{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:05:21Z","timestamp":1789398321472,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["2021R1A6A1A03044501"],"award-info":[{"award-number":["2021R1A6A1A03044501"]}]},{"name":"Ministry of Education","award":["2022R1A2B5B01001861"],"award-info":[{"award-number":["2022R1A2B5B01001861"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["2021R1A6A1A03044501"],"award-info":[{"award-number":["2021R1A6A1A03044501"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["2022R1A2B5B01001861"],"award-info":[{"award-number":["2022R1A2B5B01001861"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is evident in postmenopausal women and is an osteolytic disease characterized by bone loss that further increases the susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. Edible Cirsium setidens contains various polyphenols of linarin, pectolinarin, and apigenin with antioxidant and hepatoprotective effects. This study aimed to determine whether Cirsium setidens water extracts (CSEs), the component linarin, and its aglycone acacetin blocked ovariectomy (OVX)-induced bone loss. This study employed OVX C57BL\/6 female mice as a model for postmenopausal osteoporosis. CSEs, acacetin, or linarin was orally administrated to OVX mice at a dose of 20 mg\/kg for 8 weeks. Surgical estrogen loss in mice for 8 weeks reduced bone mineral density (BMD) of mouse femur and serum 17\u03b2-estradiol level and enhanced the serum receptor activator of NF-\u03baB ligand\/osteoprotegerin ratio with uterine atrophy. CSEs and linarin reversed such adverse effects and enhanced femoral BMD in OVX mice. Oral administration of CSEs and linarin attenuated tartrate-resistant acid phosphate activity and the induction of \u03b1v\u03b23 integrins and proton suppliers in resorption lacunae in femoral bone tissue of OVX mice. In addition, CSEs and linarin curtailed the bone levels of cathepsin K and matrix metalloproteinase-9 responsible for osteoclastic bone resorption. On the other hand, CSEs and linarin enhanced the formation of trabecular bones in estrogen-deficient femur with increased induction of osteocalcin and osteopontin. Further, treatment with CSEs and linarin enhanced the collagen formation-responsive propeptide levels in the circulation along with the increase in the tissue non-specific alkaline phosphatase level in bone exposed to OVX. Supplementing CSEs, acacetin, or linarin to OVX mice elevated the formation of collagen fibers in OVX trabecular bone, evidenced using Picrosirius red staining. Accordingly, CSEs and linarin were effective in retarding osteoclastic bone resorption and promoting osteoblastic bone matrix mineralization under OVX conditions. Therefore, linarin, which is abundant in CSEs, may be a natural compound for targeting postmenopausal osteoporosis and pathological osteoresorptive disorders.<\/jats:p>","DOI":"10.3390\/ijms24021620","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:04:45Z","timestamp":1673834685000},"page":"1620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Moon-Sik","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Il","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Eun","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1656-185X","authenticated-orcid":false,"given":"Sin-Hye","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Kyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Andong National University, Andong 36729, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0314-5195","authenticated-orcid":false,"given":"Il-Jun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4548-1285","authenticated-orcid":false,"given":"Soon Sung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2039-7968","authenticated-orcid":false,"given":"Young-Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00003086-200003000-00016","article-title":"Osteoporosis","volume":"372","author":"Lane","year":"2000","journal-title":"Clin. 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