{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:23:17Z","timestamp":1790382197284,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council (NSTC), Republic of China","award":["MOST 110-2113-M-018-006"],"award-info":[{"award-number":["MOST 110-2113-M-018-006"]}]},{"name":"National Science and Technology Council (NSTC), Republic of China","award":["MOST 111-2113-M-018-010"],"award-info":[{"award-number":["MOST 111-2113-M-018-010"]}]},{"name":"National Science and Technology Council (NSTC), Republic of China","award":["MOST 111-2320-B-038-058-MY2"],"award-info":[{"award-number":["MOST 111-2320-B-038-058-MY2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted \u03b1-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated \u03b1-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of \u03b1-mangostin on Transforming growth factors-beta 1 (TGF-\u03b21) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). \u03b1-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of \u03b1-mangostin was assessed by carbon tetrachloride (CCl4) treatment mouse model. The data showed that \u03b1-mangostin treatment inhibited TGF-\u03b21-induced Smad2\/3 phosphorylation and alpha-smooth muscle actin (\u03b1-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, \u03b1-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in \u03b1-mangostin-treated HSCs. The CCl4-induced liver fibrosis mouse model showed that the administration of \u03b1-mangostin significantly decreased the expression of the fibrosis markers (\u03b1-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that \u03b1-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, \u03b1-mangostin may be used as a potential novel therapeutic agent against liver fibrosis.<\/jats:p>","DOI":"10.3390\/bioengineering10091075","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T08:58:08Z","timestamp":1694422688000},"page":"1075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Isolation and Biological Evaluation of Alfa-Mangostin as Potential Therapeutic Agents against Liver Fibrosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9836-1503","authenticated-orcid":false,"given":"Yi-Jen","family":"Liao","sequence":"first","affiliation":[{"name":"School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Ya","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0327-0738","authenticated-orcid":false,"given":"Yuh-Ching","family":"Twu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9218-6532","authenticated-orcid":false,"given":"Fat-Moon","family":"Suk","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"},{"name":"Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Chieh","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ching","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Wei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ming","family":"Jhuang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Ruei","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Chia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Po","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chinese Culture University, Taipei 111, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-8815","authenticated-orcid":false,"given":"Ming-Hua","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Changhua University of Education, Changhua 500, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1021\/acs.jnatprod.2c00531","article-title":"Hypouricemic Actions of the Pericarp of Mangosteen In Vitro and In Vivo","volume":"86","author":"Niu","year":"2023","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1021\/jf5007352","article-title":"Hidden potential of tropical fruit waste components as a useful source of remedy for obesity","volume":"62","author":"Asyifah","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1021\/acsanm.2c00105","article-title":"Antioxidant \u03b1-Mangostin Coated Woven Polycaprolactone Nanofibrous Yarn Scaffold for Cardiac Tissue Repair","volume":"5","author":"Verma","year":"2022","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.fct.2007.09.096","article-title":"Anti-inflammatory activity of mangostins from Garcinia mangostana","volume":"46","author":"Chen","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1021\/np020546u","article-title":"Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines","volume":"66","author":"Matsumoto","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1021\/acs.molpharmaceut.7b00334","article-title":"Alpha-mangostin reverses multidrug resistance by attenuating the function of the multidrug resistance-linked ABCG2 transporter","volume":"14","author":"Wu","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.bbamem.2012.09.004","article-title":"Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting","volume":"1828","author":"Koh","year":"2013","journal-title":"Biochim. Biophys. Acta BBA Biomembr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10135","DOI":"10.1021\/acs.jmedchem.7b01348","article-title":"Semisynthesis and biological evaluation of xanthone amphiphilics as selective, highly potent antifungal agents to combat fungal resistance","volume":"60","author":"Lin","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1021\/acs.jmedchem.0c00060","article-title":"Discovery and optimization of \u03b1-mangostin derivatives as novel PDE4 inhibitors for the treatment of vascular dementia","volume":"63","author":"Liang","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9846","DOI":"10.1021\/acsomega.0c00057","article-title":"Effects of \u03b1-mangostin derivatives on the Alzheimer\u2019s disease model of rats and their mechanism: A combination of experimental study and computational systems pharmacology analysis","volume":"5","author":"Chen","year":"2020","journal-title":"ACS Omega"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/S0140-6736(08)60383-9","article-title":"Liver cirrhosis","volume":"371","author":"Schuppan","year":"2008","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/S0168-8278(02)00429-4","article-title":"Liver fibrosis\u2014From bench to bedside","volume":"38","author":"Friedman","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.bbadis.2012.11.002","article-title":"Extracellular matrix degradation in liver fibrosis: Biochemistry and regulation","volume":"1832","author":"Iredale","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1172\/JCI30542","article-title":"Models of liver fibrosis: Exploring the dynamic nature of inflammation and repair in a solid organ","volume":"117","author":"Iredale","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.bpg.2011.02.006","article-title":"Liver fibrogenic cells","volume":"25","author":"Forbes","year":"2011","journal-title":"Best Pract. Research. Clin. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.tox.2008.06.013","article-title":"Hepatic fibrosis\u2014Overview","volume":"254","author":"Friedman","year":"2008","journal-title":"Toxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.bpg.2011.02.005","article-title":"Mechanisms of hepatic fibrogenesis","volume":"25","author":"Lee","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrgastro.2012.114","article-title":"Hepatic stem cells and transforming growth factor beta in hepatocellular carcinoma","volume":"9","author":"Majumdar","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1136\/gut.2005.088690","article-title":"Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis","volume":"56","author":"Inagaki","year":"2007","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1524-475X.2009.00466.x","article-title":"Interactions between extracellular matrix and growth factors in wound healing","volume":"17","author":"Schultz","year":"2009","journal-title":"Wound Repair. Regen."