Xenobiotica; the fate of foreign compounds in biological systems · 2025
In vitro anti-glucocorticoid osteoporosis effect of Serfurosterone A and its intestinal absorption characteristics.
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Dong Jiaojiao, Yang Lin, Xue Jinhao, Gao Shiwen, Sun Yanping, Zhang Xiaojuan, Yang Liu
Аннотация
OBJECTIVE: This study evaluated the effects of Serfurosterone A (SSA) from Achyranthes bidentata Bl. on dexamethasone (DEX)-induced osteoblast dysfunction and its intestinal permeability.
METHODS: The anti-osteoporotic effects of SSA were assessed by MTT assay, flow cytometry, osteogenic differentiation induction, and western blotting. Intestinal permeability and transport mechanisms were investigated using Caco-2 cell models and single-pass intestinal perfusion (SPIP) in rats.
RESULTS: SSA (5-50 µM) increased the viability and proliferation of DEX-injured MC3T3-E1 cells, enhanced alkaline phosphatase (ALP) activity, and promoted mineralized nodule formation. Western blot analysis suggested that SSA's effects may involve activation of the Wnt/β-catenin signaling pathway, characterized by upregulation of β-catenin and downregulation of GSK3β. In the Caco-2 assays, SSA showed moderate absorption (Papp 1.551-2.443 × 10-6 cm/s; ER 0.751-0.898) via passive transcellular transport. SPIP experiments further indicated efficient absorption across all intestinal segments (Peff > 2 × 10-5 cm/s), with the duodenum as the main absorption site.
CONCLUSIONS: SSA mitigates DEX-induced osteogenic inhibition and exhibits favorable intestinal absorption, suggesting its potential as a promising oral candidate for glucocorticoid-induced osteoporosis (GIOP). These results underscore the therapeutic promise of Achyranthes-derived phytosterols for future drug development.
METHODS: The anti-osteoporotic effects of SSA were assessed by MTT assay, flow cytometry, osteogenic differentiation induction, and western blotting. Intestinal permeability and transport mechanisms were investigated using Caco-2 cell models and single-pass intestinal perfusion (SPIP) in rats.
RESULTS: SSA (5-50 µM) increased the viability and proliferation of DEX-injured MC3T3-E1 cells, enhanced alkaline phosphatase (ALP) activity, and promoted mineralized nodule formation. Western blot analysis suggested that SSA's effects may involve activation of the Wnt/β-catenin signaling pathway, characterized by upregulation of β-catenin and downregulation of GSK3β. In the Caco-2 assays, SSA showed moderate absorption (Papp 1.551-2.443 × 10-6 cm/s; ER 0.751-0.898) via passive transcellular transport. SPIP experiments further indicated efficient absorption across all intestinal segments (Peff > 2 × 10-5 cm/s), with the duodenum as the main absorption site.
CONCLUSIONS: SSA mitigates DEX-induced osteogenic inhibition and exhibits favorable intestinal absorption, suggesting its potential as a promising oral candidate for glucocorticoid-induced osteoporosis (GIOP). These results underscore the therapeutic promise of Achyranthes-derived phytosterols for future drug development.