Abstract
OBJECTIVES: This study investigated the therapeutic effects of stigmasterol (STG), derived from Cornus officinalis, on osteoporosis in rats with type 2 diabetes mellitus (T2DM). METHODS: Twenty-four Male Sprague-Dawley rats (6 weeks old) were used to establish a T2DM model and were divided into four groups: normal diet (ND), high-fat diet (HFD), low-dose STG (STG-L, 100 mg/kg), and high-dose STG (STG-H, 200 mg/kg). The rats received daily gavage treatments for four weeks. Therapeutic effects were assessed by examining femoral bone structure, serum bone formation markers (P1NP, osteocalcin, and osteoprotegerin), bone resorption indices (CTX-1 and RANKL), and osteogenic protein expression (Runx2, osteopontin, and COL1A1). RESULTS: STG significantly reduced fasting blood glucose levels and improved insulin resistance in T2DM rats. It enhanced trabecular bone microstructure, with the STG-H group demonstrating superior effects. Compared to the HFD group, STG increased bone mineral density, bone volume fraction (BV/TV), and trabecular thickness, while reducing bone surface-to-volume ratio (BS/BV) and trabecular separation. STG also elevated serum levels of P1NP, osteocalcin, and osteoprotegerin, while reducing CTX-1 and RANKL. Western blot analysis revealed increased expression of Runx2, osteopontin, and COL1A1 in femoral tissues. CONCLUSIONS: STG appears to alleviate osteoporosis in diabetes by improving bone microstructure, promoting bone formation, and reducing bone resorption, indicating its potential as a therapeutic option for managing osteoporosis.