Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives.

Abstract:

:Chrysin, a natural flavone compound found in plants, has anti-inflammatory activity that has been previously explained in part by the suppression of promoter activities of pro-inflammatory enzymes, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Here we present evidence that several chrysin derivatives modulate the activities, as well as the expression, of COX-2 and iNOS enzymes. Nitrate production triggered by lipopolysaccharide (LPS) was suppressed by treatment of cultured Raw264.7 cells (mice macrophage/monocyte) with chrysin, 5-hydroxy-7-methoxyflavone (Ch-2), and 5,7-diacetylflavone (Ch-4). Interestingly, COX-2 enzyme was strongly inhibited by Ch-4 (IC(50)=2.7 microM) but not by other derivatives. Furthermore, the inhibition of COX enzyme by Ch-4 was selective for COX-2 over COX-1. Three-dimensional modeling showed that Ch-4 fits well into the binding pocket of COX-2. The modeling suggested that a hydrogen bond exists between the oxygen of the ketone group at the 7-position of Ch-4 and the hydroxyl group of Tyr355. Docking Ch-4 into the V523I mutant of COX-2 indicated that Ile523 of COX-1 might contribute to the selectivity of COX-2 over COX-1. Ch-4 showed no effect on iNOS activity. Chrysin and Ch-2 weakly inhibited iNOS enzyme activity in the hemoglobin assay, but the underlying mechanisms of inhibition of iNOS by chrysin are not understood.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Cho H,Yun CW,Park WK,Kong JY,Kim KS,Park Y,Lee S,Kim BK

doi

10.1016/s1043-6618(03)00248-2

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

37-43

issue

1

eissn

1043-6618

issn

1096-1186

pii

S1043661803002482

journal_volume

49

pub_type

杂志文章
  • Antiretroviral drugs in HIV-infected children.

    abstract::Availability of highly active antiretroviral therapy has dramatically increased survival rates and substantially modified the course of HIV infection, which has now become a chronic disease both in adults and in children. Treatment strategies in paediatric patients have to face with specific challenges associated with...

    journal_title:Pharmacological research

    pub_type: 社论,评审

    doi:10.1016/j.phrs.2011.01.007

    authors: Viganò A,Manfredini V,Penagini F,Giacomet V,Zuccotti GV

    更新日期:2011-07-01 00:00:00

  • The inhibition of platelet aggregation by activated macrophages is blocked by dexamethasone.

    abstract::The effect of dexamethasone on the ability of activated J774 macrophages to inhibit platelet aggregation was investigated. After 24h incubation with lipopolysaccharide and gamma-interferon, J774 cells generated large amounts of nitric oxide and inhibited platelet aggregation. Incubation of the cells with dexamethasone...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1993.1016

    authors: Pinto A,Carnuccio R,Sorrentino R,Di Rosa M

    更新日期:1993-02-01 00:00:00

  • alpha-Synuclein: a therapeutic target for Parkinson's disease?

    abstract::Parkinson's disease is a progressive age-related neurodegenerative disease with invariant loss of substantia nigra dopamine neurons and striatal projections. This disorder is well known for the associated motoric symptoms including resting tremor and the inability to initiate movement. However, it is now apparent that...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2008.09.006

    authors: Maguire-Zeiss KA

    更新日期:2008-11-01 00:00:00

  • Pharmacological studies of cardamom oil in animals.

    abstract::Cardamom seeds are widely used for flavouring purposes in food and as carminative. Little information has been reported on their pharmacological and toxicological properties or, for their volatile oil which constitutes about 5% of the seed's total weight. A comparative study of the anti-inflammatory activity of the oi...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0067

    authors: al-Zuhair H,el-Sayeh B,Ameen HA,al-Shoora H

    更新日期:1996-07-01 00:00:00

  • Purinergic P2Y6 receptors: A new therapeutic target of age-dependent hypertension.

    abstract::Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertensi...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2017.03.013

    authors: Sunggip C,Nishimura A,Shimoda K,Numaga-Tomita T,Tsuda M,Nishida M

    更新日期:2017-06-01 00:00:00

  • Influence of 3-PPP, a sigma receptor ligand, on the anticonvulsive action of conventional antiepileptic drugs.

