The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats
The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from Potentilla chinensis against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The re...
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| Veröffentlicht in: | Inflammation 2022-08, Vol.45 (4), p.1780-1799 |
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| creator | Chen, Siyun Huang, Yushen Su, Hongmei Zhu, Wuchang Wei, Yuanyuan Long, Yan Shi, Yanxia Wei, Jinbin |
| description | The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from
Potentilla chinensis
against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid significantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid significantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP
+
/NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of apoptosis-related protein. Moreover, Asiatic acid could regulate the Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and inflammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid inhibited the gene expression of Gpat3 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis. |
| doi_str_mv | 10.1007/s10753-022-01660-x |
| format | Article |
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Potentilla chinensis
against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid significantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid significantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP
+
/NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of apoptosis-related protein. Moreover, Asiatic acid could regulate the Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and inflammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid inhibited the gene expression of Gpat3 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.</description><identifier>ISSN: 0360-3997</identifier><identifier>EISSN: 1573-2576</identifier><identifier>DOI: 10.1007/s10753-022-01660-x</identifier><identifier>PMID: 35348973</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Acids ; Alcohol ; Animals ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Ethanol - pharmacology ; Gene expression ; Glycerol ; Glycerophospholipids - metabolism ; Glycerophospholipids - pharmacology ; Hepatitis ; Hepatitis, Alcoholic - drug therapy ; Hepatitis, Alcoholic - metabolism ; Hepatitis, Alcoholic - pathology ; Immunology ; Internal Medicine ; Lecithin ; Liver - metabolism ; Metabolism ; Metabolites ; Metabolomics ; NADP ; NF-E2-Related Factor 2 - metabolism ; NF-kappa B - metabolism ; NF-κB protein ; Original Article ; Oxidative Stress ; Pathology ; Pentacyclic Triterpenes ; Pharmacology/Toxicology ; Phosphatidylcholine ; Phosphatidylethanolamine ; Phosphatidylserine ; Phosphocholine ; Rats ; Rheumatology ; Signal transduction ; Transcriptome ; Transcriptomics</subject><ispartof>Inflammation, 2022-08, Vol.45 (4), p.1780-1799</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c349t-9836a6b13b1aed9d088a5ea17cb318e5886b2d37bb03ddddcba1a16e323bbc433</citedby><cites>FETCH-LOGICAL-c349t-9836a6b13b1aed9d088a5ea17cb318e5886b2d37bb03ddddcba1a16e323bbc433</cites><orcidid>0000-0002-6813-6428</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10753-022-01660-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10753-022-01660-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35348973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Siyun</creatorcontrib><creatorcontrib>Huang, Yushen</creatorcontrib><creatorcontrib>Su, Hongmei</creatorcontrib><creatorcontrib>Zhu, Wuchang</creatorcontrib><creatorcontrib>Wei, Yuanyuan</creatorcontrib><creatorcontrib>Long, Yan</creatorcontrib><creatorcontrib>Shi, Yanxia</creatorcontrib><creatorcontrib>Wei, Jinbin</creatorcontrib><title>The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats</title><title>Inflammation</title><addtitle>Inflammation</addtitle><addtitle>Inflammation</addtitle><description>The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from
Potentilla chinensis
against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid significantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid significantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP
+
/NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of apoptosis-related protein. Moreover, Asiatic acid could regulate the Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and inflammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid inhibited the gene expression of Gpat3 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.</description><subject>Acids</subject><subject>Alcohol</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Ethanol - pharmacology</subject><subject>Gene expression</subject><subject>Glycerol</subject><subject>Glycerophospholipids - metabolism</subject><subject>Glycerophospholipids - pharmacology</subject><subject>Hepatitis</subject><subject>Hepatitis, Alcoholic - drug therapy</subject><subject>Hepatitis, Alcoholic - metabolism</subject><subject>Hepatitis, Alcoholic - pathology</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Lecithin</subject><subject>Liver - metabolism</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>NADP</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Original Article</subject><subject>Oxidative Stress</subject><subject>Pathology</subject><subject>Pentacyclic Triterpenes</subject><subject>Pharmacology/Toxicology</subject><subject>Phosphatidylcholine</subject><subject>Phosphatidylethanolamine</subject><subject>Phosphatidylserine</subject><subject>Phosphocholine</subject><subject>Rats</subject><subject>Rheumatology</subject><subject>Signal