{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:19:56Z","timestamp":1785755996538,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T00:00:00Z","timestamp":1564790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiation-induced oral mucositis represents an influential factor in cancer patients\u2019 accepted radiation therapy, especially in head and neck cancer. This research investigates the treatment effect of Ecdysterone (a steroid derived from the dry root of Achyranthes bidentate) and Paeonol (a compound derived from Cortex Moutan) on radiation-induced oral mucositis and possible underlying mechanisms. Concisely, 20 Gy of X-rays (single-dose) irradiated the cranial localization in rats for the modeling of oral mucositis. The therapeutic effects of Ecdysterone-Paeonol oral cavity directly administered on radiation-induced oral mucositis were investigated by weight changes, direct observations, visual scoring methods, ulcer area\/total area, and basic recovery days. Assessments of tumor necrosis factor \u03b1 and interleukin-6 were performed to evaluate the inflammatory cytokines secretion in the damaged areas of tongues harvested post-treatment, and changes in signaling pathways were investigated by Western blotting. System Drug Target (SysDT) methods revealed the targets of Ecdysterone-Paeonol in order to support compound-target network construction. Four representative targets with different functions were chosen. The binding interactions between the compound and receptor were evaluated by molecular docking to investigate the binding affinity of the ligand to their protein targets. Ecdysterone-Paeonol, administered orally, effectively improved radiation-induced oral mucositis in rats, and the therapeutic effect was better than Ecdysterone administered orally on its own. In this study, calculational chemistry revealed that Ecdysterone-Paeonol affected 19 function targets associated with radiation-induced oral mucositis, including apoptosis, proliferation, inflammation, and wound healing. These findings position Ecdysterone-Paeonol as a potential treatment candidate for oral mucositis acting on multiple targets in the clinic.<\/jats:p>","DOI":"10.3390\/ijms20153800","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T03:25:22Z","timestamp":1564975522000},"page":"3800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Therapeutic Effect of Ecdysterone Combine Paeonol Oral Cavity Direct Administered on Radiation-Induced Oral Mucositis in Rats"],"prefix":"10.3390","volume":"20","author":[{"given":"Li","family":"Yang","sequence":"first","affiliation":[{"name":"School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.ijrobp.2007.01.053","article-title":"Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies","volume":"68","author":"Elting","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cden.2017.08.010","article-title":"Dental Management of Patients Who Have Undergone Oral Cancer Therapy","volume":"62","author":"Villa","year":"2018","journal-title":"Dent Clin. North. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3389\/fonc.2017.00089","article-title":"Radiation-Induced Oral Mucositis","volume":"7","author":"Maria","year":"2017","journal-title":"Front Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1601-0825.2006.01258.x","article-title":"Oral mucositis","volume":"12","author":"Scully","year":"2006","journal-title":"Oral Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s40496-015-0069-4","article-title":"Oral Mucositis Induced By Anticancer Therapies","volume":"2","author":"Zecha","year":"2015","journal-title":"Curr. Oral Health Rep."},{"key":"ref_6","first-page":"3","article-title":"Pathobiology of oral mucositis: Novel insights and opportunities","volume":"5","author":"Sonis","year":"2007","journal-title":"J. Support Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"837513","DOI":"10.1155\/2012\/837513","article-title":"Anti-inflammatory and anticoagulative effects of paeonol on LPS-induced acute lung injury in rats. Evid Based Complement","volume":"2012","author":"Fu","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/sj.bjp.0705360","article-title":"Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia","volume":"139","author":"Chou","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","first-page":"1603","article-title":"Transdermal delivery of paeonol using cubic gel and microemulsion gel","volume":"6","author":"Luo","year":"2011","journal-title":"Int. J. Nanomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1055\/s-0028-1088332","article-title":"Paeonol attenuates high-fat-diet-induced atherosclerosis in rabbits by anti-inflammatory activity","volume":"75","author":"Li","year":"2009","journal-title":"Planta Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1080\/21691401.2019.1613418","article-title":"Paeonol prevents IL-1beta-induced inflammatory response and degradation of type II collagen in human primary chondrocytes","volume":"47","author":"Wang","year":"2019","journal-title":"Artif Cells Nanomed. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yu, H., Chen, J., Xu, X., Li, Y., Zhao, H., Fang, Y., Li, X., Zhou, W., Wang, W., and Wang, Y. (2012). A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037608"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1101\/gad.1165804","article-title":"Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta","volume":"18","author":"Qu","year":"2004","journal-title":"Genes. Dev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Papareddy, P., Rydengard, V., Pasupuleti, M., Walse, B., Morgelin, M., Chalupka, A., Malmsten, M., and Schmidtchen, A. (2010). Proteolysis of human thrombin generates novel host defense peptides. