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

Abstract

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.

Chinese Herbal Medicines for Rheumatoid Arthritis: Text‐Mining the Classical Literature for Potentially Effective Natural Products

“…Extracts [69,70], essential oils [71], shogaols, gingerols [70], 6-gingerol [72] (i) Anti-inflammatory [69][70][71], (ii) Inhibited inflammation-associated osteoclast differentiation [72] Dang gui Angelica sinensis Oliv. Diels Extract [73], ethyl acetate fraction [74], ferulic acid, Z-ligustilide [75], calycosin [76] (i) Anti-inflammatory [75], (ii) Inhibited rheumatoid synovial fibroblast proliferation [74], (iii) Potential interleukin 6R inhibitor [76], (iv) Inhibited osteoclast differentiation [73] Shao yao, Bai shao yao, Chi shao yao…”

Ginger relieves intestinal hypersensitivity of diarrhea predominant irritable bowel syndrome by inhibiting proinflammatory reaction

“…A key step involving in PGE2 production is the conversion of arachidonic acid to prostanoids catalyzed by cyclooxygenase-1 and-2 (COX-1, COX-2) [19]. Previous study have shown that 6-gingerol can inhibit the production of PGE2 and inflammation [20].…”

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca2+ signalling and oxidative stress

“…Achyranthes bidentata polysaccharide, berberine sulphate, nitidine chloride, artesunate and so on were also found to be potential therapeutic candidates for the prevention or treatment of osteoporosis . Other studies also investigated the osteoporotic effects of compounds such as magnolol and polysaccharides …”

“…[20][21][22][23] Other studies also investigated the osteoporotic effects of compounds such as magnolol and polysaccharides. [24][25][26][27][28] As one of BNPs, the compound of Asperpyrone A was isolated from Aspergillus niger with various biological activities including antitumour, antimicrobial and antioxidant. 10,11 Its effects on attenuating RANKL-induced osteoclast formation were identified by our F I G U R E 5 Asperpyrone A suppresses NF-κB signalling pathway.…”