{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:43:14Z","timestamp":1788176594535,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minister Science and Technology, Taiwan","award":["MOST 110-2314-B-214-001"],"award-info":[{"award-number":["MOST 110-2314-B-214-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Airborne fine particulate matter (PM2.5) is a severe problem and is associated with health issues including liver diseases. Workers performing manual labor tend to be alcohol consumers during work, where they are also exposed to PM2.5. Long-term PM2.5 exposure can increase oxidative stress, leading to inflammation. Whether long-term exposure to air pollution and alcohol synergistically increases liver fibrosis risk warrants investigation. Oleanolic acid (OA)\u2014a triterpenoid\u2014has antioxidant and anti-inflammatory activities, but its low water solubility and cytotoxicity impair its potential applications. In this study, we fabricated liposomal OA nanoparticles (Lipo-OAs); then, we evaluated the anti-inflammatory effect on exposed cells and the ameliorative effect of Lipo-OAs on PM2.5 and alcohol-induced liver fibrosis in mice. The half maximal inhibitory concentration of PM2.5 for hepatic stellate cells was 900 \u03bcg\/mL; at a concentration of \u2265600 \u03bcg\/mL, PM2.5 significantly increased interleukin-6 and tumor necrosis factor-\u03b1 production. OA encapsulation in Lipo-OAs, 353 \u00b1 140 nm in diameter with 79% encapsulation efficiency, significantly reduced OA cytotoxicity. Lipo-OAs treatment significantly reduced alanine aminotransferase, aspartate aminotransferase, and \u03b3-glutamyltransferase levels; histologically, it alleviated steatosis and improved Ishak\u2019s modified HAI score. In conclusion, Lipo-OAs have potential anti-inflammatory and reparative effects for PM2.5 and alcohol-induced liver injury treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics14051108","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T03:16:55Z","timestamp":1653362215000},"page":"1108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Reparative Efficacy of Liposome-Encapsulated Oleanolic Acid against Liver Inflammation Induced by Fine Ambient Particulate Matter and Alcohol in Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Ching-Ting","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering, I-Shou University, Kaohsiung 82445, Taiwan"},{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan"},{"name":"Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chiuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan"},{"name":"Ministry of National Defense-Medical Affairs Bureau, Taipei City 10462, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-2215","authenticated-orcid":false,"given":"Li-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"The School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-3408","authenticated-orcid":false,"given":"Chia-Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyh-Ming","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/jat.1310","article-title":"Beneficial drugs for liver diseases","volume":"28","author":"Muriel","year":"2008","journal-title":"J. Appl. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ayeleso, T.B., Matumba, M.G., and Mukwevho, E. (2017). Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases. Molecules, 22.","DOI":"10.3390\/molecules22111915"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","unstructured":"Shiu, L.-Y., Huang, H.H., Chen, C.Y., Cheng, H.-Y., Chen, C.I., and Kuo, S.M. (2020). Reparative and toxicity-reducing effects of liposome-encapsulated saikosaponin in mice with liver fibrosis. Biosci. Rep., 40.","DOI":"10.1042\/BSR20201219"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis","volume":"22","author":"Ishak","year":"1995","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.jhep.2015.07.020","article-title":"Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models","volume":"63","author":"Zheng","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mokdad, A.A., Lopez, A.D., Shahraz, S., Lozano, R., Stanaway, J., Murray, C.J.L., and Naghavi, M. (2014). Liver cirrhosis mortality in 187 countries between 1980 and 2010: A systematic analysis. BMC Med., 12.","DOI":"10.1186\/s12916-014-0145-y"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45846","DOI":"10.1038\/srep45846","article-title":"International incidence and mortality trends of liver cancer: A global profile","volume":"7","author":"Wong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1039\/C7TX00262A","article-title":"Effects of sub-chronic exposure to atmospheric PM2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats","volume":"7","author":"Li","year":"2018","journal-title":"Toxicol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Im, P.K., Millwood, I.Y., Kartsonaki, C., Guo, Y., Chen, Y., Turnbull, I., Yu, C., Du, H., Pei, P., and Lv, J. (2021). Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: A 10-year prospective study of 0.5 million adults. BMC Med., 19.","DOI":"10.1186\/s12916-021-02079-1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/hep4.1479","article-title":"Pathogenesis of Nonalcoholic Steatohepatitis: An Overview","volume":"4","author":"Parthasarathy","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1136\/jcp.37.7.721","article-title":"Alcohol induced liver disease","volume":"37","author":"Fleming","year":"1984","journal-title":"J. Clin. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jep.2005.05.024","article-title":"Oleanolic acid and ursolic acid: Research perspectives","volume":"100","author":"Liu","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bi, S., Chu, F., Wang, M., Li, B., Mao, P., Zhang, H., Wang, P., Guo, W., Xu, L., and Ren, L. (2016). Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the Proliferation and Induced Apoptosis of Activated HSC-T6 Cells. Molecules, 21.","DOI":"10.3390\/molecules21111599"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Feng, A., Yang, S., Sun, Y., Zhang, L., Bo, F., and Li, L. (2020). Development and Evaluation of Oleanolic Acid Dosage Forms and Its Derivatives. Biomed. Res. Int., 2020.","DOI":"10.1155\/2020\/1308749"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wu, Y.C., Huang, H.H., Wu, Y.J., Manousakas, I., Yang, C.C., and Kuo, S.M. (2019). Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164057"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cadinoiu, A.N., Rata, D.M., Atanase, L.I., Daraba, O.M., Gherghel, D., Vochita, G., and Popa, M. (2019). Aptamer-Functionalized Liposomes as a Potential Treatment for Basal Cell Carcinoma. Polymers, 11.","DOI":"10.3390\/polym11091515"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cadinoiu, A., Rata, D., Atanase, L., Mihai, C., Bacaita, S., and Popa, M. (2021). Formulations Based on Drug Loaded Aptamer-Conjugated Liposomes as a Viable Strategy for the Topical Treatment of Basal Cell Carcinoma-In Vitro Tests. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060866"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.2147\/IJN.S31725","article-title":"Oleanolic acid liposomes with polyethylene glycol modification: Promising antitumor drug delivery","volume":"7","author":"Gao","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"235102","DOI":"10.1088\/0957-4484\/24\/23\/235102","article-title":"An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes","volume":"24","author":"Tang","year":"2013","journal-title":"Nanotechnology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47136","DOI":"10.18632\/oncotarget.17559","article-title":"Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ tox-icity in hepatocellular carcinoma","volume":"8","author":"Sarfraz","year":"2017","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/978-1-4939-2074-7_22","article-title":"Measurement of Albumin Secretion as Functionality Test in Primary Hepatocyte Cultures","volume":"1250","author":"Buyl","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Takahashi, H. (2011). Ishak versus METAVIR: Terminology, Convertibility and Correlation with Laboratory Changes in Chronic Hepatitis C. Liver Biopsy, IntechOpen.","DOI":"10.5772\/811"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1177\/1535370217703978","article-title":"Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems","volume":"242","author":"George","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1007\/s11739-012-0802-0","article-title":"Hypoalbuminemia","volume":"7","author":"Gatta","year":"2012","journal-title":"Intern. Emerg. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2821673","DOI":"10.1155\/2021\/2821673","article-title":"The Roles of Liver Inflammation and the Insulin Signaling Pathway in PM2.5 Instillation-Induced Insulin Resistance in Wistar Rats","volume":"2021","author":"Zhang","year":"2021","journal-title":"Dis. Markers"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.jhep.2009.09.008","article-title":"A novel model of CCl4-induced cirrhosis with ascites in the mouse","volume":"51","author":"Domenicali","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/03602532.2017.1293683","article-title":"Non-alcoholic fatty liver disease (NAFLD)\u2014Pathogenesis, classification, and effect on drug metabolizing enzymes and transporters","volume":"49","author":"Cobbina","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_29","first-page":"170","article-title":"Non-alcoholic Fatty liver disease in children","volume":"40","author":"Singer","year":"2014","journal-title":"Curr. Health Sci. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0168-8278(00)80233-0","article-title":"Mallory bodies revisited","volume":"32","author":"Denk","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.7150\/ijms.46421","article-title":"PM2.5-related cell death patterns","volume":"18","author":"Wang","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3486841","DOI":"10.1155\/2019\/3486841","article-title":"PM2.5 Exposure in the Respiratory System Induces Distinct Inflammatory Signaling in the Lung and the Liver of Mice","volume":"2019","author":"Jeong","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ding, S., Yuan, C., Si, B., Wang, M., Da, S., Bai, L., and Wu, W. (2019). Combined effects of ambient particulate matter exposure and a high-fat diet on oxidative stress and steatohepatitis in mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214680"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yan, W., Zhang, C., Li, B., Xu, X., Liang, M., Gu, S., Chu, F., Xu, B., Ren, J., and Wang, P. (2016). A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation. Molecules, 21.","DOI":"10.3390\/molecules21040402"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jhep.2016.09.017","article-title":"Extensive testing or focused testing of patients with elevated liver enzymes","volume":"66","author":"Tapper","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. (2020). Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells, 9.","DOI":"10.3390\/cells9040875"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Federico, A., Dallio, M., and Loguercio, C. (2017). Silymarin\/Silybin and Chronic Liver Disease: A Marriage of Many Years. Molecules, 22.","DOI":"10.3390\/molecules22020191"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1530-0277.2006.00063.x","article-title":"Silymarin protects against acute ethanol-induced hepatotoxicity in mice","volume":"30","author":"Song","year":"2006","journal-title":"Alcohol. Clin. Exp. Res."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/1108\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:16:43Z","timestamp":1760138203000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/1108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["pharmaceutics14051108"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14051108","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]}}}