transduction</subject><subject>Transcriptome</subject><subject>Transcriptomics</subject><issn>0360-3997</issn><issn>1573-2576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFu1TAQRS0Eoo_CD7BAltiwCdhxYifLqCq0UhESel1bY2fSuvKLg-2g9hv4afxIAYkF3li6c-aOZi4hrzl7zxlTHxJnqhUVq-uKcSlZdf-E7HirRFW3Sj4lOyaKKPpenZAXKd0xxrq-E8_JiWhF0_VK7MiP_S3SyznjTYSMIx1m8A_JJRomuo8wJxvdksPB2URhHulnzGCC34Tr-Ts6n2guHsUnwoJrdhY8PZ8mtPloMiQHRaODdSMNMx28DbfBF-UCl1LJZZab6VfI6SV5NoFP-OrxPyXXH8_3ZxfV1ZdPl2fDVWVF0-eqrCBBGi4MBxz7kXUdtAhcWSN4h23XSVOPQhnDxFieNcCBSxS1MMY2QpySd5vvEsO3FVPWB5cseg8zhjXpWjZN39SskQV9-w96F9ZYbnSklCy3LZcvVL1RNoaUIk56ie4A8UFzpo9R6S0qXaLSv6LS96XpzaP1ag44_mn5nU0BxAakUppvMP6d_R_bn28VoUE</recordid><startdate>20220801</startdate><enddate>20220801</enddate><creator>Chen, Siyun</creator><creator>Huang, Yushen</creator><creator>Su, Hongmei</creator><creator>Zhu, Wuchang</creator><creator>Wei, Yuanyuan</creator><creator>Long, Yan</creator><creator>Shi, Yanxia</creator><creator>Wei, Jinbin</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6813-6428</orcidid></search><sort><creationdate>20220801</creationdate><title>The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats</title><author>Chen, Siyun ; Huang, Yushen ; Su, Hongmei ; Zhu, Wuchang ; Wei, Yuanyuan ; Long, Yan ; Shi, Yanxia ; Wei, Jinbin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c349t-9836a6b13b1aed9d088a5ea17cb318e5886b2d37bb03ddddcba1a16e323bbc433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acids</topic><topic>Alcohol</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Ethanol - pharmacology</topic><topic>Gene expression</topic><topic>Glycerol</topic><topic>Glycerophospholipids - metabolism</topic><topic>Glycerophospholipids - pharmacology</topic><topic>Hepatitis</topic><topic>Hepatitis, Alcoholic - drug therapy</topic><topic>Hepatitis, Alcoholic - metabolism</topic><topic>Hepatitis, Alcoholic - pathology</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Lecithin</topic><topic>Liver - metabolism</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>NADP</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Original Article</topic><topic>Oxidative Stress</topic><topic>Pathology</topic><topic>Pentacyclic Triterpenes</topic><topic>Pharmacology/Toxicology</topic><topic>Phosphatidylcholine</topic><topic>Phosphatidylethanolamine</topic><topic>Phosphatidylserine</topic><topic>Phosphocholine</topic><topic>Rats</topic><topic>Rheumatology</topic><topic>Signal transduction</topic><topic>Transcriptome</topic><topic>Transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Siyun</creatorcontrib><creatorcontrib>Huang, Yushen</creatorcontrib><creatorcontrib>Su, Hongmei</creatorcontrib><creatorcontrib>Zhu, Wuchang</creatorcontrib><creatorcontrib>Wei, Yuanyuan</creatorcontrib><creatorcontrib>Long, Yan</creatorcontrib><creatorcontrib>Shi, Yanxia</creatorcontrib><creatorcontrib>Wei, Jinbin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Inflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Siyun</au><au>Huang, Yushen</au><au>Su, Hongmei</au><au>Zhu, Wuchang</au><au>Wei, Yuanyuan</au><au>Long, Yan</au><au>Shi, Yanxia</au><au>Wei, Jinbin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats</atitle><jtitle>Inflammation</jtitle><stitle>Inflammation</stitle><addtitle>Inflammation</addtitle><date>2022-08-01</date><risdate>2022</risdate><volume>45</volume><issue>4</issue><spage>1780</spage><epage>1799</epage><pages>1780-1799</pages><issn>0360-3997</issn><eissn>1573-2576</eissn><abstract>The present study was to investigate the therapeutical effects and mechanisms of Asiatic acid from
Potentilla chinensis
against alcoholic hepatitis. Rats were intragastrically fed with alcohol for 12 weeks to induce alcoholic hepatitis and then treated with various drugs for further 12 weeks. The results showed that Asiatic acid significantly alleviated liver injury caused by alcohol in rats, as evidenced by the improved histological changes and the lower levels of AST, ALT, and TBIL. Besides, Asiatic acid significantly enhanced the activity of ADH and ALDH, promoting alcohol metabolism. Asiatic acid suppressed CYP2E1 activity and NADP
+
/NADPH ratio, resulting in low ROS production. Further study revealed that Asiatic acid markedly reduced hepatocyte apoptosis by regulating the expression levels of apoptosis-related protein. Moreover, Asiatic acid could regulate the Nrf2 and NF-κB signaling pathway, attenuating oxidative stress and inflammation as a result. Interestingly, the comprehensive analysis of transcriptomics and metabolomics indicated that Asiatic acid inhibited the gene expression of Gpat3 and thereby affected the biosynthesis of the metabolites (1-acyl-Sn-glycerol-3-phosphocholine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine), regulating the glycerophospholipid metabolism pathway and ultimately ameliorating hepatocyte damage. In conclusion, this study demonstrates that Asiatic acid can ameliorate alcoholic hepatitis by modulating the NF-κB and Nrf2 signaling pathways and the glycerophospholipid metabolism pathway, which may be developed as a potential medicine for the treatment of alcoholic hepatitis.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35348973</pmid><doi>10.1007/s10753-022-01660-x</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0002-6813-6428</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Alcohol Animals Apoptosis Biomedical and Life Sciences Biomedicine Ethanol - pharmacology Gene expression Glycerol Glycerophospholipids - metabolism Glycerophospholipids - pharmacology Hepatitis Hepatitis, Alcoholic - drug therapy Hepatitis, Alcoholic - metabolism Hepatitis, Alcoholic - pathology Immunology Internal Medicine Lecithin Liver - metabolism Metabolism Metabolites Metabolomics NADP NF-E2-Related Factor 2 - metabolism NF-kappa B - metabolism NF-κB protein Original Article Oxidative Stress Pathology Pentacyclic Triterpenes Pharmacology/Toxicology Phosphatidylcholine Phosphatidylethanolamine Phosphatidylserine Phosphocholine Rats Rheumatology Signal transduction Transcriptome Transcriptomics |
| title | The Integrated Analysis of Transcriptomics and Metabolomics Unveils the Therapeutical Effect of Asiatic Acid on Alcoholic Hepatitis in Rats |
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