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Background: Cholestatic liver diseases , including primary cholangitis, primary sclerosing cholangitis, and estrogen-induced cholestasis, may progress to liver fibrosis, cirrhosis, and even liver cancer if treatment is delayed
Cholestatic liver disease Cholestatic liver disease TLR4/MyD88/NF-κB TLR4/MyD88/NF-κB PXR/CAR PXR/CAR
Paeoniflorin (PF) , a monoterpene glycoside compound, is beneficial in improving nonalcoholic fatty liver disease, liver I/R injury, arthritis and cholestatic liver disease, but its low bioavailability greatly limits clinical application
Paeoniflorin (PF) Paeoniflorin (PF) Phospholipid (PL) Phospholipid (PL) Phospholipid Complex (PLC) Phospholipid Complex (PLC)
OBJECTIVE: On the basis of previous studies, PF-PLC micelles were first prepared to study their protective effect on 17α-ethinyl estradiol (EE)-induced cholestatic liver injury in rats, and finally from inflammation and nuclear receptor/metabolism.
Inflammation Inflammation Nuclear Receptor/Metabolic Enzyme Nuclear Receptor/Metabolic Enzyme
Methods: PF-PLC micelles were prepared and characterized
Liver Histopathology Liver Histopathology Inflammatory Cytokines Inflammatory Cytokines Inflammation-related Pathway Proteins Immunofluorescence Staining Immunofluorescence Staining Immunohistochemistry Immunohistochemistry
Results: Compared with PF-PLC, PF-PLC micelles had better sustained release effect
Serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acids (TBA) in EE-induced cholestasis rats were higher than those in controls, and PF and PF-PLC micelle treatment reduced these indicators
Mechanistic studies showed that PF-PLC micelle treatment could inhibit the TLR4/MyD88/NF-κB pathway and further reduce the level of pro-inflammatory factors
Conclusion: These results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease, and provide a scientific experimental basis for the clinical development of a novel PF hepatoprotective drug delivery system
PF-PLC micelles have great potential in the treatment of cholestatic liver disease
Source:
Yuan, T.
Yuan, T.
, Lv, S.
, Zhang, W.
, et al.
(2022).
PF-PLC micelles ameliorate cholestatic liver injury via regulating TLR4/MyD88/NF-κB and PXR/CAR/UGT1A1 signaling pathways in EE- induced rats.
International journal of pharmaceutics, 615, 121480.
Advance online publication.
https://doi.
org/10.
1016/j.
ijpharm.
2022.
121480
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