UPLC-Q-TOF/MS-Based Metabolomics Approach to Reveal the Hepatotoxicity of Emodin and Detoxification of Dihydromyricetin

Abstract

Dihydromyricetin (DMY), an important flavanone found in Ampelopsis grossedentata, plays a protective role in liver injury. Our previous research found that DMY protected L02 cells against hepatotoxicity caused by emodin. In this study, serum, urine, and liver samples from rats were systematically used for biochemical analysis, pathological observation, and nontargeted metabolomics to evaluate the toxicity of emodin and DMY intervention. After oral administration of DMY, DMY may alleviate liver injury by improving liver metabolism. Approximately, 8 of 15 metabolites in rat urine and serum were significantly regulated by DMY. Metabolic pathway analysis showed that glutathione metabolism, pyrimidine metabolism, and tryptophan metabolism were the most affected pathways, and 18 proteins were predicted to be potential targets of DMY during the alleviation of liver injury induced by emodin. This research is of great significance in confirming the liver-protective effect of DMY, especially during acute liver injury caused by traditional Chinese medicine.

The development and validation of a sensitive HPLC-MS/MS method for the quantitative and pharmacokinetic study of the seven components of Buddleja lindleyana Fort.

“…15,16 Moreover, it has been used to study drug metabolism, [17][18][19][20][21][22] toxicokinetics, 23,24 lipidomics, 25,26 proteomics 27,28 and metabolomics. 29,30 The main advantage of mass spectrometry (MS/MS) is the ability to detect a broad range of drugs with high sensitivity and specicity in a single analytical run. [31][32][33][34] Chemical compounds are recognized by comparing their retention times and parent-daughter ions with those of reference substances.…”

A multifaceted review on dihydromyricetin resources, extraction, bioavailability, biotransformation, bioactivities, and food applications with future perspectives to maximize its value

“…DMY has been showed a protective effect from the emodin‐induced hepatoxicity on the normal human hepatic LO2 cells via the upregulation of Nrf2 and downregulation of CYP7A1 [98]. Besides, metabolomic results of another study revealed that DMY could also reversed the damage of emodin‐induced liver impairment in rats due to the regulation of 18 proteins as well as the metabolism of glutathione, pyrimidine, and tryptophan [110].…”

Metabolic profiling of emodin drug‐induced liver injury and silybin treatment in rats using ultra‐performance liquid chromatography‐quadrupole‐time‐of‐flight‐mass spectrometry: A metabolomic and mechanistic approach

“…Here, we show that the lyPC(20:1) component for glycerophospholipid metabolism decreased with emodin and reversed with silybin treatment. This suggests that silybin could have liver protective effects by regulating appropriate glycerophospholipid metabolism, which was also found for dihydromyricetin (Gao et al, 2021). Again, additional targeted metabolomics research on glycerophospholipid metabolism is required to explain the exact cellular processes for hepatoxicity.…”

“…The rats were divided into three groups (n = 8, each). Group I (control) rats were orally administered an equal volume of distilled water; group II (model) rats were orally administered 1500 mg/kg of emodin every other day (q2D) for 4 weeks; and group III (silybin) rats were orally cotreated with 1500 mg/kg of emodin (Gao et al, 2021;X. Yang et al, 2018) and 100 mg/kg of silybin q2D for 4 weeks (Sun et al, 2020;B.…”

“…Serum and urine samples, 200-μL aliquots, were thawed on ice, and then 800 μL of 100% MeOH (1:4, v/v) was added for deproteinization (Gao et al, 2021). The resulting solution mixture was vortexed for 30 s and centrifuged at 13,000 rpm for 15 min at 4 C. Then, 800 μL of the supernatant was transferred into a new EP tube and dried under nitrogen at 36 C. The resultant dry residue was dissolved in 100 μL of MeOH; the mixture was vortexed for 60 s and centrifuged at 13,000 rpm at 4 C for 15 min; 50 μL of the clear supernatant was transferred into a sampling vial for UPLC-Q-TOF-MS for metabolomic analysis.…”