Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation
Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and...
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| description | Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.
Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. Fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐depen |
| doi_str_mv | 10.1002/ptr.8073 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3031132991</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3034662221</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3103-bb9d72df47005de3bee8ab74d2622875c974c40ce2dc8c65df8c64945498af283</originalsourceid><addsrcrecordid>eNp1kd1qFDEUgIModq2CTyABb7yZmr_ZSS5laa1QqJQVvBsyyZk160wyJpnq9KqP4DP6JGZtVRC8yYHw8Z0DH0LPKTmhhLDXU44nkjT8AVpRolRF64Y_RCuialoJKj8eoScp7QkhihHxGB1xWddSCLVCt2dRf4PsPJ4i5Ag6j-Az1sMA105nSNi4NA26ED9uvztvZwMWf3bWw4Kd389xwd2Ctc96F7y7cX6H9ZzD9EnvDt8W6ylMOSSXcBHicXt5taFYm-yuizT4p-hRr4cEz-7nMfpwdrrdnFcXl2_fbd5cVIZTwquuU7ZhthcNIbUF3gFI3TXCsjVjsqmNaoQRxACzRpp1bfvyCiVqoaTumeTH6NWdd4rhywwpt6NLBoZBewhzajnhlHKmFC3oy3_QfZijL9cdKLEuGxn9KzQxpBShb6foRh2XlpL2UKUtVdpDlYK-uBfO3Qj2D_g7QwGqO-CrG2D5r6h9v736JfwJPpWZsg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3034662221</pqid></control><display><type>article</type><title>Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation</title><source>Wiley Journals</source><creator>Yuan, Ziwei ; Yang, Xuejia ; Hu, Zujian ; Gao, Yuanyuan ; Wang, Mengsi ; Xie, Lili ; Zhu, Hengyue ; Chen, Chaosheng ; Lu, Hong ; Bai, Yongheng</creator><creatorcontrib>Yuan, Ziwei ; Yang, Xuejia ; Hu, Zujian ; Gao, Yuanyuan ; Wang, Mengsi ; Xie, Lili ; Zhu, Hengyue ; Chen, Chaosheng ; Lu, Hong ; Bai, Yongheng</creatorcontrib><description>Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.
Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. Fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. These findings indicated that fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.8073</identifier><identifier>PMID: 38558449</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animal tissues ; Apoptosis ; Autophagy ; Binding sites ; Chemotherapy ; Cisplatin ; Electron microscopy ; Epithelial cells ; Epithelium ; fraxetin ; In vivo methods and tests ; Inflammation ; Injury prevention ; Kidneys ; Microscopy ; Molecular docking ; mTORC1 ; Preconditioning ; Pretreatment ; Rapamycin ; renal injury ; siRNA ; Staining ; Transmission electron microscopy</subject><ispartof>Phytotherapy research, 2024-04, Vol.38 (4), p.2077-2093</ispartof><rights>2024 John Wiley & Sons Ltd.</rights><rights>2024 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3103-bb9d72df47005de3bee8ab74d2622875c974c40ce2dc8c65df8c64945498af283</cites><orcidid>0009-0000-8616-2702</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.8073$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.8073$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38558449$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Ziwei</creatorcontrib><creatorcontrib>Yang, Xuejia</creatorcontrib><creatorcontrib>Hu, Zujian</creatorcontrib><creatorcontrib>Gao, Yuanyuan</creatorcontrib><creatorcontrib>Wang, Mengsi</creatorcontrib><creatorcontrib>Xie, Lili</creatorcontrib><creatorcontrib>Zhu, Hengyue</creatorcontrib><creatorcontrib>Chen, Chaosheng</creatorcontrib><creatorcontrib>Lu, Hong</creatorcontrib><creatorcontrib>Bai, Yongheng</creatorcontrib><title>Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.
Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. Fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. These findings indicated that fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.</description><subject>Animal tissues</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Binding sites</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Electron microscopy</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>fraxetin</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Injury prevention</subject><subject>Kidneys</subject><subject>Microscopy</subject><subject>Molecular docking</subject><subject>mTORC1</subject><subject>Preconditioning</subject><subject>Pretreatment</subject><subject>Rapamycin</subject><subject>renal injury</subject><subject>siRNA</subject><subject>Staining</subject><subject>Transmission electron microscopy</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kd1qFDEUgIModq2CTyABb7yZmr_ZSS5laa1QqJQVvBsyyZk160wyJpnq9KqP4DP6JGZtVRC8yYHw8Z0DH0LPKTmhhLDXU44nkjT8AVpRolRF64Y_RCuialoJKj8eoScp7QkhihHxGB1xWddSCLVCt2dRf4PsPJ4i5Ag6j-Az1sMA105nSNi4NA26ED9uvztvZwMWf3bWw4Kd389xwd2Ctc96F7y7cX6H9ZzD9EnvDt8W6ylMOSSXcBHicXt5taFYm-yuizT4p-hRr4cEz-7nMfpwdrrdnFcXl2_fbd5cVIZTwquuU7ZhthcNIbUF3gFI3TXCsjVjsqmNaoQRxACzRpp1bfvyCiVqoaTumeTH6NWdd4rhywwpt6NLBoZBewhzajnhlHKmFC3oy3_QfZijL9cdKLEuGxn9KzQxpBShb6foRh2XlpL2UKUtVdpDlYK-uBfO3Qj2D_g7QwGqO-CrG2D5r6h9v736JfwJPpWZsg</recordid><startdate>202404</startdate><enddate>202404</enddate><creator>Yuan, Ziwei</creator><creator>Yang, Xuejia</creator><creator>Hu, Zujian</creator><creator>Gao, Yuanyuan</creator><creator>Wang, Mengsi</creator><creator>Xie, Lili</creator><creator>Zhu, Hengyue</creator><creator>Chen, Chaosheng</creator><creator>Lu, Hong</creator><creator>Bai, Yongheng</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0000-8616-2702</orcidid></search><sort><creationdate>202404</creationdate><title>Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation</title><author>Yuan, Ziwei ; 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Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.
Cisplatin‐induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti‐inflammatory, and anti‐fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. Fraxetin pretreatment reduced cisplatin‐induced kidney injury in a time‐ and concentration‐dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin‐induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin‐treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT‐repeats binding site on mTORC1 protein. These findings indicated that fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>38558449</pmid><doi>10.1002/ptr.8073</doi><tpages>17</tpages><orcidid>https://orcid.org/0009-0000-8616-2702</orcidid></addata></record> |
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| subjects | Animal tissues Apoptosis Autophagy Binding sites Chemotherapy Cisplatin Electron microscopy Epithelial cells Epithelium fraxetin In vivo methods and tests Inflammation Injury prevention Kidneys Microscopy Molecular docking mTORC1 Preconditioning Pretreatment Rapamycin renal injury siRNA Staining Transmission electron microscopy |
| title | Fraxetin pretreatment alleviates cisplatin‐induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation |
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