Hepatoprotective effects of geniposide in a rat model of nonalcoholic steatohepatitis

Objectives  Nonalcoholic steatohepatitis (NASH), a metabolic disorder of the liver, may gradually evolve into fibrosis or cirrhosis. Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide...

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Veröffentlicht in:Journal of pharmacy and pharmacology 2011-04, Vol.63 (4), p.587-593
Hauptverfasser: Ma, Taotao, Huang, Cheng, Zong, Guojun, Zha, Dajun, Meng, Xiaoming, Li, Jun, Tang, Wenjian
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container_end_page 593
container_issue 4
container_start_page 587
container_title Journal of pharmacy and pharmacology
container_volume 63
creator Ma, Taotao
Huang, Cheng
Zong, Guojun
Zha, Dajun
Meng, Xiaoming
Li, Jun
Tang, Wenjian
description Objectives  Nonalcoholic steatohepatitis (NASH), a metabolic disorder of the liver, may gradually evolve into fibrosis or cirrhosis. Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. Methods  Male Sprague–Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. Key findings  Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide‐treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor‐α level in high‐fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator‐activated receptor‐α (PPARα) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. Conclusions  Geniposide exerts protective effects against hepatic steatosis in rats fed with a high fat diet; the underlying mechanism may be associated with its antioxidant actions or regulation of adipocytokine release and expression of PPARα.
doi_str_mv 10.1111/j.2042-7158.2011.01256.x
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Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. Methods  Male Sprague–Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. Key findings  Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide‐treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor‐α level in high‐fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator‐activated receptor‐α (PPARα) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. Conclusions  Geniposide exerts protective effects against hepatic steatosis in rats fed with a high fat diet; the underlying mechanism may be associated with its antioxidant actions or regulation of adipocytokine release and expression of PPARα.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/j.2042-7158.2011.01256.x</identifier><identifier>PMID: 21401612</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Alanine Transaminase - blood ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Aspartate Aminotransferases - blood ; Cytochrome P-450 CYP2E1 - biosynthesis ; Dietary Fats - adverse effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Fatty Liver - etiology ; Fatty Liver - metabolism ; Fatty Liver - prevention &amp; control ; geniposide ; Insulin - blood ; Iridoids - pharmacology ; Iridoids - therapeutic use ; Lipid Metabolism - drug effects ; lipid peroxidation ; Male ; Malondialdehyde - metabolism ; Non-alcoholic Fatty Liver Disease ; non-alcoholic steatohepatitis (NASH) ; PPAR alpha - biosynthesis ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase - metabolism ; Tumor Necrosis Factor-alpha - blood</subject><ispartof>Journal of pharmacy and pharmacology, 2011-04, Vol.63 (4), p.587-593</ispartof><rights>2011 The Authors. 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Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. Methods  Male Sprague–Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. Key findings  Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide‐treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor‐α level in high‐fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator‐activated receptor‐α (PPARα) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. 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Huang, Cheng ; Zong, Guojun ; Zha, Dajun ; Meng, Xiaoming ; Li, Jun ; Tang, Wenjian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5236-f195030cc184289034c4e6dd5e03338fbe84b05ab217838cd96cb88ccf3088f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alanine Transaminase - blood</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Cytochrome P-450 CYP2E1 - biosynthesis</topic><topic>Dietary Fats - adverse effects</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical</topic><topic>Fatty Liver - etiology</topic><topic>Fatty Liver - metabolism</topic><topic>Fatty Liver - prevention &amp; control</topic><topic>geniposide</topic><topic>Insulin - blood</topic><topic>Iridoids - pharmacology</topic><topic>Iridoids - therapeutic use</topic><topic>Lipid Metabolism - drug effects</topic><topic>lipid peroxidation</topic><topic>Male</topic><topic>Malondialdehyde - metabolism</topic><topic>Non-alcoholic Fatty Liver Disease</topic><topic>non-alcoholic steatohepatitis (NASH)</topic><topic>PPAR alpha - biosynthesis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Tumor Necrosis Factor-alpha - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Taotao</creatorcontrib><creatorcontrib>Huang, Cheng</creatorcontrib><creatorcontrib>Zong, Guojun</creatorcontrib><creatorcontrib>Zha, Dajun</creatorcontrib><creatorcontrib>Meng, Xiaoming</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Tang, Wenjian</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Taotao</au><au>Huang, Cheng</au><au>Zong, Guojun</au><au>Zha, Dajun</au><au>Meng, Xiaoming</au><au>Li, Jun</au><au>Tang, Wenjian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatoprotective effects of geniposide in a rat model of nonalcoholic steatohepatitis</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2011-04</date><risdate>2011</risdate><volume>63</volume><issue>4</issue><spage>587</spage><epage>593</epage><pages>587-593</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><abstract>Objectives  Nonalcoholic steatohepatitis (NASH), a metabolic disorder of the liver, may gradually evolve into fibrosis or cirrhosis. Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. Methods  Male Sprague–Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. Key findings  Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide‐treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor‐α level in high‐fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator‐activated receptor‐α (PPARα) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. Conclusions  Geniposide exerts protective effects against hepatic steatosis in rats fed with a high fat diet; the underlying mechanism may be associated with its antioxidant actions or regulation of adipocytokine release and expression of PPARα.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21401612</pmid><doi>10.1111/j.2042-7158.2011.01256.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Alanine Transaminase - blood
Animals
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Aspartate Aminotransferases - blood
Cytochrome P-450 CYP2E1 - biosynthesis
Dietary Fats - adverse effects
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Fatty Liver - etiology
Fatty Liver - metabolism
Fatty Liver - prevention & control
geniposide
Insulin - blood
Iridoids - pharmacology
Iridoids - therapeutic use
Lipid Metabolism - drug effects
lipid peroxidation
Male
Malondialdehyde - metabolism
Non-alcoholic Fatty Liver Disease
non-alcoholic steatohepatitis (NASH)
PPAR alpha - biosynthesis
Rats
Rats, Sprague-Dawley
Superoxide Dismutase - metabolism
Tumor Necrosis Factor-alpha - blood
title Hepatoprotective effects of geniposide in a rat model of nonalcoholic steatohepatitis
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