Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice

[Display omitted] •The therapeutic effect of baicalin (BA) on MCD-induced NAFLD was confirmed.•BA treatment reduced MCD-induced hepatic inflammatory response.•BA protect mice against MCD-induced NAFLD via suppression of TLR4 signaling pathway.•Baicalin-loaded nanoliposomes was found to be more effec...

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Veröffentlicht in:International immunopharmacology 2020-03, Vol.80, p.106208, Article 106208
Hauptverfasser: Liu, Jin, Yuan, Yinglin, Gong, Xia, Zhang, Liangke, Zhou, Qin, Wu, Shengwang, Zhang, Xue, Hu, Jun, Kuang, Ge, Yin, Xinru, Wan, Jingyuan, Yuan, Yonghua
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container_title International immunopharmacology
container_volume 80
creator Liu, Jin
Yuan, Yinglin
Gong, Xia
Zhang, Liangke
Zhou, Qin
Wu, Shengwang
Zhang, Xue
Hu, Jun
Kuang, Ge
Yin, Xinru
Wan, Jingyuan
Yuan, Yonghua
description [Display omitted] •The therapeutic effect of baicalin (BA) on MCD-induced NAFLD was confirmed.•BA treatment reduced MCD-induced hepatic inflammatory response.•BA protect mice against MCD-induced NAFLD via suppression of TLR4 signaling pathway.•Baicalin-loaded nanoliposomes was found to be more effective than BA.•Nanoliposomes is a promising carrier to baicalin for future applications. As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.
doi_str_mv 10.1016/j.intimp.2020.106208
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As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2020.106208</identifier><identifier>PMID: 31955065</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Anti-inflammatory agents ; Apoptosis ; Baicalin ; Bioavailability ; Choline ; Choline Deficiency ; Cytokines - genetics ; Diet ; Drug Liberation ; Fatty liver ; Fibrosis ; Flavonoids ; Flavonoids - administration &amp; dosage ; Flavonoids - chemistry ; Inflammation ; Leukocytes (neutrophilic) ; Lipids ; Liposomes ; Liver ; Liver - drug effects ; Liver - immunology ; Liver - pathology ; Liver diseases ; Macrophages ; Male ; Methionine ; Methionine - deficiency ; Mice, Inbred C57BL ; Nanoliposomes ; Nanoparticles - administration &amp; dosage ; Nanoparticles - chemistry ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - immunology ; Non-alcoholic Fatty Liver Disease - pathology ; Nonalcoholic fatty liver disease ; Nutrient deficiency ; Signaling ; TLR4 protein ; Toll-like receptor 4 ; Toll-Like Receptor 4 - antagonists &amp; inhibitors ; Toll-Like Receptor 4 - immunology ; Toll-like receptors ; Transaminase</subject><ispartof>International immunopharmacology, 2020-03, Vol.80, p.106208, Article 106208</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Mar 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-36155b559266df63ddaa451381f722d632c84875ef64a42adecc68e99ef660dc3</citedby><cites>FETCH-LOGICAL-c390t-36155b559266df63ddaa451381f722d632c84875ef64a42adecc68e99ef660dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1567576919325482$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31955065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Jin</creatorcontrib><creatorcontrib>Yuan, Yinglin</creatorcontrib><creatorcontrib>Gong, Xia</creatorcontrib><creatorcontrib>Zhang, Liangke</creatorcontrib><creatorcontrib>Zhou, Qin</creatorcontrib><creatorcontrib>Wu, Shengwang</creatorcontrib><creatorcontrib>Zhang, Xue</creatorcontrib><creatorcontrib>Hu, Jun</creatorcontrib><creatorcontrib>Kuang, Ge</creatorcontrib><creatorcontrib>Yin, Xinru</creatorcontrib><creatorcontrib>Wan, Jingyuan</creatorcontrib><creatorcontrib>Yuan, Yonghua</creatorcontrib><title>Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>[Display omitted] •The therapeutic effect of baicalin (BA) on MCD-induced NAFLD was confirmed.