{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:11:15Z","timestamp":1792098675747,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T00:00:00Z","timestamp":1646438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Postgraduate Research\uff06Practice Innovation Program of Jiangsu Province","award":["KYCX20_0154"],"award-info":[{"award-number":["KYCX20_0154"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF. Aim: The potential \u201ctherapeutic\u201d effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-\u03b2\/Smad, PI3K\/Akt\/mTOR, and NF-\u03baB signaling pathways. Design\/Methods: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg\/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg\/kg body wt\/day), carotene (10 mg\/kg body wt\/day), or a combination of TRF (200 mg\/kg body wt\/day) and carotene (10 mg\/kg body wt\/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues. Results: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-\u03b21\/Smad, PI3K\/Akt\/mTOR, and NF-\u03baB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg\/kg body wt\/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats. Conclusion: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.<\/jats:p>","DOI":"10.3390\/nu14051094","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:40:02Z","timestamp":1646599202000},"page":"1094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Potential \u201cTherapeutic\u201d Effects of Tocotrienol-Rich Fraction (TRF) and Carotene \u201cAgainst\u201d Bleomycin-Induced Pulmonary Fibrosis in Rats via TGF-\u03b2\/Smad, PI3K\/Akt\/mTOR and NF-\u03baB Signaling Pathways"],"prefix":"10.3390","volume":"14","author":[{"given":"Yifei","family":"Lu","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6224-8277","authenticated-orcid":false,"given":"Yihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-5497","authenticated-orcid":false,"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-3732","authenticated-orcid":false,"given":"Hui","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-7655","authenticated-orcid":false,"given":"Shaokang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Palm Oil Research and Technical Service Institute of Malaysian Palm Oil Board, Shanghai 201108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoong Jun","family":"Hao","sequence":"additional","affiliation":[{"name":"Palm Oil Research and Technical Service Institute of Malaysian Palm Oil Board, Shanghai 201108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-2185","authenticated-orcid":false,"given":"Guiju","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S2213-2600(20)30225-3","article-title":"Pulmonary fibrosis and COVID-19: The potential role for antifibrotic therapy","volume":"8","author":"George","year":"2020","journal-title":"Lancet Respir. 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