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Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice

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 Cirsiu...

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Autores principales: Oh, Moon-Sik, Kim, Soo-Il, Sim, Young Eun, Park, Sin-Hye, Kang, Min-Kyung, Kang, Il-Jun, Lim, Soon Sung, Kang, Young-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863805/
https://www.ncbi.nlm.nih.gov/pubmed/36675135
http://dx.doi.org/10.3390/ijms24021620
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author Oh, Moon-Sik
Kim, Soo-Il
Sim, Young Eun
Park, Sin-Hye
Kang, Min-Kyung
Kang, Il-Jun
Lim, Soon Sung
Kang, Young-Hee
author_facet Oh, Moon-Sik
Kim, Soo-Il
Sim, Young Eun
Park, Sin-Hye
Kang, Min-Kyung
Kang, Il-Jun
Lim, Soon Sung
Kang, Young-Hee
author_sort Oh, Moon-Sik
collection PubMed
description 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 17β-estradiol level and enhanced the serum receptor activator of NF-κB 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 αvβ3 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.
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spelling pubmed-98638052023-01-22 Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice Oh, Moon-Sik Kim, Soo-Il Sim, Young Eun Park, Sin-Hye Kang, Min-Kyung Kang, Il-Jun Lim, Soon Sung Kang, Young-Hee Int J Mol Sci Article 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 17β-estradiol level and enhanced the serum receptor activator of NF-κB 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 αvβ3 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. MDPI 2023-01-13 /pmc/articles/PMC9863805/ /pubmed/36675135 http://dx.doi.org/10.3390/ijms24021620 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Moon-Sik
Kim, Soo-Il
Sim, Young Eun
Park, Sin-Hye
Kang, Min-Kyung
Kang, Il-Jun
Lim, Soon Sung
Kang, Young-Hee
Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice
title Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice
title_full Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice
title_fullStr Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice
title_full_unstemmed Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice
title_short Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice
title_sort cirsium setidens water extracts containing linarin block estrogen deprivation-induced bone loss in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863805/
https://www.ncbi.nlm.nih.gov/pubmed/36675135
http://dx.doi.org/10.3390/ijms24021620
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