Therapeutic Effect of Ecdysterone Combine Paeonol Oral Cavity Direct Administered on Radiation-Induced Oral Mucositis in Rats

• Published in: International journal of molecular sciences Vol. 20; no. 15; p. 3800
• Main Authors: Yang, Li, Pan, Jian
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.08.2019; MDPI
• Subjects: Abnormalities, Radiation-Induced - drug therapy; Abnormalities, Radiation-Induced - pathology; Acetophenones - pharmacology; Animals; Anti-inflammatory agents; Apoptosis; Apoptosis - drug effects; autodock; Binding sites; Cancer therapies; Cell growth; compound-target network; Cytokines; Disease Models, Animal; Drug Combinations; Ecdysterone - pharmacology; ecdysterone-paeonol; Economic conditions; Economic impact; Head & neck cancer; Humans; Inflammation; Kinases; Ligands; Molecular Docking Simulation; Mouth - drug effects; Mouth - pathology; Mucositis; Oral cavity; oral cavity direct administered; Pharmacology; Proteins; Quality of life; Radiation effects; Radiation Injuries - drug therapy; Radiation Injuries - etiology; Radiation Injuries - pathology; Radiation therapy; radiation-induced oral mucositis; Rats; Signal Transduction - drug effects; Stomatitis - drug therapy; Stomatitis - etiology; Stomatitis - pathology; therapeutic effect; Wound healing; therapeutic effect; autodock; oral cavity direct administered; radiation-induced oral mucositis; ecdysterone-paeonol; compound-target network
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20153800

Radiation-induced oral mucositis represents an influential factor in cancer patients' 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 ) and Paeonol (a compound derived from ) 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 α 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.