Affiliation:
1. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
2. Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China
Abstract
Chebulae Fructus (CF) is a natural medicinal plant widely used for its various pharmacological properties. Natural products used to cure several diseases have been considered safe thanks to their little or no side effects. However, in recent years, a hepatotoxic effect has been found due to the abuse of herbal medicine. CF has been reported to have hepatotoxicity, but the mechanism is unclear. In this experiment, the toxic aspect and mechanism of CF action were evaluated by transcriptome analysis. Components of toxic CF fractions were identified by LC-MS, and hepatotoxic toxic components in toxic CF fractions were predicted by molecular docking. The results showed that the ethyl acetate part of CF was the main toxic fraction, and transcriptome analysis found that the toxic mechanism was highly related to lipid metabolism-related pathways, and CFEA could inhibit the PPAR signaling pathway. Molecular docking results showed that 3′-O-methyl-4-O-(n″-O-galloyl-β-d-xylopyranosyl) ellagic acid (n = 2, 3 or 4) and 4-O-(3″,4″-O-digalloyl-α-l-rhamnosyl) ellagic acid have better docking energies with PPARα protein and FABP protein than other components. In summary, 3′-O-methyl-4-O-(n″-O-galloyl-β-d-xylopyranosyl) ellagic acid (n = 2, 3 or 4) and 4-O-(3″,4″-O-digalloyl-α-l-rhamnosyl) ellagic acid were the main toxic components, which may play a toxic role by inhibiting the PPAR signaling pathway and affect lipid metabolism.
Funder
National Natural Science Foundation of China
Academic Backbone Project of Northeast Agricultural University
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Cited by
1 articles.
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