Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats
► Genistein significantly decrease oxidative stress and production of inflammatory. ► Genistein effectively inhibit fibrogenic mediators and activation of HSCs. ► Genistein could be a possible new therapeutic approach for liver fibrosis. This study examined the effect of genistein isolated from Hydr...
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| Veröffentlicht in: | Toxicology letters 2013-02, Vol.217 (2), p.102-110 |
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| creator | Huang, Quanfang Huang, Renbin Zhang, Shijun Lin, Jun Wei, Ling He, Min Zhuo, Lang Lin, Xing |
| description | ► Genistein significantly decrease oxidative stress and production of inflammatory. ► Genistein effectively inhibit fibrogenic mediators and activation of HSCs. ► Genistein could be a possible new therapeutic approach for liver fibrosis.
This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0–9.5g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-α and myeloperoxidase, via down-regulation of nuclear factor-κB. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of α-smooth muscle actin and transforming growth factor β1 proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats. |
| doi_str_mv | 10.1016/j.toxlet.2012.12.014 |
| format | Article |
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This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0–9.5g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-α and myeloperoxidase, via down-regulation of nuclear factor-κB. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of α-smooth muscle actin and transforming growth factor β1 proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats.</description><identifier>ISSN: 0378-4274</identifier><identifier>EISSN: 1879-3169</identifier><identifier>DOI: 10.1016/j.toxlet.2012.12.014</identifier><identifier>PMID: 23274713</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>Alanine Transaminase - blood ; Alanine Transaminase - metabolism ; Alcohol ; Animals ; Aspartate Aminotransferases - blood ; Aspartate Aminotransferases - metabolism ; Centella - chemistry ; Collagen Type III - metabolism ; Cytochrome P-450 CYP2E1 - metabolism ; Cytokines - blood ; Cytokines - metabolism ; Ethanol - administration & dosage ; Ethanol - blood ; Genistein ; Genistein - isolation & purification ; Genistein - pharmacology ; Histocytochemistry ; Hyaluronic Acid - metabolism ; Hydrocotyle sibthorpioides ; Inflammation - blood ; Inflammation - chemically induced ; Inflammation - enzymology ; Inflammation - metabolism ; Laminin - metabolism ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis, Alcoholic - blood ; Liver Cirrhosis, Alcoholic - metabolism ; Liver Cirrhosis, Alcoholic - pathology ; Liver Cirrhosis, Alcoholic - prevention & control ; Liver fibrosis ; Male ; NF-kappa B - metabolism ; Rats ; Rats, Wistar ; Specific Pathogen-Free Organisms</subject><ispartof>Toxicology letters, 2013-02, Vol.217 (2), p.102-110</ispartof><rights>2012 Elsevier Ireland Ltd</rights><rights>Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-6b46410b497a0e317d938621836ab51b896b3ff780ef2e4164bc5dcf30eaf1283</citedby><cites>FETCH-LOGICAL-c428t-6b46410b497a0e317d938621836ab51b896b3ff780ef2e4164bc5dcf30eaf1283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378427412014439$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23274713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Quanfang</creatorcontrib><creatorcontrib>Huang, Renbin</creatorcontrib><creatorcontrib>Zhang, Shijun</creatorcontrib><creatorcontrib>Lin, Jun</creatorcontrib><creatorcontrib>Wei, Ling</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Zhuo, Lang</creatorcontrib><creatorcontrib>Lin, Xing</creatorcontrib><title>Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats</title><title>Toxicology letters</title><addtitle>Toxicol Lett</addtitle><description>► Genistein significantly decrease oxidative stress and production of inflammatory. ► Genistein effectively inhibit fibrogenic mediators and activation of HSCs. ► Genistein could be a possible new therapeutic approach for liver fibrosis.
