Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut–Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation
Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut...
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2021-06, Vol.69 (25), p.7074-7083 |
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| container_title | Journal of agricultural and food chemistry |
| container_volume | 69 |
| creator | Yan, Xin Ren, Xueyang Liu, Xiaoyun Wang, Yu Ma, Jiamu Song, Ruolan Wang, Xiuhuan Dong, Ying Fan, Qiqi Wei, Jing Yu, Axiang She, Gaimei |
| description | Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut–liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA. |
| doi_str_mv | 10.1021/acs.jafc.1c02362 |
| format | Article |
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However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut–liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/acs.jafc.1c02362</identifier><identifier>PMID: 34152776</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Bioactive Constituents, Metabolites, and Functions ; Chemical and Drug Induced Liver Injury, Chronic ; Gastrointestinal Microbiome ; Homeostasis ; Liver ; Liver Diseases, Alcoholic - drug therapy ; Liver Diseases, Alcoholic - prevention & control ; Mice ; Triterpenes ; Ursolic Acid</subject><ispartof>Journal of agricultural and food chemistry, 2021-06, Vol.69 (25), p.7074-7083</ispartof><rights>2021 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a336t-ed823a5553702e3780a708de2c79065aa29a6bf877dec0eb1e0322c4fdc2b3d83</citedby><cites>FETCH-LOGICAL-a336t-ed823a5553702e3780a708de2c79065aa29a6bf877dec0eb1e0322c4fdc2b3d83</cites><orcidid>0000-0002-9552-6288</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jafc.1c02362$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jafc.1c02362$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34152776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Xin</creatorcontrib><creatorcontrib>Ren, Xueyang</creatorcontrib><creatorcontrib>Liu, Xiaoyun</creatorcontrib><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Ma, Jiamu</creatorcontrib><creatorcontrib>Song, Ruolan</creatorcontrib><creatorcontrib>Wang, Xiuhuan</creatorcontrib><creatorcontrib>Dong, Ying</creatorcontrib><creatorcontrib>Fan, Qiqi</creatorcontrib><creatorcontrib>Wei, Jing</creatorcontrib><creatorcontrib>Yu, Axiang</creatorcontrib><creatorcontrib>She, Gaimei</creatorcontrib><title>Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut–Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut–liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.</description><subject>Animals</subject><subject>Bioactive Constituents, Metabolites, and Functions</subject><subject>Chemical and Drug Induced Liver Injury, Chronic</subject><subject>Gastrointestinal Microbiome</subject><subject>Homeostasis</subject><subject>Liver</subject><subject>Liver Diseases, Alcoholic - drug therapy</subject><subject>Liver Diseases, Alcoholic - prevention & control</subject><subject>Mice</subject><subject>Triterpenes</subject><subject>Ursolic Acid</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtOwzAQQC0EoqWwZ4V8AFLGdhOn7Cq-Fa1ACNaRY09UV2lcxUlFd9yABTfkJLi0sGNly3pv5HmEnDLoM-DsQmnfn6tC95kGLhK-R7os5hDFjKX7pAuBidI4YR1y5P0cANJYwiHpiEHApEy65OPaYqPqNX2tvSutpiNtDX2qcYVV4-mo1G7mymhcmVajoRO7wpqOq3kblJVV9K5tvt4_t8-jN-vpvVug843y4T51pi1VY111SV9mSB9wTZ9didQVdGp17XIbaDpVlV3uwGNyUKjS48nu7JHX25uXq_to8ng3vhpNIiVE0kRoUi5UHMdCAkchU1ASUoNcyyEksVJ8qJK8SKU0qAFzhiA414PCaJ4Lk4oege3c8AvvayyyZW0XIUTGINu0zULbbNM227UNytlWWbb5As2f8BszAOdb4Ed1bV2FDf6f9w224IiK</recordid><startdate>20210630</startdate><enddate>20210630</enddate><creator>Yan, Xin</creator><creator>Ren, Xueyang</creator><creator>Liu, Xiaoyun</creator><creator>Wang, Yu</creator><creator>Ma, Jiamu</creator><creator>Song, Ruolan</creator><creator>Wang, Xiuhuan</creator><creator>Dong, Ying</creator><creator>Fan, Qiqi</creator><creator>Wei, Jing</creator><creator>Yu, Axiang</creator><creator>She, Gaimei</creator><general>American Chemical Society</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><orcidid>https://orcid.org/0000-0002-9552-6288</orcidid></search><sort><creationdate>20210630</creationdate><title>Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut–Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation</title><author>Yan, Xin ; Ren, Xueyang ; Liu, Xiaoyun ; Wang, Yu ; Ma, Jiamu ; Song, Ruolan ; Wang, Xiuhuan ; Dong, Ying ; Fan, Qiqi ; Wei, Jing ; Yu, Axiang ; She, Gaimei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a336t-ed823a5553702e3780a708de2c79065aa29a6bf877dec0eb1e0322c4fdc2b3d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Bioactive Constituents, Metabolites, and Functions</topic><topic>Chemical and Drug Induced Liver Injury, Chronic</topic><topic>Gastrointestinal Microbiome</topic><topic>Homeostasis</topic><topic>Liver</topic><topic>Liver Diseases, Alcoholic - drug therapy</topic><topic>Liver Diseases, Alcoholic - prevention & control</topic><topic>Mice</topic><topic>Triterpenes</topic><topic>Ursolic Acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yan, Xin</creatorcontrib><creatorcontrib>Ren, Xueyang</creatorcontrib><creatorcontrib>Liu, Xiaoyun</creatorcontrib><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Ma, Jiamu</creatorcontrib><creatorcontrib>Song, Ruolan</creatorcontrib><creatorcontrib>Wang, Xiuhuan</creatorcontrib><creatorcontrib>Dong, Ying</creatorcontrib><creatorcontrib>Fan, Qiqi</creatorcontrib><creatorcontrib>Wei, Jing</creatorcontrib><creatorcontrib>Yu, Axiang</creatorcontrib><creatorcontrib>She, Gaimei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yan, Xin</au><au>Ren, Xueyang</au><au>Liu, Xiaoyun</au><au>Wang, Yu</au><au>Ma, Jiamu</au><au>Song, Ruolan</au><au>Wang, Xiuhuan</au><au>Dong, Ying</au><au>Fan, Qiqi</au><au>Wei, Jing</au><au>Yu, Axiang</au><au>She, Gaimei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut–Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2021-06-30</date><risdate>2021</risdate><volume>69</volume><issue>25</issue><spage>7074</spage><epage>7083</epage><pages>7074-7083</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut–liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. 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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Bioactive Constituents, Metabolites, and Functions Chemical and Drug Induced Liver Injury, Chronic Gastrointestinal Microbiome Homeostasis Liver Liver Diseases, Alcoholic - drug therapy Liver Diseases, Alcoholic - prevention & control Mice Triterpenes Ursolic Acid |
| title | Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut–Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation |
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