Abstract
The root of Reynoutria multiflora (Thunb.) Moldenke (syn.: Polygonum multiflorum Thunb., HSW) is a distinguished herb that has been popularly used in traditional Chinese medicine (TCM). Evidence of its potential side effect on liver injury has accumulated and received much attention. The objective of this study was to profile the metabolic characteristics of lipids in injured liver of rats induced by HSW and to find out potential lipid biomarkers of toxic consequence. A lipopolysaccharide (LPS)-induced rat model of idiosyncratic drug-induced liver injury (IDILI) was constructed and evident liver injury caused by HSW was confirmed based on the combination of biochemical, morphological, and functional tests. A lipidomics method was developed for the first time to investigate the alteration of lipid metabolism in HSW-induced IDILI rat liver by using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry coupled with multivariate analysis. A total of 202 characterized lipids, including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), phosphatidylinositol (PI), lysophosphatidylinositol (LPI), phosphatidylserine (PS), phosphoglycerols (PG), and ceramide (Cer), were compared among groups of LPS and LPS + HSW. A total of 14 out 26 LPC, 22 out of 47 PC, 19 out of 29 LPE, 16 out of 36 PE, and 10 out of 15 PI species were increased in HSW-treated rat liver, which indicated that HSW may cause liver damage via interfering the phospholipid metabolism. The present work may assist lipid biomarker development of HSW-induced DILI and it also provide new insights into the relationships between phospholipid perturbation and herbal-induced idiosyncratic DILI.
Highlights
Herbal therapies, originated from traditional Chinese medicine (TCM), Indian Ayurvedic medicine, and other traditional medicines, have received increasing attention for their remarkable therapeutic properties; there is simultaneously growing concern about the increase in their potential side effect
Based on the high resolution precursor ions and their characteristic fragment ions, the 16 main peaks were identified as citric acid, procyanidin B, gambiriin A, mono-Ogalloylprocyanidin, 2,3,5,4′-tetrahydroxy -silbence-2,3-glucoside, 2,3,5,4′-tetrahydroxysilbence, 2,3,5,4′-tetrahydroxysilbence-2 -(galloyl)-glucoside, 2,3,5,4′-tetrahydroxysilbence-2-(acetyl)glucoside, 2,3,5,4′ -tetrahydroxysilbence-2-(galloyl)-glucoside, citreorosein-O-glucoside, 2,3,5,4′-tetra -hydroxy silbence-2(coumaro-yl)-glucoside, 2,3,5,4′-tetrahydroxysilbence- -glucoside, torachrysone-8-O-glucoside, emodin-8-O-glucoside, emodin-8-O-(6′-O -malonyl)-glucoside, and emodin, respectively
Substantial liver damage caused by HSW in an LPSinduced rat model was confirmed by combination of an integrated morphological test, histological assessment, and biomedical analysis
Summary
Herbal therapies, originated from traditional Chinese medicine (TCM), Indian Ayurvedic medicine, and other traditional medicines, have received increasing attention for their remarkable therapeutic properties; there is simultaneously growing concern about the increase in their potential side effect. A mild immune-stimulated idiosyncratic DILI rodent model induced by bacterial lipopolysaccharide (LPS) has been created and applied to evaluation idiosyncratic DILI properties of some drugs and herbs (Liguori et al, 2010). Untargeted metabolomics studies (Li et al, 2016; Tu et al, 2019) have indicated that HSWinduced liver injury altered glycerophospholipid metabolism, the tricarboxylic acid cycle, and sphingolipid metabolism in the LPS induced IDILI rat model. These studies implied that lipid metabolism disorder might be involved in HSW-induced liver injury
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