{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:59:08Z","timestamp":1760147948347,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174083","2022NSFSC1735","ZYN2022094"],"award-info":[{"award-number":["82174083","2022NSFSC1735","ZYN2022094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["82174083","2022NSFSC1735","ZYN2022094"],"award-info":[{"award-number":["82174083","2022NSFSC1735","ZYN2022094"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["82174083","2022NSFSC1735","ZYN2022094"],"award-info":[{"award-number":["82174083","2022NSFSC1735","ZYN2022094"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to alleviate acute liver injury (ALI). Herpetfluorenone (HPF), as an active ingredient in the dried, mature seeds Herpetospermum caudigerum Wall, used in Tibetan medicine, has been proven to effectively alleviate ALI. Therefore, the purpose of this study was to determine whether HPF can promote the differentiation of BMSCs into HLCs and promote ALI recovery. Mouse BMSCs were isolated, and the BMSCs\u2019 differentiation into HLCs was induced by HPF and hepatocyte growth factor (HGF). Under the induction of HPF and HGF, the expression of hepatocellular specific markers and the accumulation of glycogen and lipids in the BMSCs increased, indicating that BMSCs successfully differentiated into HLCs. Then, the ALI mouse model was established, using carbon tetrachloride, followed by an intravenous injection of BMSCs. Then, only HPF was injected intraperitoneally, in order to verify the effect of HPF in vivo. In vivo imaging was used to detect the homing ability of HPF\u2013BMSCs, and it was detected that HPF\u2013BMSCs significantly increased the levels of serum AST, ALT and ALP in the liver of ALI mice, and alleviated liver cell necrosis, oxidative stress and liver pathology. In conclusion, HPF can promote the differentiation of BMSCs into HLCs and promote the recovery of ALI in mice.<\/jats:p>","DOI":"10.3390\/ijms24065686","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T03:33:57Z","timestamp":1679024037000},"page":"5686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["HPF Modulates the Differentiation of BMSCs into HLCs and Promotes the Recovery of Acute Liver Injury in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Bin","family":"Yang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-Lin","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maimaitituxun","family":"Maierziya","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Southwest Minzu University, Chengdu 610225, China"},{"name":"BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.jhep.2014.10.022","article-title":"Role for the endoplasmic reticulum stress sensor IRE1\u03b1 in liver regenerative responses","volume":"62","author":"Liu","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e22470","DOI":"10.1002\/jbt.22470","article-title":"Hepatoprotective effect of allicin against acetaminophen-induced liver injury: Role of inflammasome pathway, apoptosis, and liver regeneration","volume":"34","author":"Samra","year":"2020","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1111\/j.1478-3231.2010.02262.x","article-title":"Acute liver failure: Mechanisms of immune-mediated liver injury","volume":"30","author":"Wu","year":"2010","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"966759","DOI":"10.3389\/fphar.2022.966759","article-title":"Mechanism of hydroxysafflor yellow A on acute liver injury based on transcriptomics","volume":"13","author":"Hou","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s40268-020-00333-0","article-title":"Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment","volume":"21","author":"Marra","year":"2021","journal-title":"Drugs R D"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.jhep.2013.04.003","article-title":"Immunosuppression minimization vs. complete drug withdrawal in liver trans-plantation","volume":"59","author":"Rimola","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14716","DOI":"10.1021\/acsami.7b02805","article-title":"Mesenchymal Stem Cell-Seeded Regenerated Silk Fibroin Complex Matrices for Liver Regeneration in an Animal Model of Acute Liver Failure","volume":"9","author":"Xu","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.molmed.2015.09.004","article-title":"The Therapeutic Promise of Mesenchymal Stem Cells for Liver Restoration","volume":"21","author":"Christ","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41420-022-00850-8","article-title":"Long noncoding RNA SNHG1 silencing accelerates hepatocyte-like cell differentiation of bone mar-row-derived mesenchymal stem cells to alleviate cirrhosis via the microRNA-15a\/SMURF1\/UVRAG axis","volume":"8","author":"Sun","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_10","first-page":"187","article-title":"Bone Marrow Mesenchymal Stem Cells Reverse Liver Damage in a Carbon Tetrachlo-ride-induced Mouse Model of Chronic Liver