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Three months of LP was evaluated by comparing endogenous cortisol/cortisone conversions to CYP3A4-dependent metabolites and by profiling inflammatory cytokines and chemokines in matched bronchoalveolar lavage fluids. LP did not significantly change CYP3A4 activity but significantly reduced TNF, CCL3, and granzyme B. Post-treatment bronchoalveolar lavage also decreased migration and invasion of human lung neoplastic cells in vitro, supporting LP’s anti-inflammatory and anticancer-relevant potential in the lung microenvironment.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-effects-of-a-grape-seed-procyanidin-extract-on-cytochrome-p450-3a4-activity-and-inflammatory-mediators-in-the-lungs-of-heavy-active-and-former-smokers/331633/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-effects-of-a-grape-seed-procyanidin-extract-on-cytochrome-p450-3a4-activity-and-inflammatory-mediators-in-the-lungs-of-heavy-active-and-former-smokers/331633.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How did the study assess CYP3A4 activity after LP treatment?","Question",{"text":112,"@type":113},"CYP3A4 activity was evaluated by comparing endogenous conversions of cortisol and cortisone to 6-beta-hydroxycortisol and 6-beta-hydroxycortisone before and after LP treatment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What inflammatory mediators changed significantly in bronchoalveolar lavage fluids?",{"text":117,"@type":113},"Three months of LP significantly decreased TNF, CCL3, and granzyme B in matched bronchoalveolar lavage fluids.",{"name":119,"@type":110,"acceptedAnswer":120},"Did LP affect cancer-related cell behavior in vitro?",{"text":121,"@type":113},"Yes. Bronchoalveolar lavage fluids collected after LP treatment significantly reduced migration and invasion of various human lung neoplastic cells in vitro.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331633,1790079583,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Communication  \nThe Effects of a Grape Seed Procyanidin Extract on Cytochrome P450 3A4 Activity and Inflammatory Mediators in the Lungs of Heavy Active and Former Smokers  \nBingye Xue 1, Clifford Qualls 2, Alexander Lanthiez 3, Qing-Yi Lu 4, Jieping Yang 5, Ru-Po Lee 5, Patricia Neis 1 and Jenny T. Mao 1,3, *  \nCitation: Xue, B.; Qualls, C.; Lanthiez, A.; Lu, Q.-Y.; Yang, J.; Lee, R.-P.; Neis, P.; Mao, J.T. The Effects of a Grape Seed Procyanidin Extract on Cytochrome P450 3A4 Activity and Inflammatory Mediators in the Lungs of Heavy Active and Former Smokers. Int. J. Mol. Sci. 2024, 25, 13105 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms252313105  \nAcademic Editor: Simona Serini  \nReceived: 30 October 2024  \nRevised: 26 November 2024  \nAccepted: 27 November 2024  \nPublished: 6 December 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Pulmonary, Critical Care and Sleep Section, New Mexico Veterans Administration Health Care System, University of New Mexico, Albuquerque, NM 87108, USA; [bingye.xue@va.gov](bingye.xue@va.gov) (B.X.); [patricia.neis@va.gov](patricia.neis@va.gov) (P.N.)  \n2 Biostatistics, Biomedical Research Institute of New Mexico, New Mexico Veterans Administration Health Care System, University of New Mexico, Albuquerque, NM 87108, USA; [clifford.qualls@gmail.com](clifford.qualls@gmail.com)  \n3 Pulmonary and Critical Care Section, Veterans Administration San Diego Healthcare System, University of California San Diego, La Jolla, CA 92161, USA; [lanthiez@arizona.edu](lanthiez@arizona.edu)  \n4 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; [qingyilu@ucla.edu](qingyilu@ucla.edu)  \n5 UCLA Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; [jiepingyang@mednet.ucla.edu](jiepingyang@mednet.ucla.edu) (J.Y.); [rupolee@mednet.ucla.edu](rupolee@mednet.ucla.edu) (R.-P.L.)  \n* [Correspondence: jenny.mao@va.gov](Correspondence: jenny.mao@va.gov)  \nAbstract: Grape seed procyanidin extract (GSE) is widely used to promote cardiovascular health and has purported anti-inflammatory properties. Chronic inflammation in the lungs caused by environmental toxins such as tobacco smoking plays a pivotal role in lung cancer development. In a modified phase I lung cancer chemoprevention study conducted in heavy active and former smokers using leucoselect phytosome (LP), a standardized grape seed procyanidin extract complexed with soy phospholipids to enhance bioavailability, three months of LP treatment favorably modulated a variety of surrogate endpoint biomarkers, including markers of cell proliferation. In this correlative study, we further analyzed the effects of LP on cytochrome P450 3A4 (CYP3A4) activities by comparing the endogenous conversions of cortisol and cortisone to 6-beta-hydroxycortisol and 6-beta-hydroxycortisone, respectively, before and after LP treatment and the anti-inflammatory effects of LP in the lung microenvironment of these participants by comparing a profile of inflammatory cytokines and chemokines in matched pre-and post-treatment bronchoalveolar lavage (BAL) fluids. LP treatment did not significantly alter CYP3A4 activity, and three months of LP treatment significantly decreased tumor necrosis factor (TNF), C-C Motif Chemokine Ligand 3 (CCL3) and granzyme B in BAL fluids. Furthermore, post-LP-treatment BAL fluids significantly reduced migration/invasion of various human lung neoplastic cells in vitro. Our findings support the anti-inflammatory effects of GSE/LP in the lung microenvironment and its potential utili","cbCaitdxb4o4LN21","https://ap.wps.com/l/cbCaitdxb4o4LN21","pdf",1677846,14,"English","# Abstract\n# Introduction","[{\"question\":\"How did the study assess CYP3A4 activity after LP treatment?\",\"answer\":\"CYP3A4 activity was evaluated by comparing endogenous conversions of cortisol and cortisone to 6-beta-hydroxycortisol and 6-beta-hydroxycortisone before and after LP treatment.\"},{\"question\":\"What inflammatory mediators changed significantly in bronchoalveolar lavage fluids?\",\"answer\":\"Three months of LP significantly decreased TNF, CCL3, and granzyme B in matched bronchoalveolar lavage fluids.\"},{\"question\":\"Did LP affect cancer-related cell behavior in vitro?\",\"answer\":\"Yes. Bronchoalveolar lavage fluids collected after LP treatment significantly reduced migration and invasion of various human lung neoplastic cells in vitro.\"}]","The Effects of a Grape Seed Procyanidin Extract on Cytochrome P450 3A4 Activity and Inflammatory Mediators in the Lungs of Heavy Active and Former Smokers | PDF",1789994377,35]