Artemisia annua extract prevents ovariectomy-induced bone loss by blocking receptor activator of nuclear factor kappa-B ligand-induced differentiation of osteoclasts

Sun Kyoung Lee, Hyungkeun Kim, Junhee Park, Hyun Jeong Kim, Ki Rim Kim, Seung Hwa Son, Kwang Kyun Park, Won Yoon Chung

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11 Citations (Scopus)

Abstract

The activities of osteoclasts and osteoblasts are balanced to maintain normal bone density. Many pathological conditions cause osteoclastic bone resorption in excess of osteoblastic bone formation, resulting in osteoporosis. We found that oral administration of Artemisia annua ethanol extract (AaE) or major components, artemisinin and arteannuin B, to ovariectomized (OVX) mice prevented bone loss, as verified by examining three-dimensional images and bone morphometric parameters derived from microcomputed tomography analysis, as well as serum levels of bone turnover markers and proinflammatory cytokines. The administered doses were not toxic to the liver or kidney and showed promising effects that were comparable to those of 17β-estradiol treatment. At non-cytotoxic concentrations, AaE and active components, artemisinin, artemisinic acid, and arteannuin B, potently inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis and the formation of osteoclast-mediated resorption pits. Furthermore, AaE, artemisinin, and arteannuin B remarkably reduced the expression of the c-Fos and NFATc1 transcription factors, which play critical roles in RANKL-induced osteoclast differentiation. Taken together, the in vivo anti-osteoporotic activity of AaE may be derived from the anti-osteoclastic and anti-bone resorptive activities of its active components. AaE has beneficial applications for the prevention and inhibition of osteoporosis and osteoclast-mediated bone diseases.

Original languageEnglish
Article number17332
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

Bibliographical note

Funding Information:
Reagents. A. annua extract (AaE) (MPRBE00725) was provided by the Medicinal Plant Resources Bank (http://knrrb.knrrc.or.kr, Seongnam, Korea), which is supported from the Ministry of Science, ICT, and Future Planning/National Research Foundation of Korea. Artemisinin was obtained from LKT Laboratories (St. Paul, MN), and artemisinic acid and arteannuin B were obtained from ChemFaces (Wuhan, China). Minimum essential medium-alpha (α-MEM), fetal bovine serum (FBS), phosphate-buffered saline (PBS), and antibiotics were purchased from Gibco BRL (Grand Island, NY). Recombinant mouse M-CSF and RANKL were obtained from R&D Systems (Minneapolis, MN). Dimethyl sulfoxide (DMSO), 17β-estradiol (E2), Tween-20, 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT), and Histopaque-1083 were purchased from Sigma-Aldrich (St. Louis, MO). Polyclonal anti-c-Fos and anti-NFATc1 and monoclonal anti-GAPDH antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, CA). All the reagents used in this study were analytical grade.

Funding Information:
This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ011578)” Rural Development Administration, Republic of Korea.

All Science Journal Classification (ASJC) codes

  • General

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