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"G709","DOI":"10.1152\/ajpgi.00451.2010","article-title":"Therapeutic targets in liver fibrosis","volume":"300","author":"Fallowfield","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1053\/jhep.2002.32673","article-title":"Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-beta soluble receptor: Implications for antifibrotic therapy","volume":"35","author":"Yata","year":"2002","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cytogfr.2015.10.002","article-title":"The PDGF system and its antagonists in liver fibrosis","volume":"28","author":"Weiskirchen","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/labinvest.2009.77","article-title":"Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787\/ZK22258","volume":"89","author":"Liu","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1111\/liv.12638","article-title":"Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT\/mTOR\/p70S6K and TGFbeta\/Smad signalling pathways","volume":"35","author":"Li","year":"2015","journal-title":"Liver Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/hep.27332","article-title":"Hepatic inflammation and fibrosis: Functional links and key pathways","volume":"61","author":"Seki","year":"2015","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192543","DOI":"10.1155\/2010\/192543","article-title":"Toll-like receptor signaling and liver fibrosis","volume":"2010","author":"Aoyama","year":"2010","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1053\/jhep.2003.50182","article-title":"Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells","volume":"37","author":"Paik","year":"2003","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"167sr161","DOI":"10.1126\/scitranslmed.3004700","article-title":"Therapy for fibrotic diseases: Nearing the starting line","volume":"5","author":"Friedman","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.jhep.2011.04.008","article-title":"Targeted therapy of liver fibrosis\/cirrhosis and its complications","volume":"55","author":"Poelstra","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s10495-005-1055-4","article-title":"The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis","volume":"10","author":"Elsharkawy","year":"2005","journal-title":"Apoptosis Int. J. Program. Cell Death"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.3748\/wjg.v12.i12.1918","article-title":"Effects of interleukin-10 on activation and apoptosis of hepatic stellate cells in fibrotic rat liver","volume":"12","author":"Zhang","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.1080\/13880209.2016.1223143","article-title":"Quercetin stimulates mitochondrial apoptosis dependent on activation of endoplasmic reticulum stress in hepatic stellate cells","volume":"54","author":"He","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.3390\/molecules20011277","article-title":"Bisdemethoxycurcumin Induces apoptosis in activated hepatic stellate cells via cannabinoid receptor 2","volume":"20","author":"Lee","year":"2015","journal-title":"Molecules"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Twu, Y.C., Lee, T.S., Lin, Y.L., Hsu, S.M., Wang, Y.H., Liao, C.Y., Wang, C.K., Liang, Y.C., and Liao, Y.J. (2016). Niemann-Pick Type C2 Protein Mediates Hepatic Stellate Cells Activation by Regulating Free Cholesterol Accumulation. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071122"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.tibs.2016.01.001","article-title":"Mitochondrial Cristae: Where Beauty Meets Functionality","volume":"41","author":"Cogliati","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.bbamcr.2010.08.011","article-title":"Cell metabolism: An essential link between cell growth and apoptosis","volume":"1813","author":"Mason","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","first-page":"661","article-title":"The current economic burden of cirrhosis","volume":"7","author":"Neff","year":"2011","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-beta\/SMAD Pathway and Its Regulation in Hepatic Fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13374","DOI":"10.1074\/jbc.M409444200","article-title":"The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation","volume":"280","author":"Gabele","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1074\/jbc.M212927200","article-title":"The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression","volume":"278","author":"Reif","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/hep.510300406","article-title":"Extracellular signal-regulated kinase activation differentially regulates platelet-derived growth factor\u2019s actions in hepatic stellate cells, and is induced by in vivo liver injury in the rat","volume":"30","author":"Marra","year":"1999","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"G253","DOI":"10.1152\/ajpgi.00471.2012","article-title":"Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells","volume":"306","author":"Peng","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1038\/srep03470","article-title":"HS-173, a novel PI3K inhibitor, attenuates the activation of hepatic stellate cells in liver fibrosis","volume":"3","author":"Son","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/35037710","article-title":"The biochemistry of apoptosis","volume":"407","author":"Hengartner","year":"2000","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chen, M.F., Huang, S.J., Huang, C.C., Liu, P.S., Lin, K.I., Liu, C.W., Hsieh, W.C., Shiu, L.Y., and Chen, C.H. (2016). Saikosaponin d induces cell death through caspase-3-dependent, caspase-3-independent and mitochondrial pathways in mammalian hepatic stellate cells. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2599-0"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.7150\/ijms.62903","article-title":"Ferroptosis and Liver Fibrosis","volume":"18","author":"Pan","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1016\/j.biopha.2018.11.030","article-title":"Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway","volume":"109","author":"Kong","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"874408","DOI":"10.3389\/fphar.2022.874408","article-title":"New Drugs for Hepatic Fibrosis","volume":"13","author":"Shan","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s42003-023-04473-2","article-title":"Nanodrug rescues liver fibrosis via synergistic therapy with H2O2 depletion and Saikosaponin b1 sustained release","volume":"6","author":"Dong","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2147\/NSA.S243017","article-title":"Nanoparticle drug delivery systems for mangostin","volume":"13","author":"Wathoni","year":"2020","journal-title":"Nanotechnol. Sci. Appl."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/10\/9\/1075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:48:42Z","timestamp":1760129322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/10\/9\/1075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,11]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["bioengineering10091075"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering10091075","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,11]]}}}