Lithospermic acid improves liver fibrosis through Piezo1-mediated oxidative stress and inflammation
•Lithospermic acid (LA) improved carbon tetrachloride (CCl4) induced liver fibrosis.•LA significantly decreased Piezo1 expression and inhibited macrophage Piezo1 activation.•LA suppressed Piezo1/Ca2+-mediated oxidative stress and Piezo1/Notch-mediated inflammation. Hepatic fibrosis is becoming an in...
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| Veröffentlicht in: | Phytomedicine (Stuttgart) 2024-11, Vol.134, p.155974, Article 155974 |
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| creator | Luo, Shangfei Yang, Bo Xu, Honglin Pan, Xianmei Chen, Xin Jue, Xiaoyu Liu, Silin Wan, Rentao Tan, Qiaorui Yao, Youfen Chen, Xiaoting Jiang, Jintao Deng, Bo Li, Jing |
| description | •Lithospermic acid (LA) improved carbon tetrachloride (CCl4) induced liver fibrosis.•LA significantly decreased Piezo1 expression and inhibited macrophage Piezo1 activation.•LA suppressed Piezo1/Ca2+-mediated oxidative stress and Piezo1/Notch-mediated inflammation.
Hepatic fibrosis is becoming an increasingly serious public health issue worldwide. Although liver transplantation is the only and definitive treatment for end-stage liver fibrosis, traditional Chinese medicine offers certain benefits in the treatment of advanced hepatic fibrosis.
This study aims to explore the protective effect of lithospermic acid (LA), an extraction from Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, known as Danshen in Chinese), on liver fibrosis and investigate its potential mechanisms.
Mice were treated with carbon tetrachloride (CCl4) via intraperitoneal injection for 4 weeks. LA was orally administered or colchicine (COL) was injected intraperitoneally for 3 weeks starting one week after the initial CCl4 injection. After the LA treatment, we observed a decrease in the fibrosis index and an improvement in liver function. Molecular docking results revealed that Piezo1 may be a potential pharmacological target of LA. The further experimental results showed that LA inhibited Piezo1 activation and expression in macrophages. Mechanistically, both Piezo1/Notch-mediated inflammation and oxidative stress regulated by the Piezo1/Ca2+ pathway were alleviated in fibrotic livers following LA treatment. Moreover, less oxidative stress and Notch activation were observed in the deficiency of macrophage Piezo1 (Piezo1ΔLysM) mice. In addition, Piezo1ΔLysM partially counteracted the pharmacological effects of LA on liver fibrosis.
In conclusion, our present study corroborated LA limits the progression of liver fibrosis by regulating Piezo1-mediated oxidative stress and inflammation. These results indicate that LA could be a potential medication for hepatic fibrosis treatment.
[Display omitted] |
| doi_str_mv | 10.1016/j.phymed.2024.155974 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3099855827</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0944711324006329</els_id><sourcerecordid>3099855827</sourcerecordid><originalsourceid>FETCH-LOGICAL-c241t-80d2914e2552b5abae4e47bcc1a20457af8cdc47bcc7ed80e90eed9b2038ba663</originalsourceid><addsrcrecordid>eNp9kMFOGzEQhq2qqIS0b1AhH3vZYHvt9fqChKK2IEWCA0jcLK892zjaXQd7E5E-PQ5Lrpwsjb-Zf-ZD6CclC0podbVZbNeHHtyCEcYXVAgl-Rc0oxWtC6LE81c0I4rzQlJanqOLlDaEUK4k-YbOS8WorIScIbvy4zqkLcTeW2ysd9j32xj2kHDn9xBx65sYkk94XMew-7fGDx7-B1rkaG9GcDi8emfGzOI0RkgJmyEPGdrO9H2uh-E7OmtNl-DHxztHT39-Py5vi9X937vlzaqwjNOxqIljinJgQrBGmMYABy4ba6lhhAtp2to6-16R4GoCigA41TBS1o2pqnKOfk1z8_4vO0ij7n2y0HVmgLBLuiRK1ULUTGaUT6jNt6UIrd5G35t40JToo1690ZNefdSrJ7257fIjYdcc_05NJ58ZuJ4AyHfuPUSdrIfBZlcR7Khd8J8nvAHTa5Bg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3099855827</pqid></control><display><type>article</type><title>Lithospermic acid improves liver fibrosis through Piezo1-mediated oxidative stress and inflammation</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Luo, Shangfei ; Yang, Bo ; Xu, Honglin ; Pan, Xianmei ; Chen, Xin ; Jue, Xiaoyu ; Liu, Silin ; Wan, Rentao ; Tan, Qiaorui ; Yao, Youfen ; Chen, Xiaoting ; Jiang, Jintao ; Deng, Bo ; Li, Jing</creator><creatorcontrib>Luo, Shangfei ; Yang, Bo ; Xu, Honglin ; Pan, Xianmei ; Chen, Xin ; Jue, Xiaoyu ; Liu, Silin ; Wan, Rentao ; Tan, Qiaorui ; Yao, Youfen ; Chen, Xiaoting ; Jiang, Jintao ; Deng, Bo ; Li, Jing</creatorcontrib><description>•Lithospermic acid (LA) improved carbon tetrachloride (CCl4) induced liver fibrosis.•LA significantly decreased Piezo1 expression and inhibited macrophage Piezo1 activation.•LA suppressed Piezo1/Ca2+-mediated oxidative stress and Piezo1/Notch-mediated inflammation.
