BACKGROUND: Acanthopanax senticosus (Rupr. et Maxim.) is commonly used in Traditional Chinese Medicine. Syringin is a major ingredient of phenolic glycoside in Acanthopanax senticosus. OBJECTIVE: This study was performed to investigate whether Syringin could protect high glucose-induced bone marrow mesenchymal stem cells (BMSCs) injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling. METHODS: BMSCs isolated from both the tibia and femur of mice were induced for osteogenesis. The cell senescence was induced using the high glucose medium. The cells were treated with 10 and 100 μmol/l Syringin. Immunohistochemistry staining was performed to determine the β-galactosidase (SA-β-gal) levels in differentially treated BMSCs. MTT assay and flow cytometry analysis were also performed to assess cell viability and cell cycle. The level of ROS in cells with different treatment was measured by using flow cytometry with DCF-DA staining. Calcium deposition and mineralized matrices were detected with alizarin red and ALP staining, respectively. Osteogenesis related genes OCN, ALP, Runx2, and BMP-2 were detected by RT-PCR. Levels of senescence-related proteins including p53 and p21, as well as JAK2, p-JAK2, STAT3, and p-STAT3 were detected by Western blot analysis. RESULTS: Syringin treatment reversed the phenotypes of senescence caused by high glucose in BMSCs, including the arrest of G0/G1 cell cycle, enhanced SA-β-gal activity, and impaired cell growth. Syringin also decreased the elevated ROS production and the levels of p53, p21, and JAK2/STAT3 signaling activation. In addition, Syringin also enhanced the osteogenic potential determined by ARS and ALP staining, as well as increasing OCN, ALP, Runx2, and BMP-2 expressions. CONCLUSION: Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.
- MeSH
- Phenylpropionates pharmacology MeSH
- Glucose * metabolism toxicity MeSH
- Glucosides * pharmacology MeSH
- Janus Kinase 2 * metabolism MeSH
- Mesenchymal Stem Cells * drug effects metabolism MeSH
- Mice MeSH
- Osteogenesis * drug effects MeSH
- Osteoporosis * prevention & control metabolism chemically induced pathology drug therapy MeSH
- Reactive Oxygen Species metabolism MeSH
- Signal Transduction * drug effects MeSH
- Cellular Senescence * drug effects MeSH
- STAT3 Transcription Factor * metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Roxadustat (RXD) is an approved drug substances for the treatment of renal anemia. It has poor aqueous solubility and photochemical stability. This study employs a comprehensive approach to enhance the stability and physicochemical properties RXD through coformer selection and characterization. The investigation integrates delta pKa analysis, molecular complementary assessment, molecular electrostatic potential surface analysis, and machine learning techniques to predict potential co-crystal formation and binding interactions between drug molecules and coformers. The co-crystal screening which lead to in a novel RXD-nicotinamide co-crystal (RXD-NA). Experimental characterization underscores the physical and chemical stability of the co-crystals. To elucidate the supramolecular synthons and understand the intermolecular interactions in the RXD-NA co-crystal, Hirshfeld surfaces analysis, quantum theory of atoms in molecules (QTAIM) analysis and non-covalent interaction (NCI) analysis were performed. Computational analysis of photo-isomer formation aligns with experimental observations, further enhancing our understanding of RXD-coformer interactions. RXD-NA co-crystal was found photo-chemically stable as compared to free base API drug substance. This integrated methodology provides a systematic framework for informed co-crystal design, holding promise for optimizing RXD formulations based on molecular interactions and stability considerations. Consequently, this study contributes valuable insights to the field of rational drug design and formulation optimization.
- MeSH
- Glycine * MeSH
- Solubility MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Humans MeSH
- Insurance Carriers MeSH
- Health Care Reform MeSH
- Child Health Services * organization & administration legislation & jurisprudence MeSH
- Emergency Service, Hospital * organization & administration legislation & jurisprudence MeSH
- Quality Assurance, Health Care MeSH
- Legislation, Medical MeSH
- Legislation, Hospital MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
- MeSH
- Ambulatory Care Facilities organization & administration MeSH
- Health Services Accessibility * MeSH
- Cardiac Care Facilities * organization & administration MeSH
- Cardiovascular Diseases prevention & control MeSH
- Humans MeSH
- Medically Underserved Area MeSH
- Primary Prevention MeSH
- Regional Health Planning MeSH
- Insurance, Health, Reimbursement MeSH
- Quality Assurance, Health Care MeSH
- Health Policy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
- MeSH
- Health Care Costs legislation & jurisprudence MeSH
- General Practice economics legislation & jurisprudence MeSH
- Primary Health Care economics legislation & jurisprudence MeSH
- Health Care Reform * legislation & jurisprudence MeSH
- Strikes, Employee MeSH
- Insurance, Health, Reimbursement * legislation & jurisprudence MeSH
- Legislation as Topic MeSH
- Publication type
- Newspaper Article MeSH
- Interview MeSH
