{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:58:05Z","timestamp":1760230685985,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI Grants","award":["JP18K14938","JP22K06670"],"award-info":[{"award-number":["JP18K14938","JP22K06670"]}]},{"name":"a grant for novel research project in the School of Pharmacy, Nihon University","award":["JP18K14938","JP22K06670"],"award-info":[{"award-number":["JP18K14938","JP22K06670"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>We screened natural resources for estrogen receptor (ER)-activating and bone metabolism-promoting activities with the aim of finding potential treatments for osteoporosis. A screen of 1531 extracts from Ryukyu Arc plants using a luciferase reporter assay identified an 80% MeOH extract of Scutellaria rubropunctata var. rubropunctata (SRE) with dose-dependent ER transcription-promoting activity. Importantly, SRE had no proliferative effect on human breast cancer cells. SRE enhanced the ALP activity of pre-osteoblast MC3T3-E1 cells after 72 h in culture and slightly enhanced mineralization at 14 and 21 d. SRE did not significantly affect the TRAP activity of RAW264.7 cells. Gene expression analysis in MC3T3-E1 cells by quantitative real-time PCR revealed that SRE upregulated the mRNA levels of Runx2, Osterix (Osx), Osteopontin (Opn), Osteocalcin (Ocn), Smad1, Smad4, and Smad5 at 72 h, and those of Runx2, Osx, Smad1, Smad4, and Smad5 at 21 d of osteogenic induction. Analysis of the expression levels of osteogenic markers suggested that SRE may promote osteogenic differentiation by acting at the early stage of differentiation rather than at the late stage of differentiation. These results indicate that SRE activates ER and induces osteoblast differentiation by activating Runx2 and Osx through the BMP\/Smad pathway, suggesting that SRE may be useful for the prevention and treatment of postmenopausal osteoporosis.<\/jats:p>","DOI":"10.3390\/plants11162075","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T04:20:32Z","timestamp":1660105232000},"page":"2075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of a Whole Plant Extract of Scutellaria rubropunctata var. rubropunctata on Bone Metabolism with Estrogen Receptor Activation"],"prefix":"10.3390","volume":"11","author":[{"given":"Misaki","family":"Watanabe","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacognosy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6373-4613","authenticated-orcid":false,"given":"Tadahiro","family":"Yahagi","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Shirayama","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-8781","authenticated-orcid":false,"given":"Katsunori","family":"Miyake","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Kotani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Shimane University, 1060 Nishikawatsu-cho, Matsue 690-8504, Shimane, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-3079","authenticated-orcid":false,"given":"Takuya","family":"Ogawa","sequence":"additional","affiliation":[{"name":"School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8501, Tochigi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-1981","authenticated-orcid":false,"given":"Keiichi","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1210\/rp.57.1.257","article-title":"Hormonal changes in the menopause transition","volume":"57","author":"Burger","year":"2002","journal-title":"Recent Prog. 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