ReferenceID 5531

Isovitexin protects against acute liver injury by targeting PTEN, PI3K and BiP via modification of m6A

Eur J Pharmacol

Isovitexin (IVT) has been shown to have a potential therapeutic effect on acute liver injury (ALI), but its underlying mechanisms especially the targets remain unclear, which was investigated in the present study. Briefl

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Reference Id
5531
Evidence Id
22121
Core Evidence Id
22121
Source Reference Id
4294
Herb2 Reference Id
HBREF005091
Subject Paper Key
HBIN031346_35007522
Pubmed Id
35007522
Doi
10.1016/j.ejphar.2022.174749
Paper Title
Isovitexin protects against acute liver injury by targeting PTEN, PI3K and BiP via modification of m6A
Paper Abstract
Isovitexin (IVT) has been shown to have a potential therapeutic effect on acute liver injury (ALI), but its underlying mechanisms especially the targets remain unclear, which was investigated in the present study. Briefly, the targets of IVT were predicted by bioinformatics and then were verified by multiple examinations using molecular docking, cellular thermal shift assay (CETSA), and Lipopolysaccharide/D-Galactosamine (LPS/D-GalN)-induced ALI animal model. The bioinformatic analysis predicted that the target genes of IVT against ALI were enriched into the PI3K/Akt and ERS-related pathways, in which, molecular docking and CETSA examination verified that the binding sites of IVT likely were PTEN, PI3K and BiP. Furthermore, the possible targets were also verified by animal experiments. The results revealed that IVT significantly ameliorated the hepatic injury, as evidenced by the attenuation of histopathological changes and the reduction in serum aminotransferase and total bilirubin activities. In addition, IVT treatment led to the reduction of PTEN, BiP and ERS-related targets expressions, as well as the elevation of PI3K, Akt and mTOR expressions. Notably, IVT significantly decreased total hepatic m6A level and m6A enrichment of PTEN and BiP, suggesting IVT regulated PTEN and BiP by modulating m6A modification. To sum up, the results indicate that IVT significantly ameliorates ALI, which is attributed to its ability to regulate the PI3K/Akt pathway and ERS by targeting PTEN, PI3K and BiP via modification of m6A. Our finding demonstrates that IVT may be a promising natural medicine for the treatment of ALI.
Journal
Eur J Pharmacol
Publish Year
2022
Experiment Subject
Experiment Type
Animal Experiment
Phenotype Related
Acute Liver Injury
Paper Title Cn
Paper Title En
Isovitexin protects against acute liver injury by targeting PTEN, PI3K and BiP via modification of m6A
Bilingual Status
semi_complete