{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:13:02Z","timestamp":1790802782050,"version":"4.1.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Xinfeng Capsule (XFC) is a traditional Chinese medicine compound preparation that has been clinically used to treat rheumatoid arthritis (RA) for more than 20 years. It has demonstrated clear therapeutic effects, including improving pulmonary function and reducing lung injury in patients with RA. However, the precise mechanism underlying its protective effect against lung injury remains unclear. This study aims to explore the potential mechanisms of XFC in the treatment of lung injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Liquid chromatography-mass spectrometry (LC-MS) analysis was conducted to determine the chemical composition of XFC. Proteomic and bioinformatic analyses of differentially expressed proteins (DEPs) in rat lung tissue were performed using tandem mass tag labeling. A rat adjuvant arthritis (AA) model was established using Freund\u2019s complete adjuvant to observe pathological changes in synovial and lung tissues, as well as alterations in lung function. In addition, a cell model was constructed by inducing lung fibroblasts with transforming growth factor-\u03b21 (TGF-\u03b21) to investigate the effects of XFC-containing serum on oxidative stress and pulmonary fibrosis through the peroxisome proliferator-activated receptor gamma (PPAR\u03b3)\/3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LC-MS analysis identified a total of 867 compounds in XFC, of which 25 unique compounds were closely associated with pulmonary fibrosis and lung injury. Proteomic analysis suggested that XFC may regulate PPAR signaling pathway-related proteins and alleviate lung injury in AA rats. Animal experiments showed that XFC significantly inhibited immune inflammation, synovial hyperplasia, and oxidative stress in AA rats, while reducing lung injury and improving lung function. Furthermore, XFC-containing serum suppressed TGF-\u03b21\u2013induced proliferation of lung fibroblasts, promoted PPAR\u03b3 expression, and significantly decreased the levels of interleukin-6, tumor necrosis factor-\u03b1, reactive oxygen species, nicotinamide adenine dinucleotide phosphate oxidase 4, HMGCS2, collagen type I \u03b1 1, collagen type III \u03b1 1, and \u03b1-smooth muscle actin (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.01). In addition, XFC partially reversed the effects of the PPAR\u03b3 antagonist GW9662, activated the PPAR\u03b3 signaling pathway, inhibited oxidative stress and inflammatory responses, and exerted anti-fibrotic effects similar to those of the PPAR\u03b3 agonist rosiglitazone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>XFC inhibits inflammation and oxidative stress by regulating the PPAR\u03b3\/HMGCS2 pathway, thereby attenuating fibrosis and alleviating lung injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1599745","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:51:06Z","timestamp":1759913466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Xinfeng Capsule inhibits oxidative stress via regulating the PPAR\u03b3\/ Hmgcs2 signaling pathway in lung tissue of adjuvant arthritis rats"],"prefix":"10.3389","volume":"16","author":[{"given":"Ping-Heng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology, The Affiliated TCM Hospital of Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Rheumatology and Immunology Department, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103056","DOI":"10.1016\/j.autrev.2022.103056","article-title":"Pathogenesis, clinical features, and treatment strategy for rheumatoid arthritis-associated interstitial lung disease","volume":"21","author":"Akiyama","year":"2022","journal-title":"Autoimmun. 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