Background: Age-associated loss of liver function has been recognized for decades.
But, the mechanism driving liver regeneration and its decline with age remains elusive.
Objective: Hence, to support of our previous studies about anti-aging effects of Ursolic Acid (UA),
a compound which is extensively present in apple peels. The aim of this study is to address whether
UA might alter sensors of the cell metabolic state such as SIRT1, SIRT6, PGC-1β and Klotho proteins.
Methods: To evaluate the effect of UA on hepatic indicated proteins, mice were administrated with
UA twice daily for 7 days. The involvements of these proteins in the UA-mediated effect harmony
hepatic protection were investigated by immunofluorescence microscopy technique.
Results: Our findings clearly illustrated that UA enhanced SIRT1 (~ 5 ± 0.2 folds) and SIRT6 (~ 8
± 0.5 folds) proteins levels in hepatic, p<0.001. In addition, the data showed that UA increased
PGC-1β (~ 7 ± 0.4 folds) protein overexpression, p<0.001. Moreover, we showed that UA upregulated
Klotho (~ 3.5 ± 0.2 folds) protein in order to improve hepatic performance, p<0.01.
Conclusion: Our results suggest that UA through increasing of SIRT1 up-regulation ameliorate reverse
cholesterol transport, fatty acid use and oxidative stress defense. In addition, it seems that UA
by enhancing of SIRT6 expression promotes cholesterol homeostasis through repressing SREBP1
and SREBP2. Reciprocally, UA might be involved in VLDL synthesis and exportation through
PGC-1β up-regulation. Finally, UA might be as key regulators of mineral homeostasis and bile
acid/cholesterol metabolism, by inducing Klotho overexpression.