Hepatic fibrosis is becoming an increasingly serious public health issue worldwide. Although liver transplantation is the only and definitive treatment for end-stage liver fibrosis, traditional Chinese medicine offers certain benefits in the treatment of advanced hepatic fibrosis.
This study aims to explore the protective effect of lithospermic acid (LA), an extraction from Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, known as Danshen in Chinese), on liver fibrosis and investigate its potential mechanisms.
Mice were treated with carbon tetrachloride (CCl4) via intraperitoneal injection for 4 weeks. LA was orally administered or colchicine (COL) was injected intraperitoneally for 3 weeks starting one week after the initial CCl4 injection. After the LA treatment, we observed a decrease in the fibrosis index and an improvement in liver function. Molecular docking results revealed that Piezo1 may be a potential pharmacological target of LA. The further experimental results showed that LA inhibited Piezo1 activation and expression in macrophages. Mechanistically, both Piezo1/Notch-mediated inflammation and oxidative stress regulated by the Piezo1/Ca2+ pathway were alleviated in fibrotic livers following LA treatment. Moreover, less oxidative stress and Notch activation were observed in the deficiency of macrophage Piezo1 (Piezo1ΔLysM) mice. In addition, Piezo1ΔLysM partially counteracted the pharmacological effects of LA on liver fibrosis.
In conclusion, our present study corroborated LA limits the progression of liver fibrosis by regulating Piezo1-mediated oxidative stress and inflammation. These results indicate that LA could be a potential medication for hepatic fibrosis treatment.
[Display omitted]</description><identifier>ISSN: 0944-7113</identifier><identifier>ISSN: 1618-095X</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2024.155974</identifier><identifier>PMID: 39217657</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Animals ; Benzofurans - pharmacology ; Carbon Tetrachloride ; Depsides - pharmacology ; Drugs, Chinese Herbal - pharmacology ; Inflammation ; Inflammation - drug therapy ; Ion Channels - metabolism ; Lithospermic acid ; Liver - drug effects ; Liver - pathology ; Liver Cirrhosis - drug therapy ; Liver fibrosis ; Macrophages ; Macrophages - drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Oxidative stress ; Oxidative Stress - drug effects ; Piezo1 ; RAW 264.7 Cells ; Receptors, Notch - metabolism ; Salvia miltiorrhiza - chemistry</subject><ispartof>Phytomedicine (Stuttgart), 2024-11, Vol.134, p.155974, Article 155974</ispartof><rights>2024 Elsevier GmbH</rights><rights>Copyright © 2024 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c241t-80d2914e2552b5abae4e47bcc1a20457af8cdc47bcc7ed80e90eed9b2038ba663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.phymed.2024.155974$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39217657$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Shangfei</creatorcontrib><creatorcontrib>Yang, Bo</creatorcontrib><creatorcontrib>Xu, Honglin</creatorcontrib><creatorcontrib>Pan, Xianmei</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Jue, Xiaoyu</creatorcontrib><creatorcontrib>Liu, Silin</creatorcontrib><creatorcontrib>Wan, Rentao</creatorcontrib><creatorcontrib>Tan, Qiaorui</creatorcontrib><creatorcontrib>Yao, Youfen</creatorcontrib><creatorcontrib>Chen, Xiaoting</creatorcontrib><creatorcontrib>Jiang, Jintao</creatorcontrib><creatorcontrib>Deng, Bo</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><title>Lithospermic acid improves liver fibrosis through Piezo1-mediated oxidative stress and inflammation</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>•Lithospermic acid (LA) improved carbon tetrachloride (CCl4) induced liver fibrosis.•LA significantly decreased Piezo1 expression and inhibited macrophage Piezo1 activation.•LA suppressed Piezo1/Ca2+-mediated oxidative stress and Piezo1/Notch-mediated inflammation.
