Targeting RXFP1 by Ligustilide: A novel therapeutic approach for alcoholic hepatic steatosis.

Alcoholic hepatic steatosis Inflammatory response Ligustilide Lipid metabolism RXFP1

Journal

International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259

Informations de publication

Date de publication:
28 Dec 2023
Historique:
received: 24 11 2023
revised: 21 12 2023
accepted: 25 12 2023
medline: 2 1 2024
pubmed: 2 1 2024
entrez: 29 12 2023
Statut: aheadofprint

Résumé

Ligustilide (Lig) is the main active ingredient of Umbelliferae Angelicae Sinensis Radix (Chinese Angelica) and Chuanxiong Rhizoma (Sichuan lovase rhizome). Lig possesses various pharmacological properties and could treat obesity by regulating energy metabolism. However, the impact and regulatory mechanism of Lig on alcoholic hepatic steatosis remains unclear. This study aimed to explore the therapeutic effect of Lig on alcoholic hepatic steatosis and its related pharmacological mechanism. With chronic and binge ethanol feeding, liver tissue damage and lipid accumulation in mice suffering alcoholic hepatic steatosis were significantly improved after Lig treatment. Lig effectively regulated the expression levels of lipid metabolism-related proteins in alcoholic hepatic steatosis. In addition, Lig reduced RXFP1 expression, inhibited the activation of NLRP3 inflammasome, and blocked NET formation. Lig reduced the infiltration of immune cells to the liver and the further prevented the occurrence of alcohol-stimulated inflammatory response in liver. Lig significantly regulated lipid accumulation in alcohol exposed AML12 cells via modulating PPARα and SREBP1. In MPMs, Lig decreased the expression of RXFP1, inhibited the activation of NLRP3 in macrophages stimulated by LPS/ATP, and slowed down the occurrence of inflammatory response. Lig sustained lipid metabolism homeostasis in alcoholic hepatic steatosis, through inhibiting the activation of NLRP3 inflammasomes and the formation of NETs, especially targeting RXFP1 in macrophages.

Sections du résumé

BACKGROUND BACKGROUND
Ligustilide (Lig) is the main active ingredient of Umbelliferae Angelicae Sinensis Radix (Chinese Angelica) and Chuanxiong Rhizoma (Sichuan lovase rhizome). Lig possesses various pharmacological properties and could treat obesity by regulating energy metabolism. However, the impact and regulatory mechanism of Lig on alcoholic hepatic steatosis remains unclear.
PURPOSE OBJECTIVE
This study aimed to explore the therapeutic effect of Lig on alcoholic hepatic steatosis and its related pharmacological mechanism.
RESULTS RESULTS
With chronic and binge ethanol feeding, liver tissue damage and lipid accumulation in mice suffering alcoholic hepatic steatosis were significantly improved after Lig treatment. Lig effectively regulated the expression levels of lipid metabolism-related proteins in alcoholic hepatic steatosis. In addition, Lig reduced RXFP1 expression, inhibited the activation of NLRP3 inflammasome, and blocked NET formation. Lig reduced the infiltration of immune cells to the liver and the further prevented the occurrence of alcohol-stimulated inflammatory response in liver. Lig significantly regulated lipid accumulation in alcohol exposed AML12 cells via modulating PPARα and SREBP1. In MPMs, Lig decreased the expression of RXFP1, inhibited the activation of NLRP3 in macrophages stimulated by LPS/ATP, and slowed down the occurrence of inflammatory response.
CONCLUSION CONCLUSIONS
Lig sustained lipid metabolism homeostasis in alcoholic hepatic steatosis, through inhibiting the activation of NLRP3 inflammasomes and the formation of NETs, especially targeting RXFP1 in macrophages.

Identifiants

DOI: 10.1016/j.intimp.2023.111460 PMID: 38157696
pubmed: 38157696
pii: S1567-5769(23)01787-3
doi: 10.1016/j.intimp.2023.111460
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

111460

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Hong-Xu Yang (HX)

Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University) of State Ethnic Affairs Commission, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.

Xue-Li Jiang (XL)

Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University) of State Ethnic Affairs Commission, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.

Rong-Mei Zuo (RM)

Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University) of State Ethnic Affairs Commission, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.

Yan-Ling Wu (YL)

Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University) of State Ethnic Affairs Commission, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.

Ji-Xing Nan (JX)

Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University) of State Ethnic Affairs Commission, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China. Electronic address: jxnan@ybu.edu.cn.

Li-Hua Lian (LH)

Key Laboratory of Traditional Chinese Korean Medicine Research (Yanbian University) of State Ethnic Affairs Commission, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China. Electronic address: lhlian@ybu.edu.cn.

Classifications MeSH