    abstract::(+)-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine (3-PPP; a sigma receptor ligand), administered at 30 mg kg-1, 30 min before the test, significantly decreased the electroconvulsive threshold in mice, being ineffective in lower doses. 3-PPP (20 mg kg-1) diminished the protective activity of diphenylhydantoin, phenobarbi...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1999.0548

    authors: Borowicz KK,Kleinrok Z,Czuczwar SJ

    更新日期:1999-12-01 00:00:00

  • Candidate drugs against SARS-CoV-2 and COVID-19.

    abstract::Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infect...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2020.104859

    authors: McKee DL,Sternberg A,Stange U,Laufer S,Naujokat C

    更新日期:2020-07-01 00:00:00

  • Nutraceuticals: An emerging therapeutic approach against the pathogenesis of Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is regarded as a progressive and devastating neurodegenerative disorder. In aged individuals, it is the most prevalent cause of dementia and is characterized by gradual loss of cognitive functions. In the last decade, numerous research works were undertaken to investigate the pathogenesis of A...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2017.11.028

    authors: Sadhukhan P,Saha S,Dutta S,Mahalanobish S,Sil PC

    更新日期:2018-03-01 00:00:00

  • Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications.

    abstract::Mammals and their intestinal microbiota peacefully coexist in a mutualistic relationship. Commensal bacteria play an active role in shaping and modulating physiological processes in the host, which include, but are not restricted to, the immune system and the intestinal barrier. Both play a crucial role in containing ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2012.10.007

    authors: Natividad JM,Verdu EF

    更新日期:2013-03-01 00:00:00

  • iRAGE as a novel carboxymethylated peptide that prevents advanced glycation end product-induced apoptosis and endoplasmic reticulum stress in vascular smooth muscle cells.

    abstract::Advanced glycation end-products (AGE) and the receptor for AGE (RAGE) have been linked to numerous diabetic vascular complications. RAGE activation promotes a self-sustaining state of chronic inflammation and has been shown to induce apoptosis in various cell types. Although previous studies in vascular smooth muscle ...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2015.12.015

    authors: Maltais JS,Simard E,Froehlich U,Denault JB,Gendron L,Grandbois M

    更新日期:2016-02-01 00:00:00

  • Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer.

    abstract::Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the prog...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2016.12.005

    authors: Wang Y,Xu M,Ke ZJ,Luo J

    更新日期:2017-01-01 00:00:00

  • The distribution of catecholamines between plasma and platelets in cyclosporin A-induced hypertensive rats.

    abstract::One of the most serious side effects of the immunosuppressive agent, cyclosporin A (CsA), is drug-related hypertension. As it is generally accepted, the sympathetic nervous system may play an important role in the development or maintenance of this abnormal pathophysiological situation. This study is aimed at assessin...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1999.0572

    authors: Reis F,Tavares P,Teixeira F

    更新日期:2000-02-01 00:00:00

  • Evidence for a role of nitric oxide in the mediation of antiproliferative UVA effects in keratinocytes.

    abstract::Using cultured human keratinocytes, the present study investigates the role of nitric oxide (NO) in the mediation of the antiproliferative effects of ultraviolet light A (UVA). UVA treatment of cells (3-21 J cm (-2)) caused a time- and dose-dependent increase in nitrite formation in a micromolar range. This effect was...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.2001.0939

    authors: Podhaisky HP,Klapperstück T,Riemschneider S,Wohlrab W

    更新日期:2002-03-01 00:00:00

  • Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.

    abstract::Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2009.09.002

    authors: Marrachelli VG,Miranda FJ,Centeno JM,Burguete MC,Castelló-Ruiz M,Jover-Mengual T,Pérez AM,Salom JB,Torregrosa G,Alborch E

    更新日期:2010-02-01 00:00:00

  • A case-control study of the effects of hydroxyurea on circulating cortisol levels in patients with acute myelogenous leukemia and chronic myeloproliferative disorders.

    abstract::We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological condi...

    journal_title:Pharmacological research

    pub_type: 临床试验,杂志文章

    doi:10.1006/phrs.2000.0709

    authors: Navarra P,Aloe-Spiriti MA,Boccarini F,Montefusco E,Latagliata R,Preziosi P,Petti MC

