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Phytomedicine. 2019 Jun;59:152910. doi: 10.1016/j.phymed.2019.152910. Epub 2019 Apr 2.

Longan fruit increase bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation.

Author information

1
Department of Bio and Fermentation Convergence Technology, BK21PLUS Program, Kookmin University, Seoul 02707, Republic of Korea.
2
Department of Food Science and Biotechnology, CHA University, Seongnam 13488, Republic of Korea. Electronic address: foodguy@cha.ac.kr.
3
Department of Bio and Fermentation Convergence Technology, BK21PLUS Program, Kookmin University, Seoul 02707, Republic of Korea. Electronic address: ohsa@kookmin.ac.kr.

Abstract

BACKGROUND:

The receptor activator of nuclear factor-kappa B ligand (RANKL)-induced nuclear factor-kappa B (NF-κB) signaling pathway plays essential roles in osteoclast differentiation and may serve as an attractive target for the development of therapeutics for osteoporosis.

PURPOSE:

This study aimed to identify plant extracts that attenuated RANKL-induced NF-κB signaling pathway and examine their anti-osteoporotic effects in animal model systems.

METHODS:

Osteoclast differentiation was determined by western blot analysis, RT-PCR, and tartrate-resistant acid phosphatase (TRAP) assay. The effect of Longan (Dimocarpus longan Lour.) fruit extract (LFE) on bone mineral density was evaluated by calcein staining in zebrafish and micro-CT analysis in ovariectomized (OVX) rat.

RESULTS:

LFE nullified RANKL-induced down-regulation of inhibitor of NF-κB, which keeps NF-κB sequestered in the cytosol, thereby inhibiting translocation of NF-κB to the nucleus, in RAW264.7 cells. In addition, LFE decreased the nuclear levels of c-Fos and nuclear factor of activated T-cells c1, which play crucial roles in RANKL-induced osteoclast differentiation, in RAW264.7 cells. LFE repressed RANKL-activated cathepsin K and TRAP expression in RAW264.7 cells, resulting in a reduction of the number of TRAP-positive multinucleated cells, without cytotoxicity. Furthermore, LFE increased bone mineralization in zebrafish and prevented bone loss in OVX rat.

CONCLUSION:

Collectively, our findings suggest that LFE exerts its anti-osteoporotic activity through inhibition of osteoclast differentiation and may have potential as a herbal therapeutic or preventive agent for the treatment of osteoporosis.

KEYWORDS:

Bone mineral density; Longan fruit extract; NF-κB; Osteoclast differentiation; RANKL

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