{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:27:11Z","timestamp":1791260831253,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T00:00:00Z","timestamp":1566259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["105-2622-E-214-002-CC3, 107-2221-E-899-001-MY2"],"award-info":[{"award-number":["105-2622-E-214-002-CC3, 107-2221-E-899-001-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Astaxanthin (Asta) has been demonstrated to possess anti-inflammatory, antitumor, and free radical-clearing activities. However, the poor stability and low water solubility of Asta hamper its bioavailability. The objectives of this study were to fabricate Asta-loaded liposomes (Asta-lipo) and investigate the therapeutic effects of Asta-lipo on alcoholic liver fibrosis in mice. The mice were administered with Asta-lipo or liposomes alone prior to a 3-week dose containing 30% alcohol with or without feeding with a second dose of 30% alcohol. The prepared Asta-lipo of 225.0 \u00b1 58.3 nm in diameter, had an encapsulation efficiency of 98%. A slow release profile of 16.2% Asta from Asta-lipo was observed after a 24-h incubation. Restorative actions against alcoholic liver fibrosis were observed after oral administration of Asta-lipo for 4 weeks. Hepatic repair, followed by a second dose of 30% alcohol, suggested that Asta-lipo exerted protective and reparative effects against liver injuries induced by repeated consumption of alcohol. The changes of serum ALT and AST values were principally in consistence with the histopathologic findings. Asta-lipo exerted rapid and direct effects against repeated alcohol-induced liver disease, whereas Asta-lipo given orally could boost recovery from liver injuries obtained due to previous long-term alcohol use. These data demonstrate that Asta-lipo has applicable protective and therapeutic potential to treat alcohol-induced liver diseases.<\/jats:p>","DOI":"10.3390\/ijms20164057","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T11:19:06Z","timestamp":1566386346000},"page":"4057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis"],"prefix":"10.3390","volume":"20","author":[{"given":"Yu Chiuan","family":"Wu","sequence":"first","affiliation":[{"name":"Hualien Armed Forces General Hospital, Hualien County 97144, Taiwan"},{"name":"National Kaohsiung University of Hospitality and Tourism, Kaohsiung City 81271, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chiayi University, Chiayi City 60054, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Jhen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung City 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Manousakas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung City 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Chang","family":"Yang","sequence":"additional","affiliation":[{"name":"Bioptik Technology, INC, Miaoli County 36045, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyh Ming","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung City 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jhep.2013.03.007","article-title":"Global burden of alcoholic liver diseases","volume":"59","author":"Rehm","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.5348\/ijhpd-2017-73-ED-9","article-title":"In vitro studies of alcohol-induced liver injury in virally-infected human hepatocytes: Advantages and limitations","volume":"7","author":"Natalia","year":"2017","journal-title":"Int. J. Hepatobiliary Pancreat. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fphys.2012.00193","article-title":"Acute alcohol-induced liver injury","volume":"3","author":"Massey","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_4","first-page":"183","article-title":"Intake of specific carotenoids and lung cancer risk","volume":"2","author":"Hankin","year":"1993","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3390\/md12010128","article-title":"Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications\u2014A Review","volume":"12","author":"Ambati","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jnutbio.2016.01.006","article-title":"Astaxanthin inhibits inflammation and fibrosis in the liver and adipose tissue of mouse models of diet-induced obesity and nonalcoholic steatohepatitis","volume":"43","author":"Kim","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1021\/jf991106k","article-title":"Antioxidant Activities of Astaxanthin and Related Carotenoids","volume":"48","author":"Naguib","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17192","DOI":"10.1038\/srep17192","article-title":"Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E","volume":"5","author":"Ni","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1556-276X-8-102","article-title":"Liposome: Classification, preparation, and applications","volume":"8","author":"Akbarzadeh","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bulbake, U., Doppalapudi, S., Kommineni, N., and Khan, W. (2017). Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9020012"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fphar.2015.00286","article-title":"Advances and Challenges of Liposome Assisted Drug Delivery","volume":"6","author":"Sercombe","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.3233\/BME-140997","article-title":"Characterization and human osteoblastic proliferation- and differentiation-stimulatory effects of phosphatidylcholine liposomes-encapsulated propranolol hydrochloride","volume":"24","author":"Teong","year":"2014","journal-title":"Bio-Med. Mater. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.afos.2017.08.026","article-title":"Liposomal encapsulation for systemic delivery of propranolol via transdermal iontophoresis improves bone microarchitecture in ovariectomized rats","volume":"3","author":"Chen","year":"2017","journal-title":"Osteoporos. Sarcopenia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/hep.22109","article-title":"Public Policy Committee of the American Association for the Study of Liver, D. