Background:

IC50: N/A

DLPC is an LRH-1 agonist ligand.

The orphan nuclear receptor liver receptor homolog-1 (LRH-1) is recognized as a critical regulator of bile salt biosynthesis. Bile salts are recognized increasingly as modulators of glucose and lipid metabolism in both human and animals.

In vitro: In a cell-free system, DLPC specifically bound to a recombinant LRH-1 ligand-binding domain. At functional level, DLPC was found to be a strong activator of both human and mouse LRH-1, while other nuclear receptors including FXR, CAR, PXR, PPARa and PPARc were all unaffected by DLPC in cell culture. In addition, DLPC induced the transactivation of the native mouse Shp and Oct4 promoters, consistent with previous studies on Lrh-1. In HepG2 cell line, DLPC could induce the expression of CYP8B1 [1].

In vivo: In mouse in vivo test, DLPC induced bile acid biosynthetic enzymes in mouse liver, lowered hepatic triglycerides and serum glucose, and increased bile acid levels. Moreover, DLPC treatment was also able to decrease hepatic steatosis and improve glucose homeostasis in two mouse models of insulin resistance [1].

Clinical trial: In a previous clinical study, single-dose inhalations of liposome preparations of Bec-DLPC and DLPC alone were administered. Results showed that no adverse clinical or laboratory events were observed. Thus, it was concluded that DLPC liposome aerosol was well tolerated in doses equivalent to those administered by MDIs for treatment of asthma [2].

参考文献:
[1] Hohenester S,Beuers U.  Phosphatidylcholines as regulators of glucose and lipid homeostasis: promises and potential risks. Hepatology.2011 Dec;54(6):2265-7.
[2] Waldrep JC,Gilbert BE,Knight CM,Black MB,Scherer PW,Knight V,Eschenbacher W. Pulmonary delivery of beclomethasone liposome aerosol in volunteers. Tolerance and safety. Chest.1997 Feb;111(2):316-23.