Solasodine, a Natural Steroidal Alkaloid, Attenuates RANKL-Induced Osteoclastogenesis and Bone Resorption: A Study Based on Network Pharmacology and Experimental Validation.

Authors

Yiwei Jiang, Zhiyu Jin, Xiaoyi Ji, Maihuan Wang, Zhen Cao

Published in

Journal of cellular and molecular medicine. Volume 30. Issue 12. Pages e71253.

Abstract

Osteoporosis is characterized by excessive bone resorption driven by aberrant osteoclast activation. Solasodine (SOL), a natural steroidal alkaloid, has undefined roles in bone metabolism. This study investigated SOL's effects on RANKL-induced osteoclastogenesis and its underlying mechanisms. Pharmacological targets predicted via network pharmacology and validated by molecular docking identified 81 overlapping targets, which were primarily enriched in MAPK, NF-κB, and JAK-STAT pathways, confirming robust affinity between SOL and core targets including NFκB1, JAK1/2, and STAT3. In vitro, bone marrow-derived macrophages (BMMs) were stimulated with M-CSF and RANKL. Evaluation via TRAcP staining, F-actin immunofluorescence, and hydroxyapatite assays showed that SOL dose-dependently inhibited RANKL-induced osteoclast formation, fusion, and resorptive activity without cytotoxicity. Mechanistic investigations through RT-qPCR, Western blotting, luciferase assays, ROS detection, and live-cell calcium monitoring revealed that SOL suppressed key markers, including NFATc1, c-Fos, CTSK, Atp6v0d2, and Integrin β3. Specifically, SOL attenuated MAPK (p38, JNK, ERK) and STAT3 phosphorylation, inhibited NF-κB activity, and prevented IκB-α degradation. Furthermore, SOL curtailed RANKL-induced ROS generation, intracellular calcium oscillations, and subsequent CaMKIV activation. Ultimately, SOL inhibits RANKL-induced osteoclastogenesis and bone resorption by suppressing the NFATc1/c-Fos axis through coordinated modulation of the MAPK, NF-κB, and JAK-STAT pathways, alongside mitigation of ROS production and calcium signalling, representing a promising natural candidate for treating osteolytic bone diseases.

PMID:
42322165
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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