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease","volume":"47","author":"Kim","year":"2008","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/j.bbamem.2015.04.010","article-title":"Interference of phosphatidylcholines with in-vitro cell proliferation\u2014No flock without black sheep","volume":"1848","author":"Werlein","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3109\/15376516.2012.666651","article-title":"Effects of long term ethanol consumption mediated oxidative stress on neovessel generation in liver","volume":"22","author":"Das","year":"2012","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/712893","article-title":"Toxic Damage Increases Angiogenesis and Metastasis in Fibrotic Livers via PECAM-1","volume":"2014","author":"Raskopf","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1024\/0300-9831.75.5.333","article-title":"Oxidative Stress and Antioxidant Status in Rat Blood, Liver and Muscle: Effect of Dietary Lipid, Carnitine and Exercise","volume":"75","author":"Karanth","year":"2005","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1743-7075-8-65","article-title":"The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats","volume":"8","author":"Dhibi","year":"2011","journal-title":"Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3727\/105221617X695519","article-title":"Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance","volume":"17","author":"Gao","year":"2017","journal-title":"Gene Expr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/hep.23837","article-title":"Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3","volume":"52","author":"Ki","year":"2010","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1111\/j.1572-0241.1999.01006.x","article-title":"The ratio of aspartate aminotransferase to alanine aminotransferase: Potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease","volume":"94","author":"Sorbi","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0016-5085(84)80110-9","article-title":"Relationship between pyridoxal 5\u2019-phosphate deficiency and aminotransferase levels in alcoholic hepatitis","volume":"86","author":"Diehl","year":"1984","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"357287","DOI":"10.1155\/2014\/357287","article-title":"Noninvasive Biomarkers of Liver Fibrosis: An Overview","volume":"2014","author":"Fallatah","year":"2014","journal-title":"Adv. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11044","DOI":"10.3748\/wjg.v21.i39.11044","article-title":"Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease","volume":"21","author":"Lombardi","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.phymed.2015.05.054","article-title":"Astaxanthin induces angiogenesis through Wnt\/beta-catenin signaling pathway","volume":"22","author":"Xu","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.3390\/md13052857","article-title":"Astaxanthin from Haematococcus pluvialis Prevents Oxidative Stress on Human Endothelial Cells without Toxicity","volume":"13","author":"Bastias","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3164\/jcbn.14-109","article-title":"Anti-inflammatory effects of astaxanthin in the human gingival keratinocyte line NDUSD-1","volume":"56","author":"Miyachi","year":"2015","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.3390\/md13063368","article-title":"Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS\/MAPK Pathway in Mice","volume":"13","author":"Li","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"954502","DOI":"10.1155\/2014\/954502","article-title":"Protective effect of astaxanthin on liver fibrosis through modulation of TGF-beta1 expression and autophagy","volume":"2014","author":"Shen","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, G., Ni, Y., Nagata, N., Xu, L., and Ota, T. (2016). Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091379"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbagen.2014.10.014","article-title":"Astaxanthin prevents TGFbeta1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells","volume":"1850","author":"Yang","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.4103\/pr.pr_26_17","article-title":"Astaxanthin Ameliorates Hepatic Damage and Oxidative Stress in Carbon Tetrachloride-administered Rats","volume":"9","author":"Islam","year":"2017","journal-title":"Pharmacogn. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/15376516.2015.1124956","article-title":"Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver","volume":"26","author":"Reza","year":"2016","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, Y.J., Wu, Y.C., Chen, I.-F., Wu, Y.-L., Chuang, C.W., Huang, H.H., and Kuo, S.M. (2018). Reparative Effects of Astaxanthin-Hyaluronan Nanoaggregates against Retrorsine-CCl4-Induced Liver Fibrosis and Necrosis. Molecules, 23.","DOI":"10.3390\/molecules23040726"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0044-8486(86)90358-3","article-title":"Instrumental colour analysis of farmed and wild Atlantic salmon when raw, baked and smoked","volume":"53","author":"Skrede","year":"1986","journal-title":"Aquaculture"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.burns.2019.01.010","article-title":"Liposome-encapsulated farnesol accelerated tissue repair in third-degree burns on a rat model","volume":"45","author":"Wu","year":"2019","journal-title":"Burns"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.actbio.2017.09.028","article-title":"In vitro and in vivo study of the application of volvox spheres to co-culture vehicles in liver tissue engineering","volume":"63","author":"Chang","year":"2017","journal-title":"Acta Biomater."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/4057\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:12:21Z","timestamp":1760188341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/4057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,20]]},"references-count":38,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20164057"],"URL":"https:\/\/doi.org\/10.3390\/ijms20164057","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,20]]}}}