    更新日期:2000-10-01 00:00:00

  • Studies on the glycemic and lipidemic effect of monopril and losartan in normal and diabetic rats.

    abstract::The effects of the angiotensin-converting enzyme (ACE) inhibitor monopril and the angiotensin II receptor blocker losartan on serum glucose, protein levels and some serum lipid components were compared in normal and diabetic rats receiving oral antidiabetic drugs 'repaglinide or gliclazide'. The two antihypertensive a...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2003.12.019

    authors: el-Batran SA,el-Shenawy SM,Nofal SM,Abdel-Salam OM,Arbid MS

    更新日期:2004-08-01 00:00:00

  • Oxaceprol, an atypical inhibitor of inflammation and joint damage.

    abstract::Oxaceprol, an established therapeutic agent for osteoarthritis, had no effect on macrophage prostaglandin E2 release in vitro and inhibited carrageenan paw oedema at high doses (18-150 mg/kg p.o.). In the same dose range, oxaceprol was comparable to indomethacin (3 mg/kg p.o.) as an inhibitor of yeast hyperalgaesia an...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1996.0051

    authors: Ionac M,Parnham MJ,Plauchithiu M,Brune K

    更新日期:1996-06-01 00:00:00

  • Sirt3 is a novel target to treat sepsis induced myocardial dysfunction by acetylated modulation of critical enzymes within cardiac tricarboxylic acid cycle.

    abstract::Sepsis induced myocardial dysfunction (SIMD) results in high morbidity and mortality. However, the effective therapeutic strategies for SIMD treatment remain limited. Sirt3 is the main mitochondrial Sirtuin member and is a key modulator of mitochondrial metabolism and function. In this study, we aimed to investigate t...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2020.104887

    authors: Xu Y,Zhang S,Rong J,Lin Y,Du L,Wang Y,Zhang Z

    更新日期:2020-09-01 00:00:00

  • Effect of captopril on doxorubicin-induced nephrotoxicity in normal rats.

    abstract::Biochemical evaluations of the effects of the sulfhydryl-containing angiotensin-converting enzyme inhibitor (captopril) on the nephrotoxicity induced by doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg kg-1) which caused nephrotoxicity was manifested biochemically by the elevation of se...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.1998.0432

    authors: Mansour MA,El-Kashef HA,Al-Shabanah OA

    更新日期:1999-03-01 00:00:00

  • Antisense oligonucleotides as therapeutic agents.

    abstract::The potential for modulating gene expression by the use of antisense oligonucleotides has become increasingly interesting in recent years. Antisense oligonucleotides are complementary nucleic acid fragments that hybridize to target sequences within RNA to form a DNA-RNA duplex, resulting in the block of translation of...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1006/phrs.1997.0227

    authors: Alama A,Barbieri F,Cagnoli M,Schettini G

    更新日期:1997-09-01 00:00:00

  • Interaction of progesterone derivatives with the digitalis target enzyme: impact of glycosidation on inhibitory potency.

    abstract::As a function of the structural modification of the steroid nucleus, the inhibitory interaction of 11 progesterone derivatives with human Na/K-ATPase (Na+/K(+)-transporting ATPase, EC 3.6.1.37), through C3-O-rhamnosylation, is either much decreased or weakly up to strongly increased, so that the rhamnosyl residue cont...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/s1043-6618(05)80102-1

    authors: Weiland J,Schönfeld W,Menke KH,Repke KR

    更新日期:1991-01-01 00:00:00

  • Direct inotropic effects of propofol and adenosine on rat atrial muscle: possible mechanisms.

    abstract::Experiments were designed to evaluate the mechanisms of propofol and adenosine in rat atrial muscle. Atria were suspended in the isolated organ bath system for isometric tension recording and response to propofol and adenosine were tested in the absence and presence of glibenclamide, N(G)-nitro-arginine-methyl-ester (...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1006/phrs.2000.0666

    authors: Cinel I,Gür S

    更新日期:2000-08-01 00:00:00

  • QiShenYiQi Pills® ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway.

