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The Natural Product 6-Gingerol Inhibits Inflammation-Associated Osteoclast Differentiation via Reduction of Prostaglandin E2 Levels

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
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Int. J. Mol. Sci. 2018, 19(7), 2068; https://doi.org/10.3390/ijms19072068
Received: 20 June 2018 / Revised: 11 July 2018 / Accepted: 14 July 2018 / Published: 16 July 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
The natural product 6-gingerol, a major bioactive component of the rhizome of ginger (Zingiber officinale), is known to have several beneficial effects on health, including anti-inflammatory activity. The present study aimed to investigate the effects of 6-gingerol on osteoclast differentiation associated with inflammation. 6-Gingerol inhibited osteoclast differentiation in co-cultures of osteoblasts and osteoclast precursor cells in response to the pro-inflammatory cytokine, interleukin (IL)-1. However, it did not affect osteoclast precursor differentiation into osteoclasts induced by the receptor activator of nuclear factor-κB ligand (RANKL), a key cytokine causing osteoclast differentiation. 6-Gingerol inhibited IL-1-induced RANKL expression in osteoblasts, and the addition of RANKL to the co-cultures overcame 6-gingerol-mediated inhibition of osteoclast differentiation. It also suppressed IL-1-induced prostaglandin E2 (PGE2) production in osteoblasts, and the addition of exogenous PGE2 reversed 6-gingerol-mediated inhibition of IL-induced RANKL expression in osteoblasts and osteoclast differentiation in the co-cultures. We found that 6-gingerol reduced PGE2 levels by suppressing enzymatic activities of cyclooxygenase and PGE synthase, which cooperatively catalyze the conversion of arachidonic acid to PGE2. Our findings demonstrate that 6-gingerol inhibits IL-1-induced osteoclast differentiation via suppression of RANKL expression in osteoblasts though reduction of PGE2 levels, suggesting its potential use in treating inflammatory bone destruction associated with excessive PGE2 production. View Full-Text
Keywords: 6-gingerol; osteoclast; inflammation; interleukin-1; prostaglandin E2 6-gingerol; osteoclast; inflammation; interleukin-1; prostaglandin E2
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Hwang, Y.-H.; Kim, T.; Kim, R.; Ha, H. The Natural Product 6-Gingerol Inhibits Inflammation-Associated Osteoclast Differentiation via Reduction of Prostaglandin E2 Levels. Int. J. Mol. Sci. 2018, 19, 2068.

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