{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T03:59:47Z","timestamp":1780891187976,"version":"3.54.1"},"reference-count":79,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pulmonary fibrosis (PF) is a progressive condition characterized by inflammation and excessive fibrous tissue formation. Pirfenidone, an FDA\u2010approved drug, slows PF progression through reducing TGF\u2010\u03b2 production and antioxidant effects. Quercetin (Quer) has emerged as a promising candidate for PF management, exhibiting anti\u2010inflammatory and antioxidant effects and inhibiting collagen synthesis in various tissues. Our study was designed to explore the therapeutic potential of combining Pirf and Quer in mitigating bleomycin\u2010induced lung fibrosis in\u00a0vivo. Using a bleomycin (BLM)\u2010induced lung fibrosis model, the study evaluated the anti\u2010fibrotic effects of Pirf and Quer, both individually and together. Oxidative stress biomarkers (MDA, SOD, GSH\u2010Px), inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2), and gene expression of NF\u2010\u03baB, PPAR\u2010\u03b3, PI3K, TLR\u20104, and MAPK were measured to assess the cellular response. BLM exposure markedly upregulated inflammatory markers and oxidative stress, with reducing antioxidant defense mechanisms. Treatment with Pirf moderately decreased these fibrotic changes. Quer, known for its potent antioxidant properties, exhibited a stronger reduction in these parameters. BLM treatment increased the expression of NF\u2010\u03baB, PI3K, TLR\u20104, and MAPK while Pirf and Quer were shown to reduce them significantly. However, PPAR\u2010\u03b3 mRNA levels were reduced by BLM treatment and increased by both Pirf and Quer. Notably, the concomitant administration of Pirf and Quer always provided an augmented effect. The combined administration of Pirf and Quer significantly alleviated BLM\u2010induced lung fibrosis more effectively than either drug alone, suggesting that this combination therapy could enhance anti\u2010fibrotic treatments and should be further investigated in clinical settings.<\/jats:p>","DOI":"10.1002\/prp2.70229","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:03:01Z","timestamp":1772964181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Inflammatory and Oxidative Pathways in Idiopathic Pulmonary Fibrosis: Synergistic Effects of Quercetin and Pirfenidone in Modulating Nrf2\/\n                    <scp>PPAR<\/scp>\n                    \u2010\u03b3 and\n                    <scp>TLR<\/scp>\n                    \u20104\/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathways"],"prefix":"10.1002","volume":"14","author":[{"given":"Hanaa","family":"Wanas","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Taibah University  Madinah Kingdom of Saudi Arabia"},{"name":"Department of Medical Pharmacology, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1219-8459","authenticated-orcid":false,"given":"Amira Karam","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein M.","family":"Elbadawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Taibah University  Madinah Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany 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