Research progress on mechanisms and therapeutic drugs of peroxisome proliferator-activated receptor in treatment of cholestatic liver disease
10.12092/j.issn.1009-2501.2023.07.011
- Author:
Anjing WANG
1
;
Yaya WANG
1
;
Caidong LI
1
;
Anjing WANG
2
;
Yajie YAN
2
;
Jing SU
2
;
Caidong LI
2
;
Xuan LIANG
3
Author Information
1. Department of Pharmacy, the Second People's Hospital of Lanzhou
2. College of Pharmacy, Gansu University of Chinese Medicine
3. College of Veterinary Medicine, Nanjing Agricultural University
- Publication Type:Journal Article
- Keywords:
cholestatic liver disease;
clinical trial;
peroxisome proliferator-activated receptor;
peroxisome proliferator-activated receptor agonist;
therapeutic target
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2023;28(7):796-808
- CountryChina
- Language:Chinese
-
Abstract:
Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.
