Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways
Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-...
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| Veröffentlicht in: | Life sciences (1973) 2020-12, Vol.262, p.118546-10, Article 118546 |
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| container_title | Life sciences (1973) |
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| creator | Li, Zimeng Lian, Yuanyu Wei, Riming Jin, Ling Cao, Houkang Zhao, Tanglian Ma, Xiaohui Zhong, Mingli Gao, Ya Zhang, Kefeng |
| description | Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways. |
| doi_str_mv | 10.1016/j.lfs.2020.118546 |
| format | Article |
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The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2020.118546</identifier><identifier>PMID: 33035580</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Diet ; Diet, High-Fat - adverse effects ; Ethanol ; Ethanol - toxicity ; Heme Oxygenase-1 - metabolism ; Hepatocytes ; High fat diet ; Inflammation ; Inflammation - prevention & control ; Inflammatory response ; Injuries ; Lipid metabolism ; Lipids ; Liver ; Liver Diseases - prevention & control ; Liver Diseases, Alcoholic - prevention & control ; Male ; Membrane Proteins - metabolism ; Metabolism ; Mice ; Mice, Inbred C57BL ; Molecular modelling ; Morphology ; MyD88 protein ; Myeloid Differentiation Factor 88 - metabolism ; NF-E2-Related Factor 2 - metabolism ; NF-kappa B - metabolism ; NF-κB protein ; Nrf2/HO-1 ; Oxidation ; Oxidative stress ; Oxidative Stress - drug effects ; Signal Transduction - drug effects ; Sterols - pharmacology ; Taraxasterol ; TLR4 protein ; TLR4/MyD88/NF-κB ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Triterpenes - pharmacology</subject><ispartof>Life sciences (1973), 2020-12, Vol.262, p.118546-10, Article 118546</ispartof><rights>2020</rights><rights>Copyright © 2020. Published by Elsevier Inc.</rights><rights>Copyright Elsevier BV Dec 1, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-7af62835c1925a79b68167df109374a213b7db8da6e175e9df2539e2393151863</citedby><cites>FETCH-LOGICAL-c381t-7af62835c1925a79b68167df109374a213b7db8da6e175e9df2539e2393151863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320520312996$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33035580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Zimeng</creatorcontrib><creatorcontrib>Lian, Yuanyu</creatorcontrib><creatorcontrib>Wei, Riming</creatorcontrib><creatorcontrib>Jin, Ling</creatorcontrib><creatorcontrib>Cao, Houkang</creatorcontrib><creatorcontrib>Zhao, Tanglian</creatorcontrib><creatorcontrib>Ma, Xiaohui</creatorcontrib><creatorcontrib>Zhong, Mingli</creatorcontrib><creatorcontrib>Gao, Ya</creatorcontrib><creatorcontrib>Zhang, Kefeng</creatorcontrib><title>Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways.</description><subject>Animals</subject><subject>Diet</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Ethanol</subject><subject>Ethanol - toxicity</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hepatocytes</subject><subject>High fat diet</subject><subject>Inflammation</subject><subject>Inflammation - prevention & control</subject><subject>Inflammatory response</subject><subject>Injuries</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver Diseases - prevention & control</subject><subject>Liver Diseases, Alcoholic - prevention & control</subject><subject>Male</subject><subject>Membrane Proteins - metabolism</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular modelling</subject><subject>Morphology</subject><subject>MyD88 protein</subject><subject>Myeloid Differentiation Factor 88 - metabolism</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Nrf2/HO-1</subject><subject>Oxidation</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Signal Transduction - drug effects</subject><subject>Sterols - pharmacology</subject><subject>Taraxasterol</subject><subject>TLR4 protein</subject><subject>TLR4/MyD88/NF-κB</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Triterpenes - pharmacology</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAQxy0EotuPB-CCLHH2rj9ix1FPpbQUaWmlqj1bTmxnHaXJYjuleYq-Tx-CZ8LLFo6cRiP95q-Z-QHwgeAlwUSsumXv4pJimnsieSHegAWRZYWwYOQtWGBMC8Qo5gfgMMYOY8x5yd6DA8Yw41ziBXi-cM42KcLRwaSDftIx2TD2ULfaDzFBmzZ62PWDgRvfbpDTCRpvE_KDmRprYO8fbYB-6KYww3qGwbZTr5MfWni3vi1W3-cvUq6uL9Gvl89_Yq6Do6urG0Rg9O2g-x251WnzU8_xGLxzuo_25LUegfvLi7vzK7S--frt_GyNGiZJQqV2gkrGG1JRrsuqFpKI0jiCK1YWmhJWl6aWRgtLSm4r4yhnlaWsYoQTKdgR-LTP3Ybxx2RjUt04hbxMVLSQlRSCFzJTZE81YYwxWKe2wT_oMCuC1U6B6lRWoHYK1F5Bnvn4mjzVD9b8m_j78wyc7gGb73v0NqjYeDvkV_qQVSgz-v_E_wZWxZYG</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Li, Zimeng</creator><creator>Lian, Yuanyu</creator><creator>Wei, Riming</creator><creator>Jin, Ling</creator><creator>Cao, Houkang</creator><creator>Zhao, Tanglian</creator><creator>Ma, Xiaohui</creator><creator>Zhong, Mingli</creator><creator>Gao, Ya</creator><creator>Zhang, Kefeng</creator><general>Elsevier