Urine metabolomics study on the liver injury in rats induced by raw and processed Polygonum multiflorum integrated with pattern recognition and pathways analysis

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• 作者：Cong-en Zhang^a ; ^b ; ¹ ; Ming Niu^a ; ¹ ; Qi Li^a ; ¹ ; Yan-ling Zhao^a ; Zhi-jie Ma^c ; Yin Xiong^g ; Xiao-ping Dong^b ; Rui-yu Li^a ; ^b ; Wu-wen Feng^a ; ^b ; Qing Dong^a ; ^b ; Xiao Ma^a ; ^b ; Yun Zhu^f ; Zheng-sheng Zou^d ; Jun-ling Cao^e ; Jia-bo Wang^a ; ^{pharm_sci@126.com} ; Xiao-he Xiao^a ; ^{pharmacy302xxh@126.com}
• 关键词：RP ; Raw Polygonum multiflorum L ; PP ; Processed Polygonum multiflorum L ; HPLC-MS ; high performance liquid chromatography-mass spectrometry ; PCA ; principal component analysis ; PLS-DA ; partial least squares discriminant analysis ; VIP ; variable importance parameters ; DILI ; drug-induced liver injury ; ALT ; alanine aminotransferase ; AST ; aspartate aminotransferase ; γ-GT ; γ-glutamyl transferase ; ALP ; alkaline phosphatase ; ALB ; albumin ; TBIL ; total bilirubin ; DBIL ; direct bilirubin ; I-BiL ; indirect bilir
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：24 December 2016
• 年：2016
• 卷：194
• 期：Complete
• 页码：299-306
• 全文大小：2084 K
• 卷排序：194

文摘

Polygonum multiflorum L. is a famous traditional Chinese medicine that has always been perceived to be safe. Recently, the increasing case reports on hepatotoxicity induced by Raw P. multiflorum (RP) have attracted particular attention. However, the diagnosis and identification of RP-induced hepatotoxicity are still very difficult for its unknown mechanism and the lack of specific biomarkers.Aim of the studyTo further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP.Materials and methodsThe hepatotoxicity induced by RP and its processed products (PP) (dosed at 20 g/kg for 4 weeks) on rats were investigated using conventional approaches including the biochemical analysis and histopathological observations. Further, a urinary metabolomic approach was developed to study the metabolic disturbances caused by RP and PP, followed by the pattern recognition approach and pathways analysis.ResultsRP showed obvious hepatotoxity whereas PP did not. 16 potential biomarkers (pyridoxamine, 4-pyridoxic acid, citrate et al.) differentially expressed in RP group were identified compared with the control and PP-treated groups. The pathways analysis showed that vitamin B6 metabolism, tryptophan metabolism and citrate cycle might be the major enriched pathways involved in the hepatotoxicity of the herb.Conclusion16 differentially expressed metabolites were identified to be involved in the RP-induced hepatotoxicity. Vitamin B6 metabolism might be mostly related to the hepatotoxicity induced by RP. This finding may provide a potential therapeutic target or option to treat hepatotoxicity induced by RP.