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

Zhang, Lifang; Deepak, Vishwa

doi:10.3390/ijms27083578

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

by

Lifang Zhang

^1,2

and

Vishwa Deepak

^{1,2,3,4,5,6,*}

¹

Osteoimmunology and Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China

²

Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ 07083, USA

³

International Frontier Interdisciplinary Research Institute (IFIRI), Wenzhou-Kean University, Wenzhou 325060, China

⁴

Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Ouhai, Wenzhou 325060, China

⁵

Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Ouhai, Wenzhou 325060, China

⁶

Zhejiang-Malaysia Joint Laboratory for Rare Medicinal Resources, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou 325060, China

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(8), 3578; https://doi.org/10.3390/ijms27083578

Submission received: 7 March 2026 / Revised: 7 April 2026 / Accepted: 10 April 2026 / Published: 17 April 2026

(This article belongs to the Special Issue New Insights into Osteoclasts)

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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 receptor activator of nuclear factor kappa-B ligand (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 μM. Our mechanistic investigations revealed that 8-Epixanthatin interferes with RANKL-activated signaling networks, particularly nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) cascades. Collectively, these observations identify 8-Epixanthatin as a promising lead structure for anti-osteoclast drug discovery.

Keywords: osteoclast differentiation; receptor activator of nuclear factor kappa-B ligand (RANKL); nuclear factor κB (NF-κB); mitogen-activated protein kinase (MAPK); osteoporosis; bone resorption; natural compounds

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MDPI and ACS Style

Zhang, L.; Deepak, V. 8-Epixanthatin Suppresses RANKL-Induced Osteoclast Differentiation via Inhibition of NF-κB and MAPK Signaling. Int. J. Mol. Sci. 2026, 27, 3578. https://doi.org/10.3390/ijms27083578

AMA Style

Zhang L, Deepak V. 8-Epixanthatin Suppresses RANKL-Induced Osteoclast Differentiation via Inhibition of NF-κB and MAPK Signaling. International Journal of Molecular Sciences. 2026; 27(8):3578. https://doi.org/10.3390/ijms27083578

Chicago/Turabian Style

Zhang, Lifang, and Vishwa Deepak. 2026. "8-Epixanthatin Suppresses RANKL-Induced Osteoclast Differentiation via Inhibition of NF-κB and MAPK Signaling" International Journal of Molecular Sciences 27, no. 8: 3578. https://doi.org/10.3390/ijms27083578

APA Style

Zhang, L., & Deepak, V. (2026). 8-Epixanthatin Suppresses RANKL-Induced Osteoclast Differentiation via Inhibition of NF-κB and MAPK Signaling. International Journal of Molecular Sciences, 27(8), 3578. https://doi.org/10.3390/ijms27083578

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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

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