Investigation of the idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. through metabolomics using GC-MS

Abstract

Background The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury. Methods Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites. Results The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism. Conclusions These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

“…The level of D-lactic acid changed significantly in the low-dose group after administration for 21 days. Phosphoric acid and glycerol, which are common in liver injury (Lin et al, 2021 ), were significantly changed in the high-dose group, whereas 5-methyluridine in the low-dose group and uridine in the high-dose group were significantly changed, both of which are common metabolites in hepatotoxicity. In conclusion, in terms of dose-dependence, the high-dose group modulated more metabolites on day 10, although the high-dose group modulated fewer metabolites than the low-dose group on day 21, which may due to the smaller number of the samples in the 21-day high-dose group.…”

Concurrent severe hepatotoxicity and agranulocytosis induced by Polygonum multiflorum: A case report

“…PM is widely used in traditional Chinese medicine and dietary supplements; however, it is a major contributor to herbal DILI[ 10 , 11 ]. PM-induced hepatotoxicity occurs only in certain individuals[ 12 ]. PM can induce various types of DILI, such as 59.7%, 15.4%, and 24.9% of hepatocellular, cholestatic, and mixed types, respectively[ 13 ].…”

Lipidomics reveals serum lipid metabolism disorders in CTD-induced liver injury

“…The accumulation of adipose tissue in the liver of mice could disrupt the homeostasis of hepatic metabolism [ 11 ]. Some studies have shown that hepatic injury caused by Polygonum multiflorum , Phytolacca acinosa Roxb and Zhi-Zi-Hou-Po decoction were associated with lipid metabolism disorders [ 12 – 14 ]. Moreover, untargeted metabolomics studies have found that CTD could affect lipid metabolism and induce liver injury by altering the levels of metabolites such as PE (20:5(5Z,8Z,11Z,14Z,17Z)/14:1(9Z)) and oleic acid in mice [ 15 ].…”