Hepatic fibrosis is becoming an increasingly serious public health issue worldwide. Although liver transplantation is the only and definitive treatment for end-stage liver fibrosis, traditional Chinese medicine offers certain benefits in the treatment of advanced hepatic fibrosis.
This study aims to explore the protective effect of lithospermic acid (LA), an extraction from Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, known as Danshen in Chinese), on liver fibrosis and investigate its potential mechanisms.
Mice were treated with carbon tetrachloride (CCl4) via intraperitoneal injection for 4 weeks. LA was orally administered or colchicine (COL) was injected intraperitoneally for 3 weeks starting one week after the initial CCl4 injection. After the LA treatment, we observed a decrease in the fibrosis index and an improvement in liver function. Molecular docking results revealed that Piezo1 may be a potential pharmacological target of LA. The further experimental results showed that LA inhibited Piezo1 activation and expression in macrophages. Mechanistically, both Piezo1/Notch-mediated inflammation and oxidative stress regulated by the Piezo1/Ca2+ pathway were alleviated in fibrotic livers following LA treatment. Moreover, less oxidative stress and Notch activation were observed in the deficiency of macrophage Piezo1 (Piezo1ΔLysM) mice. In addition, Piezo1ΔLysM partially counteracted the pharmacological effects of LA on liver fibrosis.
In conclusion, our present study corroborated LA limits the progression of liver fibrosis by regulating Piezo1-mediated oxidative stress and inflammation. These results indicate that LA could be a potential medication for hepatic fibrosis treatment.
[Display omitted]</description><subject>Animals</subject><subject>Benzofurans - pharmacology</subject><subject>Carbon Tetrachloride</subject><subject>Depsides - pharmacology</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Ion Channels - metabolism</subject><subject>Lithospermic acid</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis - drug therapy</subject><subject>Liver fibrosis</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Docking Simulation</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Piezo1</subject><subject>RAW 264.7 Cells</subject><subject>Receptors, Notch - metabolism</subject><subject>Salvia miltiorrhiza - chemistry</subject><issn>0944-7113</issn><issn>1618-095X</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFOGzEQhq2qqIS0b1AhH3vZYHvt9fqChKK2IEWCA0jcLK892zjaXQd7E5E-PQ5Lrpwsjb-Zf-ZD6CclC0podbVZbNeHHtyCEcYXVAgl-Rc0oxWtC6LE81c0I4rzQlJanqOLlDaEUK4k-YbOS8WorIScIbvy4zqkLcTeW2ysd9j32xj2kHDn9xBx65sYkk94XMew-7fGDx7-B1rkaG9GcDi8emfGzOI0RkgJmyEPGdrO9H2uh-E7OmtNl-DHxztHT39-Py5vi9X937vlzaqwjNOxqIljinJgQrBGmMYABy4ba6lhhAtp2to6-16R4GoCigA41TBS1o2pqnKOfk1z8_4vO0ij7n2y0HVmgLBLuiRK1ULUTGaUT6jNt6UIrd5G35t40JToo1690ZNefdSrJ7257fIjYdcc_05NJ58ZuJ4AyHfuPUSdrIfBZlcR7Khd8J8nvAHTa5Bg</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Luo, Shangfei</creator><creator>Yang, Bo</creator><creator>Xu, Honglin</creator><creator>Pan, Xianmei</creator><creator>Chen, Xin</creator><creator>Jue, Xiaoyu</creator><creator>Liu, Silin</creator><creator>Wan, Rentao</creator><creator>Tan, Qiaorui</creator><creator>Yao, Youfen</creator><creator>Chen, Xiaoting</creator><creator>Jiang, Jintao</creator><creator>Deng, Bo</creator><creator>Li, Jing</creator><general>Elsevier GmbH</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>7X8</scope></search><sort><creationdate>202411</creationdate><title>Lithospermic acid improves liver fibrosis through Piezo1-mediated oxidative stress and inflammation</title><author>Luo, Shangfei ; Yang, Bo ; Xu, Honglin ; Pan, Xianmei ; Chen, Xin ; Jue, Xiaoyu ; Liu, Silin ; Wan, Rentao ; Tan, Qiaorui ; Yao, Youfen ; Chen, Xiaoting ; Jiang, Jintao ; Deng, Bo ; Li, Jing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c241t-80d2914e2552b5abae4e47bcc1a20457af8cdc47bcc7ed80e90eed9b2038ba663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Benzofurans - pharmacology</topic><topic>Carbon Tetrachloride</topic><topic>Depsides - pharmacology</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Ion Channels - metabolism</topic><topic>Lithospermic acid</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis - drug therapy</topic><topic>Liver fibrosis</topic><topic>Macrophages</topic><topic>Macrophages - drug