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. 2015 Oct 2:6:217.
doi: 10.3389/fphar.2015.00217. eCollection 2015.

Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study

Qin Dong  1 , Na Li  2 , Qi Li  2 , Cong-En Zhang  1 , Wu-Wen Feng  1 , Guang-Quan Li  1 , Rui-Yu Li  1 , Can Tu  2 , Xue Han  1 , Zhao-Fang Bai  2 , Ya-Ming Zhang  2 , Ming Niu  2 , Zhi-Jie Ma  3 , Xiao-He Xiao  4 , Jia-Bo Wang  2
Affiliations

Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study

Qin Dong et al. Front Pharmacol. .

Abstract

Heshouwu (HSW), the dry roots of Polygonum multiflorum, a classical traditional Chinese medicine is used as a tonic for a wide range of conditions, particularly those associated with aging. However, it tends to be taken overdose or long term in these years, which has resulted in liver damage reported in many countries. In this study, the indicative roles of nine bile acids (BAs) were evaluated to offer potential biomarkers for HSW induced liver injury. Nine BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA), and hyodeoxycholic acid (HDCA) in rat bile and serum were detected by a developed LC-MS method after 42 days treatment. Partial least square-discriminate analysis (PLS-DA) was applied to evaluate the indicative roles of the nine BAs, and metabolism of the nine BAs was summarized. Significant change was observed for the concentrations of nine BAs in treatment groups compared with normal control; In the PLS-DA plots of nine BAs in bile, normal control and raw HSW groups were separately clustered and could be clearly distinguished, GDCA was selected as the distinguished components for raw HSW overdose treatment group. In the PLS-DA plots of nine BAs in serum, the normal control and raw HSW overdose treatment group were separately clustered and could be clearly distinguished, and HDCA was selected as the distinguished components for raw HSW overdose treatment group. The results indicated the perturbation of nine BAs was associated with HSW induced liver injury; GDCA in bile, as well as HDCA in serum could be selected as potential biomarkers for HSW induced liver injury; it also laid the foundation for the further search on the mechanisms of liver injury induced by HSW.

Keywords: LC-MS; Polygonum multiflorum; bile acid; biomarker; liver injury.

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Figures

Figure 1
Figure 1
LC/MS/MS chromatograms of nine bile acids.
Figure 2
Figure 2
PLS-DA clusters based on the quantitative analysis of BAs in rat bile and serum (n = 6) from different treatment groups in negative ESI mode.
Figure 3
Figure 3
Discrimination of normal control rats from raw HSW, processed HSW and chlorpromazine treatment rats according to PLS-DA. (A–C) Discriminations based on the quantitative analysis of BAs in rat bile. (D–F) Discriminations based on the quantitative analysis of BAs in rat serum.
Figure 4
Figure 4
Loading plots of PLS-DA between normal control group and raw HSW overdose treatment group, processed HSW overdose treatment group, chlorpromazine treatment group, respectively. Loading plots of PLS-DA between normal control group and raw HSW overdose treatment group based on bile acids in rat bile (A) and rat serum (D). Loading plots of PLS-DA between normal control group and processed HSW overdose treatment group based on bile acids in rat bile (B) and rat serum (E). Loading plots of PLS-DA between normal control group and chlorpromazine treatment group based on bile acids in rat bile (C) and rat serum (F). Blue triangles were BAs with VIP > 1 in the model.
Figure 5
Figure 5
Bile acids metabolism in liver and intestine. The bar graphs show the differences of concentrations of BAs between four groups, and the concentrations of BAs in normal control group were set as 1 as the control. N, P, R, and C represent the normal control, processed HSW, raw HSW and chlorpromazine group separately. **P ≤ 0.01; *P ≤ 0.05, significantly change was observed when compared with normal control.
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