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Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries
Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthca...
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Published in: | Antioxidants 2023-12, Vol.12 (12), p.2119 |
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description | Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases. |
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Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases.</description><identifier>ISSN: 2076-3921</identifier><identifier>EISSN: 2076-3921</identifier><identifier>DOI: 10.3390/antiox12122119</identifier><identifier>PMID: 38136238</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antioxidants ; Cells ; Drugs ; Ferroptosis ; Flow cytometry ; Glutathione peroxidase ; glutathione peroxidase 4 ; Injuries ; Ischemia ; Kidneys ; Lipid peroxidation ; Lipids ; Liver ; Liver diseases ; Medical research ; Medicine, Experimental ; Neurodegeneration ; renal ischemia reperfusion ; Reperfusion ; Silibinin ; Silymarin</subject><ispartof>Antioxidants, 2023-12, Vol.12 (12), p.2119</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-2f2c9f6bef3fcea624f588ed5c5fdffd4d660cd71b6c29f619acd8261ce86ee63</citedby><cites>FETCH-LOGICAL-c496t-2f2c9f6bef3fcea624f588ed5c5fdffd4d660cd71b6c29f619acd8261ce86ee63</cites><orcidid>0000-0003-2889-4491</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2904634585/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2904634585?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25753,27924,27925,37012,37013,44590,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38136238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duan, Wentao</creatorcontrib><creatorcontrib>Ou, Zexian</creatorcontrib><creatorcontrib>Huang, Yuxing</creatorcontrib><creatorcontrib>Zhang, Yifan</creatorcontrib><creatorcontrib>Zhang, Lan</creatorcontrib><creatorcontrib>Zhao, Yanan</creatorcontrib><creatorcontrib>He, Ruikun</creatorcontrib><creatorcontrib>Zhang, Yihan</creatorcontrib><creatorcontrib>Ge, Yuanlong</creatorcontrib><creatorcontrib>Lou, Huiling</creatorcontrib><creatorcontrib>Ju, Zhenyu</creatorcontrib><creatorcontrib>Hu, Qian</creatorcontrib><title>Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries</title><title>Antioxidants</title><addtitle>Antioxidants (Basel)</addtitle><description>Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases.</description><subject>Antioxidants</subject><subject>Cells</subject><subject>Drugs</subject><subject>Ferroptosis</subject><subject>Flow cytometry</subject><subject>Glutathione peroxidase</subject><subject>glutathione peroxidase 4</subject><subject>Injuries</subject><subject>Ischemia</subject><subject>Kidneys</subject><subject>Lipid peroxidation</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Neurodegeneration</subject><subject>renal ischemia reperfusion</subject><subject>Reperfusion</subject><subject>Silibinin</subject><subject>Silymarin</subject><issn>2076-3921</issn><issn>2076-3921</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkstvFSEUxomxsU3t1qWZxI2bqcNzYNncWHtjExPbrgmPQ-VmLlxhJtH_Xm5fVlNYcDj5fR8cOAi9w8MppWr4ZNIc8y9MMCEYq1foiAyj6Kki-PWz-BCd1LoZ2lCYykG9QYdUYioIlUfo61Wcoo0ppm6dfrRort0Kpqk7h1Lybs411s4k_3zff4fJzOC761jrAk24WUqE-hYdBDNVOHlYj9HN-efr1UV_-e3LenV22TumxNyTQJwKwkKgwYERhAUuJXjuePAheOaFGJwfsRWONBAr47wkAjuQAkDQY7S-9_XZbPSuxK0pv3U2Ud8lcrnVpszRTaA5sZK1SqnzmFlgimEpcPNhlkhrx-b18d5rV_LPBeqst7G69gAmQV6qJmrgHKuRyYZ--A_d5KWkVumeYoIyLvlf6ta082MKeS7G7U312TiOTHE-0kadvkC16WEbXU4QYsu_JHAl11ogPNWNB71vBv1vMzTB-4fbLnYL_gl__Hr6B8iXrrE</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Duan, Wentao</creator><creator>Ou, Zexian</creator><creator>Huang, Yuxing</creator><creator>Zhang, Yifan</creator><creator>Zhang, Lan</creator><creator>Zhao, Yanan</creator><creator>He, Ruikun</creator><creator>Zhang, Yihan</creator><creator>Ge, Yuanlong</creator><creator>Lou, Huiling</creator><creator>Ju, Zhenyu</creator><creator>Hu, Qian</creator><general>MDPI AG</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2889-4491</orcidid></search><sort><creationdate>20231201</creationdate><title>Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries</title><author>Duan, Wentao ; 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Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38136238</pmid><doi>10.3390/antiox12122119</doi><orcidid>https://orcid.org/0000-0003-2889-4491</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antioxidants Cells Drugs Ferroptosis Flow cytometry Glutathione peroxidase glutathione peroxidase 4 Injuries Ischemia Kidneys Lipid peroxidation Lipids Liver Liver diseases Medical research Medicine, Experimental Neurodegeneration renal ischemia reperfusion Reperfusion Silibinin Silymarin |
title | Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries |
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