Exploring the Potential Effects of Tinospora crispa Extracts on RAGE Expression, Cytokine Modulation, and Cell Morphology in Methylglyoxal-Induced Osteoblast Inflammation

• Main Author: Teknowilie, Anak Singa
• Format: Thesis
• Language: English; English
• Published: Unpublished 2025
• Subjects: Q Science (General); RB Pathology; RM Therapeutics. Pharmacology
• Online Access: http://ir.unimas.my/id/eprint/49035/

High blood sugar levels are the primary cause of type 2 diabetes mellitus (T2DM), a complex illness in which bone loss is a major but frequently disregarded consequences. One contributing factor is the formation of advanced glycation end products (AGE), where compounds like methylglyoxal (MGO) react with proteins, impairing their function and causing oxidative stress. This process accelerates tissue damage in uncontrolled diabetes due to prolonged high blood sugar and oxidative stress, thus contributing to diabetic bone loss. Despite T. crispa’s established anti-hyperglycaemic properties, its role in mitigating MGO-induced bone disorders is poorly understood. This study explored the antioxidant, anti-inflammatory, and anti-glycation properties of T. crispa water (TiW) and methanol (TiM) extracts, alone or combined with metformin, in MGO-stimulated hFOB 1.19 osteoblast cells. Phytochemical screening, GC-MS, FRAP, and BSA-MGO assays evaluated the extracts’ active compounds and properties. Cell viability assays identified non-toxic doses (>80%) for TiW (3000 μg/mL) and TiM (476 μg/mL). Luminex assays and ELISAs measured inflammatory markers (IL-1β, IL-6, M-CSF), RAGE components (flRAGE, sRAGE), and RANKL, while cell morphology was assessed for structural changes. Results showed that TiW (3000 μg/mL) and TiM (476 μg/mL) significantly reduced IL-1β levels. Additionally, TiM (238 μg/mL and 476 μg/mL) combined with metformin lowered IL-1β and IL-6 to undetectable levels, indicating synergistic effects. TiW increased sRAGE concentrations, suggesting reduced AGE binding and inflammation, while TiM exhibited varied effects on M-CSF levels. TiW combined with metformin significantly reduced flRAGE levels, supporting a synergistic effect. Morphometric analysis revealed TiM (238 μg/mL) with metformin mitigated MGO-induced cell damage, preserving cell health and structure. In conclusion, T. crispa extracts, particularly in combination with metformin, exhibit promising anti-inflammatory, antioxidative, and anti-glycation properties. These findings highlight the potential of T. crispa in preventing T2DM-associated bone loss by modulating inflammatory pathways, reducing AGE-RAGE interactions, and preserving osteoblast integrity.