Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver

Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the an...

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Veröffentlicht in:PloS one 2015-09, Vol.10 (9), p.e0138078-e0138078
Hauptverfasser: Mei, Lu, Tang, Youcai, Li, Ming, Yang, Pingchang, Liu, Zhiqiang, Yuan, Jieli, Zheng, Pengyuan
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container_title PloS one
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creator Mei, Lu
Tang, Youcai
Li, Ming
Yang, Pingchang
Liu, Zhiqiang
Yuan, Jieli
Zheng, Pengyuan
description Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.
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Ameliorate Non-Alcoholic Fatty Liver</title><source>PLoS</source><source>MEDLINE</source><source>Full-Text Journals in Chemistry (Open access)</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Mei, Lu ; Tang, Youcai ; Li, Ming ; Yang, Pingchang ; Liu, Zhiqiang ; Yuan, Jieli ; Zheng, Pengyuan</creator><contributor>Alisi, Anna</contributor><creatorcontrib>Mei, Lu ; Tang, Youcai ; Li, Ming ; Yang, Pingchang ; Liu, Zhiqiang ; Yuan, Jieli ; Zheng, Pengyuan ; Alisi, Anna</creatorcontrib><description>Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0138078</identifier><identifier>PMID: 26375281</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ammonium ; Animal models ; Animals ; Anthraquinone ; Anthraquinones - administration &amp; dosage ; Anthraquinones - pharmacology ; Biomarkers - metabolism ; Blotting, Western ; Cassia - chemistry ; Cholesterol ; Cholesterol - metabolism ; Coenzyme A ; Complications and side effects ; Digestive system ; Digestive tract ; Dosage and administration ; Drug therapy ; Drug Therapy, Combination ; Dysbacteriosis ; Fat metabolism ; Fatty liver ; Ferric sulfate ; Functional foods &amp; nutraceuticals ; Gastrointestinal tract ; Gene Expression Profiling ; Health aspects ; High fat diet ; Hydroxylase ; Hydroxymethylglutaryl-CoA reductase ; Insulin resistance ; Intestinal microflora ; Intestine ; Iron sulfates ; Kinases ; Lipid metabolism ; Lipid Metabolism - drug effects ; Lipoprotein (low density) receptors ; Lipoproteins (low density) ; Liver ; Liver diseases ; Low density lipoprotein ; Low density lipoprotein receptors ; Low density lipoproteins ; Male ; Medical treatment ; Metabolism ; Microbiota (Symbiotic organisms) ; mRNA ; Mucosa ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - metabolism ; Non-alcoholic Fatty Liver Disease - pathology ; Normalizing ; Nutrition research ; Patient outcomes ; Peroxisome proliferator-activated receptors ; Physiological aspects ; Probiotics ; Probiotics - administration &amp; dosage ; Probiotics - pharmacology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptor density ; Reductase ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Rodents ; Sulfates</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0138078-e0138078</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Mei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Mei et al 2015 Mei et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-1b97f7fc93ed47dc33935b4634e20880888c1c401dad8efadf43c298d5236c73</citedby><cites>FETCH-LOGICAL-c758t-1b97f7fc93ed47dc33935b4634e20880888c1c401dad8efadf43c298d5236c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573521/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573521/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26375281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Alisi, Anna</contributor><creatorcontrib>Mei, Lu</creatorcontrib><creatorcontrib>Tang, Youcai</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Yang, Pingchang</creatorcontrib><creatorcontrib>Liu, Zhiqiang</creatorcontrib><creatorcontrib>Yuan, Jieli</creatorcontrib><creatorcontrib>Zheng, Pengyuan</creatorcontrib><title>Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.</description><subject>Ammonium</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anthraquinone</subject><subject>Anthraquinones - administration &amp; dosage</subject><subject>Anthraquinones - pharmacology</subject><subject>Biomarkers - metabolism</subject><subject>Blotting, Western</subject><subject>Cassia - chemistry</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Coenzyme A</subject><subject>Complications and side effects</subject><subject>Digestive system</subject><subject>Digestive tract</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Dysbacteriosis</subject><subject>Fat metabolism</subject><subject>Fatty liver</subject><subject>Ferric sulfate</subject><subject>Functional foods &amp; nutraceuticals</subject><subject>Gastrointestinal tract</subject><subject>Gene Expression Profiling</subject><subject>Health aspects</subject><subject>High fat diet</subject><subject>Hydroxylase</subject><subject>Hydroxymethylglutaryl-CoA reductase</subject><subject>Insulin resistance</subject><subject>Intestinal microflora</subject><subject>Intestine</subject><subject>Iron sulfates</subject><subject>Kinases</subject><subject>Lipid metabolism</subject><subject>Lipid Metabolism - drug effects</subject><subject>Lipoprotein (low density) receptors</subject><subject>Lipoproteins (low density)</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Low density lipoprotein</subject><subject>Low density