{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:50:05Z","timestamp":1786459805157,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Innovation Foundation funded by Ministry of Science and ICT","award":["2023-DD-UP-0007"],"award-info":[{"award-number":["2023-DD-UP-0007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Airborne particulate matter (PM) triggers oxidative stress and inflammation in pulmonary tissues, contributing to chronic respiratory diseases. This study evaluated the antioxidant and anti-inflammatory effects of a combined extract of Haematococcus pluvialis (H. pluvialis) and walnut shell (HW extract) and its protective efficacy against PM2.5-induced pulmonary inflammation. Extracts mixed at different ratios (10:0\u20130:10, w\/w) were tested using 2,2\u2032-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, cell-based assays, HPLC quantification, molecular docking, and a PM2.5-induced pulmonary inflammation mouse model. The optimized 6:4 mixture showed the strongest antioxidant activity (RC50 = 0.61 \u00b1 0.14 \u03bcg\/mL) and significantly reduced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression without cytotoxicity. HPLC confirmed the presence of astaxanthin (1.714 \u03bcg\/mg) and quercetin (0.722 \u03bcg\/mg). Docking simulations indicated strong COX-2 binding affinities (\u22129.501 and \u22128.753 kcal\/mol) through hydrogen bonding and hydrophobic interactions. In vivo, HW extract reduced leukocyte infiltration, serum IL-6 levels, and pulmonary expression of COX-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-\u03b1) while improving alveolar structure. These results suggest that HW extract exerts synergistic antioxidant and anti-inflammatory actions via dual-site COX-2 modulation, providing a promising natural therapeutic approach for mitigating PM2.5-induced respiratory inflammation.<\/jats:p>","DOI":"10.3390\/md23120473","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:32:17Z","timestamp":1765380737000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic Protective Effects of Haematococcus pluvialis-Derived Astaxanthin and Walnut Shell Polyphenols Against Particulate Matter (PM)2.5-Induced Pulmonary Inflammation"],"prefix":"10.3390","volume":"23","author":[{"given":"Hyun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science, College of Health Science, Dankook University, Cheonan-si 31116, Republic of Korea"},{"name":"Marine Bio-Food and Drug Convergence Technology Center, Dankook University, Cheonan-si 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, College of Health Science, Dankook University, Cheonan-si 31116, Republic of Korea"},{"name":"Marine Bio-Food and Drug Convergence Technology Center, Dankook University, Cheonan-si 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Gyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, College of Health Science, Dankook University, Cheonan-si 31116, Republic of Korea"},{"name":"Marine Bio-Food and Drug Convergence Technology Center, Dankook University, Cheonan-si 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/toxres\/tfac001","article-title":"PM2.5 induces inflammatory responses via oxidative stress-mediated mitophagy in Bronchial Epithelial Cells","volume":"11","author":"Zhai","year":"2022","journal-title":"Toxicol. 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