Injury","volume":"30","author":"Wang","year":"2016","journal-title":"In Vivo"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13287-020-01655-1","article-title":"Ultrasound-targeted microbubble destruction optimized HGF-overexpressing bone marrow stem cells to repair fibrotic liver in rats","volume":"11","author":"Sun","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/hep.25722","article-title":"Immediate intraportal transplantation of human bone marrow mesenchymal stem cells prevents death from fulminant hepatic failure in pigs","volume":"56","author":"Li","year":"2012","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.15283\/ijsc.2014.7.2.49","article-title":"Concise Review: Differentiation of Human Adult Stem Cells Into Hepatocyte-like Cells In vitro","volume":"7","author":"Zhang","year":"2014","journal-title":"Int. J. Stem Cells"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/cbin.10630","article-title":"Hepatocyte growth factor-induced differentiation of bone mesenchymal stem cells toward hepatocyte-like cells occurs through nuclear factor-kappa B signaling in vitro","volume":"40","author":"Yang","year":"2016","journal-title":"Cell Biol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nejak-Bowen, K., Orr, A., Bowen, W.C., and Michalopoulos, G.K. (2013). Conditional Genetic Elimination of Hepatocyte Growth Factor in Mice Compromises Liver Regeneration after Partial Hepatectomy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059836"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3892\/mmr.2016.6083","article-title":"Effect of Yi Guan Jian decoction on differentiation of bone marrow mesenchymalstem cells into hepatocyte-like cells in dimethylnitrosamine-induced liver cirrhosis in mice","volume":"15","author":"Xiang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1211\/jpp.62.04.0017","article-title":"In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced by salidroside","volume":"62","author":"Ouyang","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gong, P.-Y., Yuan, Z.-X., Gu, J., Tan, R., Li, J.-C., Ren, Y., and Hu, S. (2016). Anti-HBV Activities of Three Compounds Extracted and Purified from Herpetospermum Seeds. Molecules, 22.","DOI":"10.3390\/molecules22010014"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.biotechadv.2014.01.003","article-title":"Pluripotent stem cell-derived hepatocyte-like cells","volume":"32","author":"Schwartz","year":"2014","journal-title":"Biotechnol. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1517\/17425255.1.1.61","article-title":"Generation of human hepatocytes by stem cell technology: Definition of the hepatocyte","volume":"1","author":"Hengstler","year":"2005","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000380762","article-title":"Induction of Functional Hepatocyte-Like Cells by Overexpression of FOXA3 and HNF4\u03b1 in Rat Bone Marrow Mesenchymal Stem Cells","volume":"200","author":"Dai","year":"2014","journal-title":"Cells Tissues Organs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101312","DOI":"10.1016\/j.tice.2019.101312","article-title":"Down-regulation of SOX17, GATA4 and FoxA2 promotes differentiation potential of hepatocytes from human hematopoietic stem cells","volume":"62","author":"Kumar","year":"2020","journal-title":"Tissue Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.ultrasmedbio.2018.01.005","article-title":"Ultrasound Irradiation Combined with Hepatocyte Growth Factor Accelerate the Hepatic Differentiation of Human Bone Marrow Mesenchymal Stem Cells","volume":"44","author":"Li","year":"2018","journal-title":"Ultrasound Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.bbrc.2004.05.213","article-title":"Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction","volume":"320","author":"Wang","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13093","DOI":"10.1021\/acs.jafc.1c05411","article-title":"A Novel Sialoglycopeptide from Gadus morhua Eggs Prevents Liver Fibrosis Induced by CCl4 via Downregulating FXR\/FGF15 and TLR4\/TGF-\u03b2\/Smad Pathways","volume":"69","author":"Yue","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114058","DOI":"10.1016\/j.bcp.2020.114058","article-title":"Celastrol ameliorates acute liver injury through modulation of PPAR\u03b1","volume":"178","author":"Zhao","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, R., Yang, Z., Zhang, J., Mu, J., Zhou, X., and Zhao, X. (2019). Liver Injury Induced by Carbon Tetrachloride in Mice Is Prevented by the Antioxidant Capacity of Anji White Tea Polyphenols. Antioxidants, 8.","DOI":"10.3390\/antiox8030064"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5686\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:56:38Z","timestamp":1760122598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,16]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065686"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065686","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,3,16]]}}}