title: Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver.
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.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology&Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Pingchang
authors.initials: P
authors.lastname: Yang
authors.affiliation: Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microecology, School of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Jieli
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Medical Microecology and Clinical Nutrition Research Institute of Zhengzhou University, Zhengzhou, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage* / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002366:Cassia / Q000737:chemistry*; D002784:Cholesterol / Q000378:metabolism*; D004359:Drug Therapy, Combination; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019936:Probiotics / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000880:Anthraquinones; D015415:Biomarkers; D012333:RNA, Messenger; C042834:9,10-anthraquinone; D002784:Cholesterol