Effect of dihydromyricetin on hepatic encephalopathy associated with acute hepatic failure in mice

Pharm Biol. 2021 Dec;59(1):557-564. doi: 10.1080/13880209.2021.1917625.

Abstract

Context: Hepatic encephalopathy (HE) is a complex neuropsychiatric disease caused by liver failure. Dihydromyricetin (DMY) is a traditional medicine used to treat liver injury.

Objective: To investigate the effects of dihydromyricetin (DMY) on hepatic encephalopathy associated with acute hepatic failure mice models established by thioacetamide (TAA) exposure.

Materials and methods: Female BALB/c mouse were randomly divided into control, DMY, TAA, and TAA + DMY groups (n = 8). The first two groups were intraperitoneally injected with saline or 5 mg/kg DMY, respectively. The last two groups were injected with 600 mg/kg TAA to establish HE models, and then the mice in the last group were treated with 5 mg/kg DMY. Neurological and cognition functions were evaluated 24 and 48 h after injection. Mice were sacrificed after which livers and brains were obtained for immunoblot and histopathological analysis, while blood was collected for the analysis of liver enzymes.

Results: In the TAA + DMY group, ALT and AST decreased to 145.31 ± 12.88 U/L and 309.51 ± 25.92 U/L, respectively, whereas ammonia and TBIL decreased to 415.67 ± 41.91 μmol/L and 3.31 ± 0.35 μmol/L, respectively. Moreover, MDA decreased to 10.74 ± 3.97 nmol/g, while SOD and GST increased to 398.69 ± 231.30 U/g and 41.37 ± 21.84 U/g, respectively. The neurological score decreased to 2.87 ± 0.63, and the number of GFAP-positive cells decreased to 41.10 ± 1.66. Furthermore, the protein levels of TNF-α, IL-6, and GABAA in the cortex decreased.

Conclusions: We speculate that DMY can serve as a novel treatment for HE.

Keywords: GABAA receptor; Thioacetamide; cognition functions; glial fibrillary acidic protein; liver enzymes.

MeSH terms

  • Animals
  • Female
  • Flavonols / pharmacology
  • Flavonols / therapeutic use*
  • Hepatic Encephalopathy / drug therapy*
  • Hepatic Encephalopathy / metabolism
  • Hepatic Encephalopathy / pathology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Liver Failure, Acute / drug therapy*
  • Liver Failure, Acute / metabolism
  • Liver Failure, Acute / pathology
  • Mice
  • Mice, Inbred BALB C
  • Treatment Outcome

Substances

  • Flavonols
  • dihydromyricetin

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81770525) and Natural Science Foundation of Gansu Province (No. 17JR2JA191, 1506RJZA204 and 20JR5RA339).