•BA treatment reduced MCD-induced hepatic inflammatory response.•BA protect mice against MCD-induced NAFLD via suppression of TLR4 signaling pathway.•Baicalin-loaded nanoliposomes was found to be more effective than BA.•Nanoliposomes is a promising carrier to baicalin for future applications. As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.</description><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Apoptosis</subject><subject>Baicalin</subject><subject>Bioavailability</subject><subject>Choline</subject><subject>Choline Deficiency</subject><subject>Cytokines - genetics</subject><subject>Diet</subject><subject>Drug Liberation</subject><subject>Fatty liver</subject><subject>Fibrosis</subject><subject>Flavonoids</subject><subject>Flavonoids - administration &amp; dosage</subject><subject>Flavonoids - chemistry</subject><subject>Inflammation</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipids</subject><subject>Liposomes</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - immunology</subject><subject>Liver - pathology</subject><subject>Liver diseases</subject><subject>Macrophages</subject><subject>Male</subject><subject>Methionine</subject><subject>Methionine - deficiency</subject><subject>Mice, Inbred C57BL</subject><subject>Nanoliposomes</subject><subject>Nanoparticles - administration &amp; dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Non-alcoholic Fatty Liver Disease - drug therapy</subject><subject>Non-alcoholic Fatty Liver Disease - immunology</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Nonalcoholic fatty liver disease</subject><subject>Nutrient deficiency</subject><subject>Signaling</subject><subject>TLR4 protein</subject><subject>Toll-like receptor 4</subject><subject>Toll-Like Receptor 4 - antagonists &amp; inhibitors</subject><subject>Toll-Like Receptor 4 - immunology</subject><subject>Toll-like receptors</subject><subject>Transaminase</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE-LFDEQxYMo7rr6DUQCnntM0km6-yLo4j8YEGQ9h2xSvdbQnbSpnoE9-N03Q68ePVXx8qpe6sfYayl2Ukj77rDDtOK87JRQZ8kq0T9hl7Lv-kZ2wjytvbFdYzo7XLAXRAchqq7lc3bRysEYYc0l-_PRY_ATJu5T5LgSTz7lCZdMeQbifoYJc_Fr7VNOfgr5V30OfPTres8nPEHhEQk8AT-h53RclgJEmBPPI7_Z_9Cc8C6dM-548BR8BF7zZgzwkj0b_UTw6rFesZ-fP91cf2323798u_6wb0I7iLVprTTm1phBWRtH28bovTay7eXYKRVtq0Kv-87AaLXXqgaEYHsYhipYEUN7xd5ue5eSfx-BVnfIx1L_RE5pLU3XSttXl95coWSiAqNbCs6-3Dsp3Jm5O7iNuTszdxvzOvbmcfnxdob4b-gv5Gp4vxmgnnhCKI4CQgoQsUBYXcz4_4QHqL-V_A</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Liu, Jin</creator><creator>Yuan, Yinglin</creator><creator>Gong, Xia</creator><creator>Zhang, Liangke</creator><creator>Zhou, Qin</creator><creator>Wu, Shengwang</creator><creator>Zhang, Xue</creator><creator>Hu, Jun</creator><creator>Kuang, Ge</creator><creator>Yin, Xinru</creator><creator>Wan, Jingyuan</creator><creator>Yuan, Yonghua</creator><general>Elsevier B.V</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>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>202003</creationdate><title>Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice</title><author>Liu, Jin ; Yuan, Yinglin ; Gong, Xia ; Zhang, Liangke ; Zhou, Qin ; Wu, Shengwang ; Zhang, Xue ; Hu, Jun ; Kuang, Ge ; Yin, Xinru ; Wan, Jingyuan ; Yuan, Yonghua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-36155b559266df63ddaa451381f722d632c84875ef64a42adecc68e99ef660dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Anti-inflammatory agents</topic><topic>Apoptosis</topic><topic>Baicalin</topic><topic>Bioavailability</topic><topic>Choline</topic><topic>Choline Deficiency</topic><topic>Cytokines - genetics</topic><topic>Diet</topic><topic>Drug Liberation</topic><topic>Fatty liver</topic><topic>Fibrosis</topic><topic>Flavonoids</topic><topic>Flavonoids - administration &amp; dosage</topic><topic>Flavonoids - chemistry</topic><topic>Inflammation</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lipids</topic><topic>Liposomes</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - immunology</topic><topic>Liver - pathology</topic><topic>Liver diseases</topic><topic>Macrophages</topic><topic>Male</topic><topic>Methionine</topic><topic>Methionine - deficiency</topic><topic>Mice, Inbred C57BL</topic><topic>Nanoliposomes</topic><topic>Nanoparticles - administration &amp; dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Non-alcoholic Fatty Liver Disease - drug therapy</topic><topic>Non-alcoholic Fatty Liver Disease - immunology</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Nonalcoholic fatty liver disease</topic><topic>Nutrient deficiency</topic><topic>Signaling</topic><topic>TLR4 protein</topic><topic>Toll-like receptor 4</topic><topic>Toll-Like Receptor 4 - antagonists &amp; inhibitors</topic><topic>Toll-Like Receptor 4 - immunology</topic><topic>Toll-like receptors</topic><topic>Transaminase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jin</creatorcontrib><creatorcontrib>Yuan, Yinglin</creatorcontrib><creatorcontrib>Gong, Xia</creatorcontrib><creatorcontrib>Zhang, Liangke</creatorcontrib><creatorcontrib>Zhou, Qin</creatorcontrib><creatorcontrib>Wu, Shengwang</creatorcontrib><creatorcontrib>Zhang, Xue</creatorcontrib><creatorcontrib>Hu, Jun</creatorcontrib><creatorcontrib>Kuang, Ge</creatorcontrib><creatorcontrib>Yin, Xinru</creatorcontrib><creatorcontrib>Wan, Jingyuan</creatorcontrib><creatorcontrib>Yuan, Yonghua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology 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><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Jin</au><au>Yuan, Yinglin</au><au>Gong, Xia</au><au>Zhang, Liangke</au><au>Zhou, Qin</au><au>Wu, Shengwang</au><au>Zhang, Xue</au><au>Hu, Jun</au><au>Kuang, Ge</au><au>Yin, Xinru</au><au>Wan, Jingyuan</au><au>Yuan, Yonghua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2020-03</date><risdate>2020</risdate><volume>80</volume><spage>106208</spage><pages>106208-</pages><artnum>106208</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>[Display omitted] •The therapeutic effect of baicalin (BA) on MCD-induced NAFLD was confirmed.•BA treatment reduced MCD-induced hepatic inflammatory response.•BA protect mice against MCD-induced NAFLD via suppression of TLR4 signaling pathway.•Baicalin-loaded nanoliposomes was found to be more effective than BA.•Nanoliposomes is a promising carrier to baicalin for future applications. As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31955065</pmid><doi>10.1016/j.intimp.2020.106208</doi></addata></record>
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subjects Animals
Anti-inflammatory agents
Apoptosis
Baicalin
Bioavailability
Choline
Choline Deficiency
Cytokines - genetics
Diet
Drug Liberation
Fatty liver
Fibrosis
Flavonoids
Flavonoids - administration & dosage
Flavonoids - chemistry
Inflammation
Leukocytes (neutrophilic)
Lipids
Liposomes
Liver
Liver - drug effects
Liver - immunology
Liver - pathology
Liver diseases
Macrophages
Male
Methionine
Methionine - deficiency
Mice, Inbred C57BL
Nanoliposomes
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Non-alcoholic Fatty Liver Disease - drug therapy
Non-alcoholic Fatty Liver Disease - immunology
Non-alcoholic Fatty Liver Disease - pathology
Nonalcoholic fatty liver disease
Nutrient deficiency
Signaling
TLR4 protein
Toll-like receptor 4
Toll-Like Receptor 4 - antagonists & inhibitors
Toll-Like Receptor 4 - immunology
Toll-like receptors
Transaminase
title Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice
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