This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0–9.5g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-α and myeloperoxidase, via down-regulation of nuclear factor-κB. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of α-smooth muscle actin and transforming growth factor β1 proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats.</description><subject>Alanine Transaminase - blood</subject><subject>Alanine Transaminase - metabolism</subject><subject>Alcohol</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Aspartate Aminotransferases - metabolism</subject><subject>Centella - chemistry</subject><subject>Collagen Type III - metabolism</subject><subject>Cytochrome P-450 CYP2E1 - metabolism</subject><subject>Cytokines - blood</subject><subject>Cytokines - metabolism</subject><subject>Ethanol - administration & dosage</subject><subject>Ethanol - blood</subject><subject>Genistein</subject><subject>Genistein - isolation & purification</subject><subject>Genistein - pharmacology</subject><subject>Histocytochemistry</subject><subject>Hyaluronic Acid - metabolism</subject><subject>Hydrocotyle sibthorpioides</subject><subject>Inflammation - blood</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - enzymology</subject><subject>Inflammation - metabolism</subject><subject>Laminin - metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis, Alcoholic - blood</subject><subject>Liver Cirrhosis, Alcoholic - metabolism</subject><subject>Liver Cirrhosis, Alcoholic - pathology</subject><subject>Liver Cirrhosis, Alcoholic - prevention & control</subject><subject>Liver fibrosis</subject><subject>Male</subject><subject>NF-kappa B - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Specific Pathogen-Free Organisms</subject><issn>0378-4274</issn><issn>1879-3169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kdFqHCEUhqW0NJu0b1CKl72ZjY6u49wUQkiTQKC9aK9FnWPXZXbcqhMyj9C37lk2zWVAUI7f_x_O-Qn5xNmaM64ud-uankao65bxdo2HcfmGrLju-kZw1b8lKyY63ci2k2fkvJQdY0xJtXlPzlqBxY6LFfn7I6cKvsZHoBACvmgK9DdMsVSIE40ljbbCQENOe3q3DDn5VJcRaImublM-xBQHKDRNdAsHW6OncdrNeaF2QlV0OZVYsDbMHm3cQv02pwkxO_q0TSN-0Wxr-UDeBTsW-Ph8X5Bf325-Xt81D99v76-vHhovW10b5aSSnDnZd5aB4N3QC61aroWybsOd7pUTIXSaQWhBciWd3ww-CAY28FaLC_Ll5HvI6c8MpZp9LB7G0U6Q5mKQkegnNUdUnlCPQ5QMwRxy3Nu8GM7MMQSzM6cQzDEElBoMAWWfnzvMbg_Di-j_1hH4egIA53yMkE3xESbcT8yYgBlSfL3DPxuenVk</recordid><startdate>20130227</startdate><enddate>20130227</enddate><creator>Huang, Quanfang</creator><creator>Huang, Renbin</creator><creator>Zhang, Shijun</creator><creator>Lin, Jun</creator><creator>Wei, Ling</creator><creator>He, Min</creator><creator>Zhuo, Lang</creator><creator>Lin, Xing</creator><general>Elsevier Ireland Ltd</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>20130227</creationdate><title>Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats</title><author>Huang, Quanfang ; Huang, Renbin ; Zhang, Shijun ; Lin, Jun ; Wei, Ling ; He, Min ; Zhuo, Lang ; Lin, Xing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-6b46410b497a0e317d938621836ab51b896b3ff780ef2e4164bc5dcf30eaf1283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Alanine Transaminase - blood</topic><topic>Alanine Transaminase - metabolism</topic><topic>Alcohol</topic><topic>Animals</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Aspartate Aminotransferases - metabolism</topic><topic>Centella - chemistry</topic><topic>Collagen Type III - metabolism</topic><topic>Cytochrome P-450 CYP2E1 - metabolism</topic><topic>Cytokines - blood</topic><topic>Cytokines - metabolism</topic><topic>Ethanol - administration & dosage</topic><topic>Ethanol - blood</topic><topic>Genistein</topic><topic>Genistein - isolation & purification</topic><topic>Genistein - pharmacology</topic><topic>Histocytochemistry</topic><topic>Hyaluronic Acid - metabolism</topic><topic>Hydrocotyle sibthorpioides</topic><topic>Inflammation - blood</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - enzymology</topic><topic>Inflammation - metabolism</topic><topic>Laminin - metabolism</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis, Alcoholic - blood</topic><topic>Liver Cirrhosis, Alcoholic - metabolism</topic><topic>Liver Cirrhosis, Alcoholic - pathology</topic><topic>Liver Cirrhosis, Alcoholic - prevention & control</topic><topic>Liver fibrosis</topic><topic>Male</topic><topic>NF-kappa B - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Specific Pathogen-Free Organisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Quanfang</creatorcontrib><creatorcontrib>Huang, Renbin</creatorcontrib><creatorcontrib>Zhang, Shijun</creatorcontrib><creatorcontrib>Lin, Jun</creatorcontrib><creatorcontrib>Wei, Ling</creatorcontrib><creatorcontrib>He, Min</creatorcontrib><creatorcontrib>Zhuo, Lang</creatorcontrib><creatorcontrib>Lin, Xing</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>Toxicology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Quanfang</au><au>Huang, Renbin</au><au>Zhang, Shijun</au><au>Lin, Jun</au><au>Wei, Ling</au><au>He, Min</au><au>Zhuo, Lang</au><au>Lin, Xing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats</atitle><jtitle>Toxicology letters</jtitle><addtitle>Toxicol Lett</addtitle><date>2013-02-27</date><risdate>2013</risdate><volume>217</volume><issue>2</issue><spage>102</spage><epage>110</epage><pages>102-110</pages><issn>0378-4274</issn><eissn>1879-3169</eissn><abstract>► Genistein significantly decrease oxidative stress and production of inflammatory. ► Genistein effectively inhibit fibrogenic mediators and activation of HSCs. ► Genistein could be a possible new therapeutic approach for liver fibrosis.
This study examined the effect of genistein isolated from Hydrocotyle sibthorpioides on chronic alcohol-induced hepatic injury and fibrosis. Rats underwent intragastric administration of alcohol (5.0–9.5g/kg) once a day for 24 weeks. A subset of rats were also intragastrically treated with genistein (0.5, 1 or 2mg/kg) once a day. Genistein significantly decreased the plasma alcohol concentration, inhibited the activities of alanine and aspartate aminotransferases and decreased levels of inflammatory mediators, including interleukin 6, tumor necrosis factor-α and myeloperoxidase, via down-regulation of nuclear factor-κB. Moreover, genistein effectively inhibited collagen deposition and reduced pathological tissue damage as determined by hepatic fibrosis biomarkers, such as total hyaluronic acid, laminin, and type III collagen. Mechanistically, studies showed that genistein markedly reduced lipid peroxidation, recruited the anti-oxidative defense system, inhibited CYP2El activity, promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-2, induced HSC apoptosis by down-regulating B-cell lymphoma 2 mRNA, and inhibited the expression of α-smooth muscle actin and transforming growth factor β1 proteins. In conclusion, genistein exerts a preventative effect to ameliorate developing liver injury and even liver fibrosis induced by chronic alcohol administration in rats.</abstract><cop>Netherlands</cop><pub>Elsevier Ireland Ltd</pub><pmid>23274713</pmid><doi>10.1016/j.toxlet.2012.12.014</doi><tpages>9</tpages></addata></record> |
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| subjects | Alanine Transaminase - blood Alanine Transaminase - metabolism Alcohol Animals Aspartate Aminotransferases - blood Aspartate Aminotransferases - metabolism Centella - chemistry Collagen Type III - metabolism Cytochrome P-450 CYP2E1 - metabolism Cytokines - blood Cytokines - metabolism Ethanol - administration & dosage Ethanol - blood Genistein Genistein - isolation & purification Genistein - pharmacology Histocytochemistry Hyaluronic Acid - metabolism Hydrocotyle sibthorpioides Inflammation - blood Inflammation - chemically induced Inflammation - enzymology Inflammation - metabolism Laminin - metabolism Liver - drug effects Liver - metabolism Liver - pathology Liver Cirrhosis, Alcoholic - blood Liver Cirrhosis, Alcoholic - metabolism Liver Cirrhosis, Alcoholic - pathology Liver Cirrhosis, Alcoholic - prevention & control Liver fibrosis Male NF-kappa B - metabolism Rats Rats, Wistar Specific Pathogen-Free Organisms |
| title | Protective effect of genistein isolated from Hydrocotyle sibthorpioides on hepatic injury and fibrosis induced by chronic alcohol in rats |
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