{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:59:04Z","timestamp":1778587144632,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A5A2027340"],"award-info":[{"award-number":["2019R1A5A2027340"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-\u03b2-d-apiofuranosyl-(1\u21926)-\u03b2-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin \u03b23 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-\u03ba\u03b2 translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.<\/jats:p>","DOI":"10.3390\/ijms22010222","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T10:33:56Z","timestamp":1609151636000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibitory Effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-\u03b2-d-apiofuranosyl-(1\u21926)-\u03b2-d-glucopyranoside on RANKL-Induced Osteoclast Differentiation and ROS Generation in Macrophages"],"prefix":"10.3390","volume":"22","author":[{"given":"Eun-Nam","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy, Keimyung University, Daegu 42601, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga-Ram","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Keimyung University, Daegu 42601, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Sik","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5285-9138","authenticated-orcid":false,"given":"Ki Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gil-Saeng","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Keimyung University, Daegu 42601, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.bone.2006.09.023","article-title":"The molecular understanding of osteoclast differentiation","volume":"40","author":"Asagiri","year":"2007","journal-title":"Bone"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ajog.2005.08.047","article-title":"Epidemiology, Etiology, and Diagnosis of Osteoporosis","volume":"194","author":"Lane","year":"2006","journal-title":"Am. 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