00:00
abstract::Gemcitabine (dFdC) is a new cytidine analogue which is active mainly by the incorporation of its triphosphate (dFdCTP) into DNA, leading to cell death. We determined incorporation of dFdC into nucleic acids of two solid tumour cell lines: the murine colon carcinoma cell line Colon 26-10, the human ovarian carcinoma ce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90566-f
更新日期:1993-08-17 00:00:00
abstract::Treatment of immature 21-day-old female Sprague-Dawley rats with 17 beta-estradiol (E2) (0.5 microgram/rat) caused a significant increase in uterine wet weight, DNA synthesis, progesterone receptor (PR) binding, and peroxidase activity. At doses as high as 40 mg/rat, the bioflavonoid naringenin did not cause a signifi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02061-6
更新日期:1995-10-26 00:00:00
abstract::Selective antagonists for the adenosine A(3) receptor (A3AR), a member of the G protein-coupled receptors, have been indicated as potential drugs for anti-asthma or anti-inflammation. However, potent antagonists for the rodent A3AR have not been identified. To evaluate the pharmacological effects of human A3AR antagon...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.08.003
更新日期:2005-11-15 00:00:00
abstract::The reaction mechanism of DNA topoisomerase II (TOP2) involves a covalent double-strand break intermediate in which the enzyme is coupled to DNA via a 5'-phosphotyrosyl bond. This normally transient enzyme-bridged break is stabilised by drugs such as mitoxantrone, mAMSA, etoposide, doxorubicin, epirubicin and idarubic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.12.015
更新日期:2016-03-01 00:00:00