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


OBJECTIVE
To further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP.


METHODS
The hepatotoxicity induced by RP and its processed products (PP) (dosed at 20g/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.


RESULTS
RP 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.


CONCLUSIONS
16 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.
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Cong-En
CE
Zhang
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China.
Ming
M
Niu
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China.
Qi
Q
Li
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China.
Yan-Ling
YL
Zhao
Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
Zhi-Jie
ZJ
Ma
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, PR China.
Yin
Y
Xiong
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Xiao-Ping
XP
Dong
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Rui-Yu
RY
Li
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Wu-Wen
WW
Feng
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Qing
Q
Dong
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Xiao
X
Ma
Integrative Medical Center, 302 Military Hospital, Beijing, PR China.
Yun
Y
Zhu
Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, PR China.
Zheng-Sheng
ZS
Zou
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, PR China.
Jun-Ling
JL
Cao
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China. Electronic address: pharm_sci@126.com.
Jia-Bo
JB
Wang
China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China. Electronic address: pharmacy302xxh@126.com.
Xiao-He
XH
Xiao
D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000187:drug effects* / Q000293:injuries; D008516:Medicine, Chinese Traditional / Q000009:adverse effects*; D055432:Metabolomics; D028502:Polygonum / Q000737:chemistry*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D016482:Urinalysis
D015415:Biomarkers
4,6-Dihydroxyquinoline (PubChem CID: 6723); 4-Pyridoxic acid (PubChem CID: 6723); Citrate (PubChem CID: 1198); Indoleacrylic acid (PubChem CID: 440738); L-3-Hydroxykynurenine (PubChem CID: 11811); LC-MS; Liver injury; Metabolomics; Polygonum multiflorum L.; Processed products; Pyridoxamine (PubChem CID: 1052); Urine