Inc</general><general>Elsevier BV</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20201201</creationdate><title>Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways</title><author>Li, Zimeng ; Lian, Yuanyu ; Wei, Riming ; Jin, Ling ; Cao, Houkang ; Zhao, Tanglian ; Ma, Xiaohui ; Zhong, Mingli ; Gao, Ya ; Zhang, Kefeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-7af62835c1925a79b68167df109374a213b7db8da6e175e9df2539e2393151863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Diet</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Ethanol</topic><topic>Ethanol - toxicity</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hepatocytes</topic><topic>High fat diet</topic><topic>Inflammation</topic><topic>Inflammation - prevention & control</topic><topic>Inflammatory response</topic><topic>Injuries</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Liver</topic><topic>Liver Diseases - prevention & control</topic><topic>Liver Diseases, Alcoholic - prevention & control</topic><topic>Male</topic><topic>Membrane Proteins - metabolism</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular modelling</topic><topic>Morphology</topic><topic>MyD88 protein</topic><topic>Myeloid Differentiation Factor 88 - metabolism</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Nrf2/HO-1</topic><topic>Oxidation</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Signal Transduction - drug effects</topic><topic>Sterols - pharmacology</topic><topic>Taraxasterol</topic><topic>TLR4 protein</topic><topic>TLR4/MyD88/NF-κB</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Triterpenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Zimeng</creatorcontrib><creatorcontrib>Lian, Yuanyu</creatorcontrib><creatorcontrib>Wei, Riming</creatorcontrib><creatorcontrib>Jin, Ling</creatorcontrib><creatorcontrib>Cao, Houkang</creatorcontrib><creatorcontrib>Zhao, Tanglian</creatorcontrib><creatorcontrib>Ma, Xiaohui</creatorcontrib><creatorcontrib>Zhong, Mingli</creatorcontrib><creatorcontrib>Gao, Ya</creatorcontrib><creatorcontrib>Zhang, Kefeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zimeng</au><au>Lian, Yuanyu</au><au>Wei, Riming</au><au>Jin, Ling</au><au>Cao, Houkang</au><au>Zhao, Tanglian</au><au>Ma, Xiaohui</au><au>Zhong, Mingli</au><au>Gao, Ya</au><au>Zhang, Kefeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>262</volume><spage>118546</spage><epage>10</epage><pages>118546-10</pages><artnum>118546</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Studies have reported that taraxasterol (TAR) is effective in the treatment of immune liver injury and alcoholic liver injury. The mechanism of action is mainly related to the inhibition of inflammation. To determine the key molecular mechanisms for the effect of TAR on alleviating ethanol and high-fat diet-induced liver injury, pathological morphology, biochemistry, oxidative stress, inflammatory response and lipid metabolism were examined. Our results showed that TAR could inhibit ethanol-induced hepatocyte death or lipid accumulation, and suppress oxidative stress, inflammatory response and lipid metabolism disorders. More specifically, ethanol-induced TLR-4 and MyD88 inflammatory response were down-regulated, when treated with TAR. Production of CYP2E1, Nrf2 and HO-1, which produced in response to increased oxidative stress, were regulated in TAR treated, ethanol-induced hepatocytes. In summary, TAR could inhibit the inflammatory response and oxidative stress, which was related to the regulation of TAR on TLR-4/MyD88/NF-κB and Nrf2/HO-1 pathways.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>33035580</pmid><doi>10.1016/j.lfs.2020.118546</doi><tpages>10</tpages></addata></record> |
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| ispartof | Life sciences (1973), 2020-12, Vol.262, p.118546-10, Article 118546 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Diet Diet, High-Fat - adverse effects Ethanol Ethanol - toxicity Heme Oxygenase-1 - metabolism Hepatocytes High fat diet Inflammation Inflammation - prevention & control Inflammatory response Injuries Lipid metabolism Lipids Liver Liver Diseases - prevention & control Liver Diseases, Alcoholic - prevention & control Male Membrane Proteins - metabolism Metabolism Mice Mice, Inbred C57BL Molecular modelling Morphology MyD88 protein Myeloid Differentiation Factor 88 - metabolism NF-E2-Related Factor 2 - metabolism NF-kappa B - metabolism NF-κB protein Nrf2/HO-1 Oxidation Oxidative stress Oxidative Stress - drug effects Signal Transduction - drug effects Sterols - pharmacology Taraxasterol TLR4 protein TLR4/MyD88/NF-κB Toll-Like Receptor 4 - metabolism Toll-like receptors Triterpenes - pharmacology |
| title | Effects of taraxasterol against ethanol and high-fat diet-induced liver injury by regulating TLR4/MyD88/NF-κB and Nrf2/HO-1 signaling pathways |
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