The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury
Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to...
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| creator | Song, Chunhui Williams, Kevin Liu, Changhui Xu, Qin Chang, Yongsheng Gao, Yong Gao, Weihang Yang, Zehong Cheng, Bo Zhang, Yuan Yang, Xingping Wei, Li Zhang, Jiecheng Gao, Zhao Miao, Wei |
| description | Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose. |
| doi_str_mv | 10.1155/2020/8026838 |
| format | Article |
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Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2020/8026838</identifier><identifier>PMID: 32454943</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Acetaminophen ; Acetaminophen - adverse effects ; Acids ; Acute Disease ; Analgesics ; Animal experimentation ; Animals ; Antioxidants - metabolism ; Bile ; Cytokines ; Cytokines - metabolism ; Drug dosages ; Drug Overdose - drug therapy ; Drug Overdose - genetics ; Drug Overdose - pathology ; Drugs ; Experiments ; Furocoumarins - chemistry ; Furocoumarins - pharmacology ; Furocoumarins - therapeutic use ; Gene amplification ; Gene Expression Regulation - drug effects ; Health aspects ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Hepatocytes - pathology ; Inflammation ; Inflammation Mediators - metabolism ; Laboratories ; Lipopolysaccharides ; Liver ; Liver - injuries ; Liver - pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria - drug effects ; Mitochondria - metabolism ; Models, Biological ; Overdose ; Oxidative stress ; Oxidative Stress - drug effects ; Protective Agents - pharmacology ; Protective Agents - therapeutic use ; Proteins ; Receptors, Cytoplasmic and Nuclear - deficiency ; Receptors, Cytoplasmic and Nuclear - metabolism ; Signal Transduction - drug effects ; Sirtuin 1 - metabolism ; Transcriptome - genetics ; Up-Regulation</subject><ispartof>Oxidative medicine and cellular longevity, 2020, Vol.2020 (2020), p.1-17</ispartof><rights>Copyright © 2020 Zhao Gao et al.</rights><rights>COPYRIGHT 2020 John Wiley & Sons, Inc.</rights><rights>Copyright © 2020 Zhao Gao et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Zhao Gao et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-ecf234b679313d0c422cb8d4663876dc0976e88891403cd1ff8db9ab78863e613</citedby><cites>FETCH-LOGICAL-c499t-ecf234b679313d0c422cb8d4663876dc0976e88891403cd1ff8db9ab78863e613</cites><orcidid>0000-0002-7795-3649 ; 0000-0002-2146-7342 ; 0000-0001-6165-4313 ; 0000-0002-7846-8127</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243017/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243017/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32454943$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>García-Rivas, Gerardo</contributor><creatorcontrib>Song, Chunhui</creatorcontrib><creatorcontrib>Williams, Kevin</creatorcontrib><creatorcontrib>Liu, Changhui</creatorcontrib><creatorcontrib>Xu, Qin</creatorcontrib><creatorcontrib>Chang, Yongsheng</creatorcontrib><creatorcontrib>Gao, Yong</creatorcontrib><creatorcontrib>Gao, Weihang</creatorcontrib><creatorcontrib>Yang, Zehong</creatorcontrib><creatorcontrib>Cheng, Bo</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Yang, Xingping</creatorcontrib><creatorcontrib>Wei, Li</creatorcontrib><creatorcontrib>Zhang, Jiecheng</creatorcontrib><creatorcontrib>Gao, Zhao</creatorcontrib><creatorcontrib>Miao, Wei</creatorcontrib><title>The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><description>Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.</description><subject>Acetaminophen</subject><subject>Acetaminophen - adverse effects</subject><subject>Acids</subject><subject>Acute Disease</subject><subject>Analgesics</subject><subject>Animal experimentation</subject><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>Bile</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Drug dosages</subject><subject>Drug Overdose - drug therapy</subject><subject>Drug Overdose - genetics</subject><subject>Drug Overdose - pathology</subject><subject>Drugs</subject><subject>Experiments</subject><subject>Furocoumarins - chemistry</subject><subject>Furocoumarins - pharmacology</subject><subject>Furocoumarins - therapeutic use</subject><subject>Gene amplification</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Health