title: Metabolomics Coupled with Multivariate Data and Pathway Analysis on Potential Biomarkers in Cholestasis and Intervention Effect of Paeonia lactiflora Pall.
abstract: BACKGROUND
  The dried root of Paeonia lactiflora Pall. (PLP) is a classical Chinese herbal medicine that has been used to treat hepatic disease for 1000s of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT-induced cholestasis in rats using a metabolomics approach.
  
  
  METHODS
  The effects of PLP on serum indices (TBIL, DBIL, AST, ALT, ALP, and TBA) and the histopathology of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to identify the possible effect of PLP on metabolites. The pathway analysis was conducted to illustrate the pathways and network by which PLP treats cholestasis.
  
  
  RESULTS
  High-dose PLP remarkably down-regulated the serum indices and alleviated histological damage to the liver. Metabolomics analyses showed that the therapeutic effect of high-dose PLP is mainly associated with the regulation of several metabolites, such as glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, L(D)-arginine, and L-tryptophan. A pathway analysis showed that the metabolites were related to bile acid secretion and amino acid metabolism. In addition, the significant changes in bile acid transporters also indicated that bile acid metabolism might be involved in the therapeutic effect of PLP on cholestasis. Moreover, a principal component analysis indicated that the metabolites in the high-dose PLP group were closer to those of the control, whereas those of the moderate dose or low-dose PLP group were closer to those of the ANIT group. This finding indicated that metabolites may be responsible for the differences between the effects of low-dose and moderate-dose PLP.
  
  
  CONCLUSIONS
  The therapeutic effect of high-dose PLP on cholestasis is possibly related to regulation of bile acid secretion and amino acid metabolism. Moreover, these findings may help better understand the mechanisms of disease and provide a potential therapy for cholestasis.
authors: Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors: Xiao
authors: X
authors: Ma
authors: Cardiology Department, Beijing Chao-Yang Hospital, Capital Medical University Beijing, China.
authors: Yong-Hui
authors: YH
authors: Chi
authors: China Military Institute of Chinese Medicine, 302 Military Hospital of China Beijing, China.
authors: Ming
authors: M
authors: Niu
authors: Department of Integrative Medical Center, 302 Military Hospital of China Beijing, China.
authors: Yun
authors: Y
authors: Zhu
authors: Department of Pharmacy, 302 Military Hospital of China Beijing, China.
authors: Yan-Ling
authors: YL
authors: Zhao
authors: Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors: Zhe
authors: Z
authors: Chen
authors: China Military Institute of Chinese Medicine, 302 Military Hospital of China Beijing, China.
authors: Jia-Bo
authors: JB
authors: Wang
authors: Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China; China Military Institute of Chinese Medicine, 302 Military Hospital of ChinaBeijing, China.
authors: Cong-En
authors: CE
authors: Zhang
authors: Department of Integrative Medical Center, 302 Military Hospital of China Beijing, China.
authors: Jian-Yu
authors: JY
authors: Li
authors: Department of Integrative Medical Center, 302 Military Hospital of China Beijing, China.
authors: Li-Fu
authors: LF
authors: Wang
authors: Department of Integrative Medical Center, 302 Military Hospital of China Beijing, China.
authors: Man
authors: M
authors: Gong
authors: Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors: Shi-Zhang
authors: SZ
authors: Wei
authors: Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors: Chang
authors: C
authors: Chen
authors: Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors: Lu
authors: L
authors: Zhang
authors: Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China; Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors: Ming-Quan
authors: MQ
authors: Wu
authors: China Military Institute of Chinese Medicine, 302 Military Hospital of China Beijing, China.
authors: Xiao-He
authors: XH
authors: Xiao
keywords: Paeonia lactiflora Pall.; bile acid secretion; biomarker; cholestasis; metabolomics