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Urine metabolomics study on the liver injury in rats induced by raw and processed Polygonum multiflorum integrated
Cong-En Zhang1, Ming Niu2, Qi Li2
1China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China.
Ethnopharmacological Relevance:
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 Study:
To further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP.
Materials And 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.
Conclusion:
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.
Insights
Raw Polygonum multiflorum (RP) causes liver damage, unlike its processed form. Researchers identified 16 urinary biomarkers and found vitamin B6 metabolism is key to RP-induced hepatotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Metabolomics
Background:
- Polygonum multiflorum L. is a traditional Chinese medicine.
- Recent reports link Raw P. multiflorum (RP) to hepatotoxicity.
- RP-induced liver injury lacks clear diagnostic markers and understanding of its mechanism.
Purpose of the Study:
- Investigate the toxicity of RP and its processed products (PP).
- Elucidate the metabolic mechanisms underlying RP-induced hepatotoxicity.
Main Methods:
- Rats were treated with RP and PP (20g/kg for 4 weeks).
- Biochemical analysis and histopathology assessed liver injury.
- Urinary metabolomics identified biomarkers and metabolic pathways.
Main Results:
- RP induced significant hepatotoxicity; PP did not.
- 16 differential metabolites (e.g., pyridoxamine, 4-pyridoxic acid) were identified in the RP group.
- Vitamin B6 metabolism, tryptophan metabolism, and the citrate cycle were implicated.
Conclusions:
- 16 metabolites are linked to RP-induced hepatotoxicity.
- Vitamin B6 metabolism is a primary pathway involved.
- Findings may offer therapeutic targets for RP-induced liver injury.
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