Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model
Background Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendrona...
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| Veröffentlicht in: | Molecular biology reports 2023-04, Vol.50 (4), p.3693-3703 |
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| creator | Mousavi, Sima Vakili, Sina Zal, Fatemeh Savardashtaki, Amir Jafarinia, Morteza Sabetian, Soudabeh Razmjoue, Damoun Veisi, Ali Azadbakht, Omid Sabaghan, Mohamad Behrouj, Hamid |
| description | Background
Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats.
Methods and results
Fifty adult female Sprague–Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone.
Conclusion
Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women. |
| doi_str_mv | 10.1007/s11033-023-08311-w |
| format | Article |
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Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats.
Methods and results
Fifty adult female Sprague–Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone.
Conclusion
Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-023-08311-w</identifier><identifier>PMID: 36829081</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>adults ; Alendronate - pharmacology ; Alendronate - therapeutic use ; Alendronic acid ; Animal Anatomy ; Animal Biochemistry ; animal models ; Animals ; Apoptosis ; Autophagy ; Biomedical and Life Sciences ; Bisphosphonates ; blood serum ; Bone Density ; Bone diseases ; Bone Diseases, Metabolic ; bone fractures ; Bone loss ; bone resorption ; Cancellous bone ; Caspase-3 ; Enzyme-linked immunosorbent assay ; Female ; females ; fluorescent antibody technique ; Histology ; Humans ; Immunofluorescence ; Life Sciences ; Morphology ; Original Article ; osteoblasts ; Osteocalcin ; Osteoclasts ; Osteoporosis ; Osteoporosis - drug therapy ; Osteoporosis - etiology ; Ovariectomy ; Ovariectomy - adverse effects ; Post-menopause ; postmenopause ; quantitative polymerase chain reaction ; Quercetin ; Quercetin - pharmacology ; Rats ; Rats, Sprague-Dawley ; Tibia</subject><ispartof>Molecular biology reports, 2023-04, Vol.50 (4), p.3693-3703</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Nature B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-6e601929bcd86f4a95d5cb9256afb1689fe180bec496e9d593ec57cab04b061c3</citedby><cites>FETCH-LOGICAL-c408t-6e601929bcd86f4a95d5cb9256afb1689fe180bec496e9d593ec57cab04b061c3</cites><orcidid>0000-0001-7587-144X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-023-08311-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-023-08311-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36829081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mousavi, Sima</creatorcontrib><creatorcontrib>Vakili, Sina</creatorcontrib><creatorcontrib>Zal, Fatemeh</creatorcontrib><creatorcontrib>Savardashtaki, Amir</creatorcontrib><creatorcontrib>Jafarinia, Morteza</creatorcontrib><creatorcontrib>Sabetian, Soudabeh</creatorcontrib><creatorcontrib>Razmjoue, Damoun</creatorcontrib><creatorcontrib>Veisi, Ali</creatorcontrib><creatorcontrib>Azadbakht, Omid</creatorcontrib><creatorcontrib>Sabaghan, Mohamad</creatorcontrib><creatorcontrib>Behrouj, Hamid</creatorcontrib><title>Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description>Background
Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats.
Methods and results
Fifty adult female Sprague–Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone.
Conclusion
Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women.</description><subject>adults</subject><subject>Alendronate - pharmacology</subject><subject>Alendronate - therapeutic use</subject><subject>Alendronic acid</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biomedical and Life Sciences</subject><subject>Bisphosphonates</subject><subject>blood serum</subject><subject>Bone Density</subject><subject>Bone diseases</subject><subject>Bone Diseases, Metabolic</subject><subject>bone fractures</subject><subject>Bone loss</subject><subject>bone resorption</subject><subject>Cancellous bone</subject><subject>Caspase-3</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>females</subject><subject>fluorescent antibody technique</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Life Sciences</subject><subject>Morphology</subject><subject>Original Article</subject><subject>osteoblasts</subject><subject>Osteocalcin</subject><subject>Osteoclasts</subject><subject>Osteoporosis</subject><subject>Osteoporosis - drug therapy</subject><subject>Osteoporosis - etiology</subject><subject>Ovariectomy</subject><subject>Ovariectomy - adverse effects</subject><subject>Post-menopause</subject><subject>postmenopause</subject><subject>quantitative polymerase chain reaction</subject><subject>Quercetin</subject><subject>Quercetin - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tibia</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkcuKFTEQhoMoznH0BVxIwI2b1qRz6WQpw3iBARF03aTT1edk6E61SdrhvJDPaWbOqOBCF0Uo8tVfFB8hzzl7zRnr3mTOmRANa2sZwXlz84DsuOpEI21nHpIdE4w30ih-Rp7kfM0Yk7xTj8mZ0Ka1zPAd-fF5g-ShhEhXLBBLcAUyLQegrjYN5gK4YsISPIVpAl8yxYm6GeKYMFa6wgm3_YEuOG6zKwHjHbEVXA9uf6xBI3UrrgVzyHQBf3Ax5CXTuhS_uxRqKC7HJsRx8zDSASPQGXOmyZXbVJifkkeTmzM8u3_Pydd3l18uPjRXn95_vHh71XjJTGk0aMZtawc_Gj1JZ9Wo_GBbpd00cG3sBNywAby0GuyorACvOu8GJgemuRfn5NUpd034bYNc-iVkD_PsIuCW-9ZIa4wW1v4f7UyVxLlUFX35F3qNW4r1kEpZLoWUWleqPVE-1dsTTP2awuLSseesvxXen4T3VXh_J7y_qUMv7qO3YYHx98gvwxUQJyDXr7iH9Gf3P2J_AklWuyM</recordid><startdate>20230401</startdate><enddate>20230401</enddate><creator>Mousavi, Sima</creator><creator>Vakili, Sina</creator><creator>Zal, Fatemeh</creator><creator>Savardashtaki, Amir</creator><creator>Jafarinia, Morteza</creator><creator>Sabetian, Soudabeh</creator><creator>Razmjoue, Damoun</creator><creator>Veisi, Ali</creator><creator>Azadbakht, Omid</creator><creator>Sabaghan, Mohamad</creator><creator>Behrouj, Hamid</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-7587-144X</orcidid></search><sort><creationdate>20230401</creationdate><title>Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model</title><author>Mousavi, Sima ; Vakili, Sina ; Zal, Fatemeh ; Savardashtaki, Amir ; Jafarinia, Morteza ; Sabetian, Soudabeh ; Razmjoue, Damoun ; Veisi, Ali ; Azadbakht, Omid ; Sabaghan, Mohamad ; Behrouj, Hamid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-6e601929bcd86f4a95d5cb9256afb1689fe180bec496e9d593ec57cab04b061c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>adults</topic><topic>Alendronate - pharmacology</topic><topic>Alendronate - therapeutic use</topic><topic>Alendronic acid</topic><topic>Animal Anatomy</topic><topic>Animal Biochemistry</topic><topic>animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biomedical and Life Sciences</topic><topic>Bisphosphonates</topic><topic>blood serum</topic><topic>Bone Density</topic><topic>Bone diseases</topic><topic>Bone Diseases, Metabolic</topic><topic>bone fractures</topic><topic>Bone loss</topic><topic>bone resorption</topic><topic>Cancellous bone</topic><topic>Caspase-3</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>females</topic><topic>fluorescent antibody technique</topic><topic>Histology</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Life Sciences</topic><topic>Morphology</topic><topic>Original Article</topic><topic>osteoblasts</topic><topic>Osteocalcin</topic><topic>Osteoclasts</topic><topic>Osteoporosis</topic><topic>Osteoporosis - drug therapy</topic><topic>Osteoporosis - etiology</topic><topic>Ovariectomy</topic><topic>Ovariectomy - adverse effects</topic><topic>Post-menopause</topic><topic>postmenopause</topic><topic>quantitative polymerase chain reaction</topic><topic>Quercetin</topic><topic>Quercetin - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tibia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mousavi, Sima</creatorcontrib><creatorcontrib>Vakili, Sina</creatorcontrib><creatorcontrib>Zal, Fatemeh</creatorcontrib><creatorcontrib>Savardashtaki, Amir</creatorcontrib><creatorcontrib>Jafarinia, Morteza</creatorcontrib><creatorcontrib>Sabetian, Soudabeh</creatorcontrib><creatorcontrib>Razmjoue, Damoun</creatorcontrib><creatorcontrib>Veisi, Ali</creatorcontrib><creatorcontrib>Azadbakht, Omid</creatorcontrib><creatorcontrib>Sabaghan, Mohamad</creatorcontrib><creatorcontrib>Behrouj, Hamid</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Molecular biology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mousavi, Sima</au><au>Vakili, Sina</au><au>Zal, Fatemeh</au><au>Savardashtaki, Amir</au><au>Jafarinia, Morteza</au><au>Sabetian, Soudabeh</au><au>Razmjoue, Damoun</au><au>Veisi, Ali</au><au>Azadbakht, Omid</au><au>Sabaghan, Mohamad</au><au>Behrouj, Hamid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><addtitle>Mol Biol Rep</addtitle><date>2023-04-01</date><risdate>2023</risdate><volume>50</volume><issue>4</issue><spage>3693</spage><epage>3703</epage><pages>3693-3703</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract>Background
Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats.
Methods and results
Fifty adult female Sprague–Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone.
Conclusion
Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>36829081</pmid><doi>10.1007/s11033-023-08311-w</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7587-144X</orcidid></addata></record> |
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| subjects | adults Alendronate - pharmacology Alendronate - therapeutic use Alendronic acid Animal Anatomy Animal Biochemistry animal models Animals Apoptosis Autophagy Biomedical and Life Sciences Bisphosphonates blood serum Bone Density Bone diseases Bone Diseases, Metabolic bone fractures Bone loss bone resorption Cancellous bone Caspase-3 Enzyme-linked immunosorbent assay Female females fluorescent antibody technique Histology Humans Immunofluorescence Life Sciences Morphology Original Article osteoblasts Osteocalcin Osteoclasts Osteoporosis Osteoporosis - drug therapy Osteoporosis - etiology Ovariectomy Ovariectomy - adverse effects Post-menopause postmenopause quantitative polymerase chain reaction Quercetin Quercetin - pharmacology Rats Rats, Sprague-Dawley Tibia |
| title | Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model |
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