lipoprotein receptors</subject><subject>Low density lipoproteins</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Metabolism</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>mRNA</subject><subject>Mucosa</subject><subject>Non-alcoholic Fatty Liver Disease - drug therapy</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Non-alcoholic Fatty Liver Disease - metabolism</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Normalizing</subject><subject>Nutrition research</subject><subject>Patient outcomes</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Physiological aspects</subject><subject>Probiotics</subject><subject>Probiotics - administration &amp; 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Ameliorate Non-Alcoholic Fatty Liver</title><author>Mei, Lu ; Tang, Youcai ; Li, Ming ; Yang, Pingchang ; Liu, Zhiqiang ; Yuan, Jieli ; Zheng, Pengyuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-1b97f7fc93ed47dc33935b4634e20880888c1c401dad8efadf43c298d5236c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Ammonium</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anthraquinone</topic><topic>Anthraquinones - administration &amp; dosage</topic><topic>Anthraquinones - pharmacology</topic><topic>Biomarkers - metabolism</topic><topic>Blotting, Western</topic><topic>Cassia - chemistry</topic><topic>Cholesterol</topic><topic>Cholesterol - metabolism</topic><topic>Coenzyme A</topic><topic>Complications and side effects</topic><topic>Digestive system</topic><topic>Digestive tract</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Dysbacteriosis</topic><topic>Fat metabolism</topic><topic>Fatty liver</topic><topic>Ferric sulfate</topic><topic>Functional foods &amp; nutraceuticals</topic><topic>Gastrointestinal tract</topic><topic>Gene Expression Profiling</topic><topic>Health aspects</topic><topic>High fat diet</topic><topic>Hydroxylase</topic><topic>Hydroxymethylglutaryl-CoA reductase</topic><topic>Insulin resistance</topic><topic>Intestinal microflora</topic><topic>Intestine</topic><topic>Iron sulfates</topic><topic>Kinases</topic><topic>Lipid metabolism</topic><topic>Lipid Metabolism - drug effects</topic><topic>Lipoprotein (low density) receptors</topic><topic>Lipoproteins (low density)</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Low density lipoprotein</topic><topic>Low density lipoprotein receptors</topic><topic>Low density lipoproteins</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Metabolism</topic><topic>Microbiota (Symbiotic organisms)</topic><topic>mRNA</topic><topic>Mucosa</topic><topic>Non-alcoholic Fatty Liver Disease - drug therapy</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Non-alcoholic Fatty Liver Disease - metabolism</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Normalizing</topic><topic>Nutrition research</topic><topic>Patient outcomes</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Physiological aspects</topic><topic>Probiotics</topic><topic>Probiotics - administration &amp; 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Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content (ProQuest)</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mei, Lu</au><au>Tang, Youcai</au><au>Li, Ming</au><au>Yang, Pingchang</au><au>Liu, Zhiqiang</au><au>Yuan, Jieli</au><au>Zheng, Pengyuan</au><au>Alisi, Anna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-16</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0138078</spage><epage>e0138078</epage><pages>e0138078-e0138078</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26375281</pmid><doi>10.1371/journal.pone.0138078</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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issn 1932-6203
1932-6203
language eng
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subjects Ammonium
Animal models
Animals
Anthraquinone
Anthraquinones - administration & dosage
Anthraquinones - pharmacology
Biomarkers - metabolism
Blotting, Western
Cassia - chemistry
Cholesterol
Cholesterol - metabolism
Coenzyme A
Complications and side effects
Digestive system
Digestive tract
Dosage and administration
Drug therapy
Drug Therapy, Combination
Dysbacteriosis
Fat metabolism
Fatty liver
Ferric sulfate
Functional foods & nutraceuticals
Gastrointestinal tract
Gene Expression Profiling
Health aspects
High fat diet
Hydroxylase
Hydroxymethylglutaryl-CoA reductase
Insulin resistance
Intestinal microflora
Intestine
Iron sulfates
Kinases
Lipid metabolism
Lipid Metabolism - drug effects
Lipoprotein (low density) receptors
Lipoproteins (low density)
Liver
Liver diseases
Low density lipoprotein
Low density lipoprotein receptors
Low density lipoproteins
Male
Medical treatment
Metabolism
Microbiota (Symbiotic organisms)
mRNA
Mucosa
Non-alcoholic Fatty Liver Disease - drug therapy
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Normalizing
Nutrition research
Patient outcomes
Peroxisome proliferator-activated receptors
Physiological aspects
Probiotics
Probiotics - administration & dosage
Probiotics - pharmacology
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
Receptor density
Reductase
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Rodents
Sulfates
title Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver
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