effects</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Docking Simulation</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Piezo1</topic><topic>RAW 264.7 Cells</topic><topic>Receptors, Notch - metabolism</topic><topic>Salvia miltiorrhiza - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Shangfei</creatorcontrib><creatorcontrib>Yang, Bo</creatorcontrib><creatorcontrib>Xu, Honglin</creatorcontrib><creatorcontrib>Pan, Xianmei</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Jue, Xiaoyu</creatorcontrib><creatorcontrib>Liu, Silin</creatorcontrib><creatorcontrib>Wan, Rentao</creatorcontrib><creatorcontrib>Tan, Qiaorui</creatorcontrib><creatorcontrib>Yao, Youfen</creatorcontrib><creatorcontrib>Chen, Xiaoting</creatorcontrib><creatorcontrib>Jiang, Jintao</creatorcontrib><creatorcontrib>Deng, Bo</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Shangfei</au><au>Yang, Bo</au><au>Xu, Honglin</au><au>Pan, Xianmei</au><au>Chen, Xin</au><au>Jue, Xiaoyu</au><au>Liu, Silin</au><au>Wan, Rentao</au><au>Tan, Qiaorui</au><au>Yao, Youfen</au><au>Chen, Xiaoting</au><au>Jiang, Jintao</au><au>Deng, Bo</au><au>Li, Jing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lithospermic acid improves liver fibrosis through Piezo1-mediated oxidative stress and inflammation</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2024-11</date><risdate>2024</risdate><volume>134</volume><spage>155974</spage><pages>155974-</pages><artnum>155974</artnum><issn>0944-7113</issn><issn>1618-095X</issn><eissn>1618-095X</eissn><abstract>•Lithospermic acid (LA) improved carbon tetrachloride (CCl4) induced liver fibrosis.•LA significantly decreased Piezo1 expression and inhibited macrophage Piezo1 activation.•LA suppressed Piezo1/Ca2+-mediated oxidative stress and Piezo1/Notch-mediated inflammation.
Hepatic fibrosis is becoming an increasingly serious public health issue worldwide. Although liver transplantation is the only and definitive treatment for end-stage liver fibrosis, traditional Chinese medicine offers certain benefits in the treatment of advanced hepatic fibrosis.
This study aims to explore the protective effect of lithospermic acid (LA), an extraction from Salvia miltiorrhiza (the roots of S. miltiorrhiza Bunge, known as Danshen in Chinese), on liver fibrosis and investigate its potential mechanisms.
Mice were treated with carbon tetrachloride (CCl4) via intraperitoneal injection for 4 weeks. LA was orally administered or colchicine (COL) was injected intraperitoneally for 3 weeks starting one week after the initial CCl4 injection. After the LA treatment, we observed a decrease in the fibrosis index and an improvement in liver function. Molecular docking results revealed that Piezo1 may be a potential pharmacological target of LA. The further experimental results showed that LA inhibited Piezo1 activation and expression in macrophages. Mechanistically, both Piezo1/Notch-mediated inflammation and oxidative stress regulated by the Piezo1/Ca2+ pathway were alleviated in fibrotic livers following LA treatment. Moreover, less oxidative stress and Notch activation were observed in the deficiency of macrophage Piezo1 (Piezo1ΔLysM) mice. In addition, Piezo1ΔLysM partially counteracted the pharmacological effects of LA on liver fibrosis.
In conclusion, our present study corroborated LA limits the progression of liver fibrosis by regulating Piezo1-mediated oxidative stress and inflammation. These results indicate that LA could be a potential medication for hepatic fibrosis treatment.
[Display omitted]</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>39217657</pmid><doi>10.1016/j.phymed.2024.155974</doi></addata></record> |
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| subjects | Animals Benzofurans - pharmacology Carbon Tetrachloride Depsides - pharmacology Drugs, Chinese Herbal - pharmacology Inflammation Inflammation - drug therapy Ion Channels - metabolism Lithospermic acid Liver - drug effects Liver - pathology Liver Cirrhosis - drug therapy Liver fibrosis Macrophages Macrophages - drug effects Male Mice Mice, Inbred C57BL Molecular Docking Simulation Oxidative stress Oxidative Stress - drug effects Piezo1 RAW 264.7 Cells Receptors, Notch - metabolism Salvia miltiorrhiza - chemistry |
| title | Lithospermic acid improves liver fibrosis through Piezo1-mediated oxidative stress and inflammation |
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