{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T15:26:07Z","timestamp":1769354767486,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100030719","name":"National Institute of Health Sciences","doi-asserted-by":"publisher","award":["HL102013 to KR"],"award-info":[{"award-number":["HL102013 to KR"]}],"id":[{"id":"10.13039\/100030719","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Acute respiratory distress syndrome (ARDS)\u2014a form of severe lung injury\u2014is often caused by conditions such as pneumonia, sepsis, and COVID\u201019. COVID\u201019, which enters cells through the angiotensin\u2010converting enzyme 2 (ACE2) receptor, has complications varying from mild infection to ARDS and death. Curcumin, a naturally occurring and safe anti\u2010inflammatory compound, has previously been formulated as a water\u2010soluble curcumin (CDC) to improve solubility and stability under physiologic conditions. CDC administration has been shown to improve cell survival and reduce inflammation, injury, and mortality in models of severe <jats:styled-content style=\"fixed-case\"><jats:italic>Klebsiella pneumoniae<\/jats:italic><\/jats:styled-content> (KP) infection. This study aims to further evaluate the potential of CDC in treating COVID\u201019, particularly complicated by ARDS. Lung samples from post\u2010mortem KP and COVID\u201019 patients were evaluated for relevant markers with immunohistochemistry. Separately, mice inoculated with KP with or without CDC were evaluated for injury, inflammation, and expression of ACE2, STAT\u20103, CXCL\u201010, and IFN\u2010\u03b1. Mice treated with LPS with or without CDC were also evaluated similarly. Lung samples from KP patients had significantly higher ACE2 expression than normal lungs. Postmortem lung samples from COVID\u201019 patients exhibited intense ACE2 staining compared to normal human lungs. Administration of CDC substantially reduced ACE2 expression at serum, gene, and protein levels after KP and LPS infection. Furthermore, CDC administration reduced the levels of STAT\u20103, as well as the chemokine CXCL10, and interferon IFN\u2010\u03b1 in KP\u2010infected mice. In\u00a0vitro, data showed CDC administration reduced ACE2 and STAT3 expression in human lung epithelial cells following KP. Furthermore, administering CDC after LPS led to a significant decrease in injury, inflammation, and ACE2 levels. Based on the promising effects of CDC on these relevant markers, a proposal to use curcumin as a supportive therapy to treat ARDS and COVID\u201019 to save lives is being considered.<\/jats:p>","DOI":"10.1002\/ptr.70046","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T02:03:56Z","timestamp":1752717836000},"page":"3924-3934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oral Administration of Water\u2010Soluble Curcumin Complex Prevents <scp>ARDS<\/scp> With the Potential for <scp>COVID<\/scp>\u201019 Treatment"],"prefix":"10.1002","volume":"39","author":[{"given":"Sinan","family":"Aktay","sequence":"first","affiliation":[{"name":"Department of Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurixi","family":"Lopez\u2010Miranda","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaakko","family":"Parkkinen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishnan","family":"Raghavendran","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3476-9072","authenticated-orcid":false,"given":"Madathilparambil V.","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcme.2016.05.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524019666191016150757"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2072\u20101439.2015.09.31"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.4.1139-1146.1997"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318243d9b1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201007918\u20106"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073673"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.104836"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201081462\u20107"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12111242"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010020\u201002911\u20109"},{"key":"e_1_2_10_13_1","first-page":"742","article-title":"Bacterial Clearance and Cytokine Profiles in a Murine Model of Postsurgical Nosocomial Pneumonia","volume":"11","author":"Manderscheid P. 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