In the current study, the therapeutic effectiveness of the
metformin (Met) and
melatonin (Mel) co-loaded
liposomes was investigated on
cholestasis induced by bile duct
ligation (BDL) in male rats. Histopathological analysis, biochemical analysis, and oxidative stress markers were assayed to determine the
therapeutic effect of Met and Mel co-loaded
liposomes on
cholestasis. Histopathological analysis revealed that the simultaneous administration of Met and Mel, whether in the free (
C-Mel-Met) or liposomal (C-Lipo-Mel-Met) forms, reduced
inflammation as well as proliferation of bile ducts; however, results were more prominent in the liposomal form of Mel and Met. Additionaly, serum levels of
aspartate aminotransferase (AST) were significantly (p < 0.001) higher in (
C-Mel-Met) treated rats compared with (BDL) rats; however, (C-Lipo-Mel-Met) treated rats exhibited significant (p < 0.05) lower AST rates in comparison to (BDL) rats. Moreover, a significant (p < 0.0001) drop in
bilirubin levels was detected in (C-Lipo-Mel-Met) treated rats in comparison to (BDL) rats; it is noteworthy mentioning that
bilirubin levels in (C-Lipo-Mel-Met) treated rats were insignificant in comparison to
sham-control (SC) rats. Furthermore, rats concomitantly administered Met and Mel, exhibited significant downregulation in the expression levels of inflammatory
cytokine genes such as TNF-α and
IL-1 gene expression, where the downregulation was more prominent in the liposomal from. Our findings demonestrate that the concomitant administration of
metformin and
melatonin in the liposomal form had more
therapeutic effect on liver injury than their free forms through improving histological changes, reducing
biochemical markers and favoring
oxidant-
antioxidant balance.