aspects</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Hepatocytes - pathology</subject><subject>Inflammation</subject><subject>Inflammation Mediators - metabolism</subject><subject>Laboratories</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>Liver - injuries</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Models, Biological</subject><subject>Overdose</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Protective Agents - pharmacology</subject><subject>Protective Agents - therapeutic use</subject><subject>Proteins</subject><subject>Receptors, Cytoplasmic and Nuclear - deficiency</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Sirtuin 1 - metabolism</subject><subject>Transcriptome - genetics</subject><subject>Up-Regulation</subject><issn>1942-0900</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkc9rFDEYhoMotlZvniXgUcfm12SSi7CUqgsL9VAvXkIm-dLNspOsmZmV_vem7rrVm6fvhe_h4YUXodeUfKC0bS8ZYeRSESYVV0_QOdWCNURr8fSUCTlDL8ZxQ4jkTNDn6KyeVmjBz9H32zXgryVP4Ka4B3wdQk0jzgEvhx0UO-USE84JLxxMdogp79aQ8M0eis8jNMvkZwe-vucJ8Ko6Cl6mzVzuX6JnwW5HeHW8F-jbp-vbqy_N6ubz8mqxapzQemrABcZFLzvNKffECcZcr7yQkqtOekd0J0Eppakg3HkagvK9tn2nlOQgKb9AHw_e3dwP4B2kqdit2ZU42HJvso3m30-Ka3OX96ZjghPaVcHbo6DkHzOMk9nkuaTa2TBBJOuobvUjdWe3YGIKucrcEEdnFpIp2nXsd5n3B8qVPI4FwqkHJeZhL_OwlznuVfE3f3c_wX8GqsC7A7COyduf8T91UBkI9pFmpG0J4b8A956mJw</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Song, Chunhui</creator><creator>Williams, Kevin</creator><creator>Liu, Changhui</creator><creator>Xu, Qin</creator><creator>Chang, Yongsheng</creator><creator>Gao, Yong</creator><creator>Gao, Weihang</creator><creator>Yang, Zehong</creator><creator>Cheng, Bo</creator><creator>Zhang, Yuan</creator><creator>Yang, Xingping</creator><creator>Wei, Li</creator><creator>Zhang, Jiecheng</creator><creator>Gao, Zhao</creator><creator>Miao, Wei</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7795-3649</orcidid><orcidid>https://orcid.org/0000-0002-2146-7342</orcidid><orcidid>https://orcid.org/0000-0001-6165-4313</orcidid><orcidid>https://orcid.org/0000-0002-7846-8127</orcidid></search><sort><creationdate>2020</creationdate><title>The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury</title><author>Song, Chunhui ; Williams, Kevin ; Liu, Changhui ; Xu, Qin ; Chang, Yongsheng ; Gao, Yong ; Gao, Weihang ; Yang, Zehong ; Cheng, Bo ; Zhang, Yuan ; Yang, Xingping ; Wei, Li ; Zhang, Jiecheng ; Gao, Zhao ; Miao, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-ecf234b679313d0c422cb8d4663876dc0976e88891403cd1ff8db9ab78863e613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acetaminophen</topic><topic>Acetaminophen - 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Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>32454943</pmid><doi>10.1155/2020/8026838</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-7795-3649</orcidid><orcidid>https://orcid.org/0000-0002-2146-7342</orcidid><orcidid>https://orcid.org/0000-0001-6165-4313</orcidid><orcidid>https://orcid.org/0000-0002-7846-8127</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Open Access; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; PubMed Central Open Access |
| subjects | Acetaminophen Acetaminophen - adverse effects Acids Acute Disease Analgesics Animal experimentation Animals Antioxidants - metabolism Bile Cytokines Cytokines - metabolism Drug dosages Drug Overdose - drug therapy Drug Overdose - genetics Drug Overdose - pathology Drugs Experiments Furocoumarins - chemistry Furocoumarins - pharmacology Furocoumarins - therapeutic use Gene amplification Gene Expression Regulation - drug effects Health aspects Hepatocytes - drug effects Hepatocytes - metabolism Hepatocytes - pathology Inflammation Inflammation Mediators - metabolism Laboratories Lipopolysaccharides Liver Liver - injuries Liver - pathology Male Mice, Inbred C57BL Mice, Knockout Mitochondria - drug effects Mitochondria - metabolism Models, Biological Overdose Oxidative stress Oxidative Stress - drug effects Protective Agents - pharmacology Protective Agents - therapeutic use Proteins Receptors, Cytoplasmic and Nuclear - deficiency Receptors, Cytoplasmic and Nuclear - metabolism Signal Transduction - drug effects Sirtuin 1 - metabolism Transcriptome - genetics Up-Regulation |
| title | The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury |
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