Tuihuang Mixture improves α‑naphthylisothiocyanate-induced cholestasis in rats by inhibiting NLRP3 inflammasomes via regulating farnesoid X receptor.
10.12122/j.issn.1673-4254.2025.04.06
- Author:
Zhengwang ZHU
1
;
Linlin WANG
1
;
Jinghan ZHAO
1
;
Ruixue MA
1
;
Yuchun YU
1
;
Qingchun CAI
2
;
Bing WANG
3
;
Pingsheng ZHU
1
;
Mingsan MIAO
1
Author Information
1. First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou 450046, China.
2. Department of Pathology, Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450008, China.
3. Department of Traditional Chinese Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
- Publication Type:Journal Article
- Keywords:
NLRP3 inflammasomes;
Tuihuang Mixture;
cell pyroptosis;
cholestasis;
farnesoid X receptor
- MeSH:
Animals;
NLR Family, Pyrin Domain-Containing 3 Protein;
Rats;
Receptors, Cytoplasmic and Nuclear/metabolism*;
Cholestasis/drug therapy*;
Rats, Wistar;
Inflammasomes/metabolism*;
1-Naphthylisothiocyanate;
Drugs, Chinese Herbal/therapeutic use*;
Male;
Interleukin-18/metabolism*;
Caspase 1/metabolism*;
Interleukin-1beta/metabolism*;
Liver/metabolism*
- From:
Journal of Southern Medical University
2025;45(4):718-724
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To study the therapeutic mechanism of Tuihuang Mixture against cholestasis.
METHODS:Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining.
RESULTS:The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models.
CONCLUSIONS:Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