    abstract::QiShenYiQi Pills (QSYQ) is a compound Chinese medicine widely used in China for treatment of cardiovascular disease. However, limited data are available regarding the anti-fibrotic role of QSYQ after ischemia/reperfusion (I/R) injury. This study aimed to investigate the effect of post-treatment with QSYQ on myocardial...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/j.phrs.2019.104272

    authors: Zheng QN,Wei XH,Pan CS,Li Q,Liu YY,Fan JY,Han JY

    更新日期:2019-08-01 00:00:00

  • NGF and heart: Is there a role in heart disease?

    abstract::The review emphasizes the role of NGF, the most representative member of the neurotrophins family, in cardiac physiopathology with a particular focus on healing and sprouting processes occurring after tissue damage. Cardiac and circulating NGF levels dramatically increase following myocardial injury (MI). A very early...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2010.12.017

    authors: Govoni S,Pascale A,Amadio M,Calvillo L,D'Elia E,Cereda C,Fantucci P,Ceroni M,Vanoli E

    更新日期:2011-04-01 00:00:00

  • Differential effects of central and peripheral cholinergic blockade on water consumption by rats.

    abstract::Atropine (5 mg/kg, s.c., twice daily) had no significant effect on 24-h water consumption on day 1 of treatment; on subsequent days the rats showed a significant increase. Procyclidine (5 mg/kg, s.c., twice daily) had a similar effect, except that the increase in daily water consumption began on the third day of treat...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/1043-6618(90)90745-y

    authors: Alharbi MM,Maickel RP

    更新日期:1990-01-01 00:00:00

  • The epicardium as a source of multipotent adult cardiac progenitor cells: Their origin, role and fate.

    abstract::Since the regenerative capacity of the adult mammalian heart is limited, cardiac injury leads to the formation of scar tissue and thereby increases the risk of developing compensatory heart failure. Stem cell therapy is a promising therapeutic approach but is facing problems with engraftment and clinical feasibility. ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2017.07.020

    authors: Smits AM,Dronkers E,Goumans MJ

    更新日期:2018-01-01 00:00:00

  • Pharmacological modulation in mesial temporal lobe epilepsy: Current status and future perspectives.

    abstract::Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and geneti...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2016.09.019

    authors: Gambardella A,Labate A,Cifelli P,Ruffolo G,Mumoli L,Aronica E,Palma E

    更新日期:2016-11-01 00:00:00

  • Harnessing ionic mechanisms to achieve disease modification in neurodegenerative disorders.

    abstract::Progressive neuronal death is the key pathogenic event leading to clinical symptoms in neurodegenerative disorders (NDDs). Neuroprotective treatments are virtually unavailable, partly because of the marked internal heterogeneity of the mechanisms underlying pathology. Targeted neuroprotection would require deep mechan...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审

    doi:10.1016/j.phrs.2019.104343

    authors: Masi A,Narducci R,Mannaioni G

    更新日期:2019-09-01 00:00:00

  • Biochemical and hematological side effects of clofazimine in leprosy patients.

    abstract::Gastrointestinal toxicity and red skin discoloration were the major side effects observed in leprosy patients undergoing long-term treatment with clofazimine (CFZ). Hematological and biochemical alterations have been cited among other side effects; however, their real magnitude and clinical significance at the doses c...

    journal_title:Pharmacological research

    pub_type: 临床试验,杂志文章

    doi:10.1016/s1043-6618(02)00086-5

    authors: Costa Queiroz RH,de Souza AM,Sampaio SV,Melchior E Jr

    更新日期:2002-08-01 00:00:00

  • Vigabatrin does not affect the intestinal absorption of phenytoin in rat duodeno-jejunal loops in situ.

    abstract::The antiepileptic drug vigabatrin (GVG) is known to decrease significantly the serum concentration of concurrently administered phenytoin (PHT) in epileptic patients. To assess a possible mechanism for this interaction, the effect of GVG on the intestinal absorption of PHT was investigated by means of circulation expe...

    journal_title:Pharmacological research

    pub_type: 杂志文章

    doi:10.1016/s1043-6618(05)80133-1

    authors: Tonini M,Gatti G,Manzo L,Olibet G,Coccini T,Perucca E

    更新日期:1992-09-01 00:00:00