Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation
Abstract Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigate...
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2017
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oai:doaj.org-article:9a2bafc487e94da097d5f878413fc9982021-12-02T15:06:09ZDose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation10.1038/s41598-017-09131-22045-2322https://doaj.org/article/9a2bafc487e94da097d5f878413fc9982017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09131-2https://doaj.org/toc/2045-2322Abstract Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage.Jingzhuo TianJingjing ZhuYan YiChunying LiYushi ZhangYong ZhaoChen PanShixie XiangXiaolong LiGuiqin LiJohn W NewmanXiaoyi FengJing LiuJiayin HanLianmei WangYue GaoMichael R. La FranoAihua LiangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Jingzhuo Tian Jingjing Zhu Yan Yi Chunying Li Yushi Zhang Yong Zhao Chen Pan Shixie Xiang Xiaolong Li Guiqin Li John W Newman Xiaoyi Feng Jing Liu Jiayin Han Lianmei Wang Yue Gao Michael R. La Frano Aihua Liang Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation |
| description |
Abstract Fructus Gardenia (FG), containing the major active constituent Geniposide, is widely used in China for medicinal purposes. Currently, clinical reports of FG toxicity have not been published, however, animal studies have shown FG or Geniposide can cause hepatotoxicity in rats. We investigated Geniposide-induced hepatic injury in male Sprague-Dawley rats after 3-day intragastric administration of 100 mg/kg or 300 mg/kg Geniposide. Changes in hepatic histomorphology, serum liver enzyme, serum and hepatic bile acid profiles, and hepatic bile acid synthesis and transportation gene expression were measured. The 300 mg/kg Geniposide caused liver injury evidenced by pathological changes and increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamytransferase (γ-GT). While liver, but not sera, total bile acids (TBAs) were increased 75% by this dose, dominated by increases in taurine-conjugated bile acids (t-CBAs). The 300 mg/kg Geniposide also down-regulated expression of Farnesoid X receptor (FXR), small heterodimer partner (SHP) and bile salt export pump (BSEP). In conclusion, 300 mg/kg Geniposide can induce liver injury with associated changes in bile acid regulating genes, leading to an accumulation of taurine conjugates in the rat liver. Taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) as well as tauro-α-muricholic acid (T-α-MCA) are potential markers for Geniposide-induced hepatic damage. |
| format |
article |
| author |
Jingzhuo Tian Jingjing Zhu Yan Yi Chunying Li Yushi Zhang Yong Zhao Chen Pan Shixie Xiang Xiaolong Li Guiqin Li John W Newman Xiaoyi Feng Jing Liu Jiayin Han Lianmei Wang Yue Gao Michael R. La Frano Aihua Liang |
| author_facet |
Jingzhuo Tian Jingjing Zhu Yan Yi Chunying Li Yushi Zhang Yong Zhao Chen Pan Shixie Xiang Xiaolong Li Guiqin Li John W Newman Xiaoyi Feng Jing Liu Jiayin Han Lianmei Wang Yue Gao Michael R. La Frano Aihua Liang |
| author_sort |
Jingzhuo Tian |
| title |
Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation |
| title_short |
Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation |
| title_full |
Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation |
| title_fullStr |
Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation |
| title_full_unstemmed |
Dose-related liver injury of Geniposide associated with the alteration in bile acid synthesis and transportation |
| title_sort |
dose-related liver injury of geniposide associated with the alteration in bile acid synthesis and transportation |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/9a2bafc487e94da097d5f878413fc998 |
| work_keys_str_mv |
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