Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism.
Background and Purpose: Chronic obstructive pulmonary disease (COPD) is a corticosteroid-resistant airway inflammatory condition. Resveratrol exhibits anti-inflammatory activities in COPD but has weak potency and poor pharmacokinetics. This study aimed to evaluate the potential of isorhapontigenin,...
| Publicado en: | British Journal of Pharmacology Vol. 174; no. 13; pp. 2043 - 2060 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jul2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=123521996&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 123521996 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00071188 DZ6 jtl: British Journal of Pharmacology issn: 00071188 maglogo: Y pubinfo: dt: Jul2017 vid: 174 iid: 13 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 123521996 123521996 NLM28369685 123521996 10.1111/bph.13803 NLM28369685 123521996 ppf: 2043 ppct: 17 formats: tig: atl: Isorhapontigenin, a bioavailable dietary polyphenol, suppresses airway epithelial cell inflammation through a corticosteroid-independent mechanism. aug: au: Yeo, Samuel Chao Ming Fenwick, Peter S Barnes, Peter J Lin, Hai Shu Donnelly, Louise E affil: Airway Disease, National Heart and Lung Institute, Imperial College London, London UK sug: subj: Antiinflammatory Agents Pharmacodynamics Respiratory System Drug Effects Adrenal Cortex Hormones Pharmacodynamics Inflammation Drug Therapy Stilbenes Pharmacodynamics Epithelial Cells Drug Effects Molecular Structure Pulmonary Disease, Chronic Obstructive Pathology Antiinflammatory Agents Dose-Response Relationship, Drug Male Biochemical Phenomena Epithelial Cells Metabolism Biological Availability Tumor Cells, Cultured Rats Antiinflammatory Agents Administration and Dosage Stilbenes Administration and Dosage Pulmonary Disease, Chronic Obstructive Metabolism Pulmonary Disease, Chronic Obstructive Drug Therapy Stilbenes Administration, Oral Female Cell Physiology Drug Effects Injections, Intravenous Respiratory System Metabolism Inflammation Metabolism Aged Animal Studies Human In Vivo Studies Aged: 65+ years Male Female ab: Background and Purpose: Chronic obstructive pulmonary disease (COPD) is a corticosteroid-resistant airway inflammatory condition. Resveratrol exhibits anti-inflammatory activities in COPD but has weak potency and poor pharmacokinetics. This study aimed to evaluate the potential of isorhapontigenin, another dietary polyphenol, as a novel anti-inflammatory agent for COPD by examining its effects in vitro and pharmacokinetics in vivo.Experimental Approach: Primary human airway epithelial cells derived from healthy and COPD subjects, and A549 epithelial cells were incubated with isorhapontigenin or resveratrol and stimulated with IL-1β in the presence or absence of cigarette smoke extract. Effects of isorhapontigenin and resveratrol on the release of IL-6 and chemokine (C-X-C motif) ligand 8 (CXCL8), and the activation of NF-κB, activator protein-1 (AP-1), MAPKs and PI3K/Akt/FoxO3A pathways were determined and compared with those of dexamethasone. The pharmacokinetic profiles of isorhapontigenin, after i.v. or oral administration, were assessed in Sprague-Dawley rats.Key Results: Isorhapontigenin concentration-dependently inhibited IL-6 and CXCL8 release, with IC50 values at least twofold lower than those of resveratrol. These were associated with reduced activation of NF-κB and AP-1 and, notably, the PI3K/Akt/FoxO3A pathway, that was relatively insensitive to dexamethasone. In vivo, isorhapontigenin was rapidly absorbed with abundant plasma levels after oral dosing. Its oral bioavailability was approximately 50% higher than resveratrol.Conclusions and Implications: Isorhapontigenin, an orally bioavailable dietary polyphenol, displayed superior anti-inflammatory effects compared with resveratrol. Furthermore, it suppressed the PI3K/Akt pathway that is insensitive to corticosteroids. These favourable efficacy and pharmacokinetic properties support its further development as a novel anti-inflammatory agent for COPD. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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