Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine.
Adenosine
/ analogs & derivatives
Animals
Cholesterol
/ metabolism
DNA Methylation
/ drug effects
Diet, High-Fat
/ adverse effects
Fatty Acids, Nonesterified
/ blood
Fatty Liver
/ prevention & control
Liver
/ metabolism
Male
Methylation
/ drug effects
Plant Extracts
/ pharmacology
Rats
Suppressor of Cytokine Signaling Proteins
/ biosynthesis
Transaminases
/ blood
Hepatic steatosis
Ling-gui-zhu-gan decoction
N6-methyladenosine modification
Nonalcoholic fatty liver disease
SOCS2
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
23
11
2019
revised:
15
01
2020
accepted:
27
01
2020
entrez:
21
6
2020
pubmed:
21
6
2020
medline:
17
2
2021
Statut:
ppublish
Résumé
The ling-gui-zhu-gan (LGZG) decoction is a classic formula in traditional chinese medicine (TCM) and is widely used in clinical settings. Recently, the LGZG decoction was demonstrated to have an effect in alleviating hepatic steatosis induced by a high-fat diet (HFD). However, the mechanisms underlying this therapeutic effect remain unclear. The present study was designed to evaluate the effect and explore possible mechanisms of action of the LGZG decoction in nonalcoholic fatty liver disease (NAFLD). Liver tissue and blood samples were harvested. Liver steatosis, triglyceride (TG), liver total cholesterol (TC), liver low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and free fatty acid (FFA) were assayed. N6-methyladenosine (m6A) levels were estimated using an m6A RNA methylation quantification kit and immunohistochemistry. The m6A methylome was detected through methylated RNA immunoprecipitation sequencing (MeRIP-seq), followed by data analysis. The expression levels of differentially methylated genes (DMGs) were determined using real-time polymerase chain reaction and western blotting. The LGZG decoction significantly alleviated hepatic steatosis and reduced m6A levels. MeRIP-seq revealed the coding sequence (CDS) domain to be the most critical modification site for m6A methylation, and the molecular functions of DMGs predominantly included insulin-like growth factor receptor binding and fatty acid metabolism and degradation. Further, LGZG treatment could reduce the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), along with the expression of SOCS2 at mRNA and protein levels. The LGZG decoction is an effective formula for treating NAFLD, and the possible mechanisms underlying its action could be related to N6-methyladenosine modification-medicated SOCS2.
Sections du résumé
BACKGROUND
BACKGROUND
The ling-gui-zhu-gan (LGZG) decoction is a classic formula in traditional chinese medicine (TCM) and is widely used in clinical settings. Recently, the LGZG decoction was demonstrated to have an effect in alleviating hepatic steatosis induced by a high-fat diet (HFD). However, the mechanisms underlying this therapeutic effect remain unclear. The present study was designed to evaluate the effect and explore possible mechanisms of action of the LGZG decoction in nonalcoholic fatty liver disease (NAFLD).
METHODS
METHODS
Liver tissue and blood samples were harvested. Liver steatosis, triglyceride (TG), liver total cholesterol (TC), liver low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and free fatty acid (FFA) were assayed. N6-methyladenosine (m6A) levels were estimated using an m6A RNA methylation quantification kit and immunohistochemistry. The m6A methylome was detected through methylated RNA immunoprecipitation sequencing (MeRIP-seq), followed by data analysis. The expression levels of differentially methylated genes (DMGs) were determined using real-time polymerase chain reaction and western blotting.
RESULTS
RESULTS
The LGZG decoction significantly alleviated hepatic steatosis and reduced m6A levels. MeRIP-seq revealed the coding sequence (CDS) domain to be the most critical modification site for m6A methylation, and the molecular functions of DMGs predominantly included insulin-like growth factor receptor binding and fatty acid metabolism and degradation. Further, LGZG treatment could reduce the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), along with the expression of SOCS2 at mRNA and protein levels.
CONCLUSIONS
CONCLUSIONS
The LGZG decoction is an effective formula for treating NAFLD, and the possible mechanisms underlying its action could be related to N6-methyladenosine modification-medicated SOCS2.
Identifiants
pubmed: 32559839
pii: S0753-3322(20)30166-9
doi: 10.1016/j.biopha.2020.109976
pii:
doi:
Substances chimiques
Fatty Acids, Nonesterified
0
Plant Extracts
0
Socs2 protein, rat
0
Suppressor of Cytokine Signaling Proteins
0
ling-gui-zhu-gan decoction
0
Cholesterol
97C5T2UQ7J
N-methyladenosine
CLE6G00625
Transaminases
EC 2.6.1.-
Adenosine
K72T3FS567
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109976Informations de copyright
Copyright © 2020. Published by Elsevier Masson SAS.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflicts of interest to declare.