Polyene phosphatidyl choline injection regulates lipid homeostasis via AKT-PDE3-PKA in mice

Alcoholic liver disease (ALD) remains a major global health challenge, necessitating effective therapeutic interventions. Polyene phosphatidyl choline (PPC) has shown potential in liver disorders, yet its clinical efficacy and molecular mechanisms in ALD require further validation. This study aimed to assess the clinical effectiveness of PPC using real-world data and to elucidate its hepatoprotective mechanisms in a murine ALD model.

Clinical efficacy was evaluated via retrospective data analysis, focusing on PPC's effects on liver injury and lipid metabolism biomarkers. A mouse model of alcoholic liver injury was established, and PPC's protective effects were investigated using biochemical assays and histopathology. RNA-sequencing identified differentially expressed genes and pathways, with key targets validated by Western blot.

Clinical analysis showed PPC significantly improved liver function and lipid parameters in ALD patients. In mice, PPC alleviated alcohol-induced hepatic inflammation, oxidative stress, and lipid accumulation. RNA-seq indicated involvement of the Akt-PDE3-PKA axis, and Western blot confirmed PPC downregulated Akt1, Traf3, Prkaca, and NF-κB p65 while upregulating Pde3b. Histopathology consistently revealed reduced steatosis and liver damage.

In conclusion, PPC injections exert clinically meaningful hepatoprotective effects, likely through regulation of the Akt-PDE3-PKA pathway to modulate lipid homeostasis in ALD.