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000857"},{"key":"ref_15","first-page":"65","article-title":"Synthetic peptides bind to high-affinity thrombin receptors and modulate thrombin mitogenesis","volume":"1","author":"Glenn","year":"1988","journal-title":"Pept. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Spalinger, M.R., Lang, S., Vavricka, S.R., Fried, M., Rogler, G., and Scharl, M. (2013). Protein tyrosine phosphatase non-receptor type 22 modulates NOD2-induced cytokine release and autophagy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072384"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Brief Bioinform."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1021\/acs.molpharmaceut.7b00505","article-title":"Systems Pharmacology Dissection of Multiscale Mechanisms of Action for Herbal Medicines in Treating Rheumatoid Arthritis","volume":"14","author":"Wang","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1021\/acs.jafc.6b01067","article-title":"Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors","volume":"64","author":"Wang","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, Y., Wang, J., Sun, K., Tao, W., Wang, Z., Xiao, W., Pan, Y., Zhang, S., and Wang, Y. (2017). Systematic Investigation of Ginkgo Biloba Leaves for Treating Cardio-cerebrovascular Diseases in an Animal Model. Acs Chem. Biol., 12.","DOI":"10.1021\/acschembio.6b00762"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4103\/jmp.JMP_78_17","article-title":"A Treatment Planning Method for Better Management of Radiation-Induced Oral Mucositis in Locally Advanced Head and Neck Cancer","volume":"43","author":"Zhang","year":"2018","journal-title":"J. Med. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.oraloncology.2009.08.006","article-title":"Mucositis: The impact, biology and therapeutic opportunities of oral mucositis","volume":"45","author":"Sonis","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00520-006-0056-3","article-title":"Mucositis guidelines: What have they achieved, and where to from here?","volume":"14","author":"Keefe","year":"2006","journal-title":"Support Care Cancer."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3322\/canjclin.51.5.290","article-title":"Oral mucositis complicating chemotherapy and\/or radiotherapy: Options for prevention and treatment","volume":"51","author":"Kostler","year":"2001","journal-title":"CA Cancer J. Clin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1634\/stemcells.2007-0197","article-title":"Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing","volume":"25","author":"Chamberlain","year":"2007","journal-title":"Stem Cells."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.etap.2018.04.016","article-title":"Paeonol alleviated acute alcohol-induced liver injury via SIRT1\/Nrf2\/NF-kappaB signaling pathway","volume":"60","author":"Sun","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.intimp.2003.12.013","article-title":"Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-alpha","volume":"4","author":"Kim","year":"2004","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fphar.2018.00095","article-title":"Paeonol Inhibits Oxidized Low-Density Lipoprotein-Induced Vascular Endothelial Cells Autophagy by Upregulating the Expression of miRNA-30a","volume":"9","author":"Li","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, Y., Zhou, W., Chen, Y., Wu, Q., Pan, Y., Zhang, S., and Yang, L. (2018). Exploring the structural determinants of novel xanthine derivatives as A2B adenosine receptor antagonists: A computational study. J. Biomol. Struct. Dyn., 1\u201315.","DOI":"10.1080\/07391102.2018.1517612"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/s41598-017-01613-7","article-title":"A New Strategy for Deleting Animal drugs from Traditional Chinese Medicines based on Modified Yimusake Formula","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fphar.2011.00010","article-title":"Anti-inflammatory and immunomodulatory effects of paeonia lactiflora pall., a traditional chinese herbal medicine","volume":"2","author":"He","year":"2011","journal-title":"Front. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1667\/RR15171.1","article-title":"Ecdysterone Accelerates Healing of Radiation-Induced Oral Mucositis in Rats by Increasing Matrix Cell Proliferation","volume":"191","author":"Li","year":"2019","journal-title":"Radiat. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome. Res."},{"key":"ref_34","first-page":"8","article-title":"Using AutoDock for ligand-receptor docking","volume":"8","author":"Morris","year":"2008","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1021\/ci800063v","article-title":"Molecular docking of intercalators and groove-binders to nucleic acids using Autodock and Surflex","volume":"48","author":"Holt","year":"2008","journal-title":"J. Chem. Inf. Model."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:13:09Z","timestamp":1760188389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,3]]},"references-count":35,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20153800"],"URL":"https:\/\/doi.org\/10.3390\/ijms20153800","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,3]]}}}