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8-Epixanthatin Suppresses RANKL-Induced Osteoclast Differentiation via Inhibition of NF-κB and MAPK Signaling

Zhang, L.; Deepak, V.

2026-01-14 pharmacology and toxicology
10.64898/2026.01.13.699384 bioRxiv
Show abstract

Osteoclast hyperactivity represents a central mechanism in pathological bone destruction, underscoring the importance of discovering novel anti-resorptive compounds. In this study, we present early-stage evidence that 8-Epixanthatin can inhibit osteoclast differentiation induced by RANKL. 8-Epixanthatin exhibited no significant cytotoxicity at the concentrations used for osteoclast differentiation studies. The compound showed concentration-dependent reductions in TRAP-positive multinucleated osteoclasts, with an IC50 value of 2.3 M. Our mechanistic investigations revealed that 8-Epixanthatin interferes with RANKL-activated signaling networks, particularly NF-{kappa}B and MAPK cascades. Collectively, these observations identify 8-Epixanthatin as a promising lead structure for anti-osteoclast drug discovery.

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