The effects of Honokiol on the liver of Alzheimer's disease mice by upregulating SIRT3

BackgroundWe demonstrated that Honokiol (HKL), a natural compound from <i>Magnolia officinalis</i>, exerts neuroprotection in APP/PS1 mice by increasing the expression of Sirtuin 3 (SIRT3), which activates mitochondrial autophagy. We also found that the liver may play a significant role in the pathogenesis of Alzheimer's disease (AD). However, it remains unclear whether HKL exerts its protection on AD through hepatic pathways.ObjectiveWe aimed to elucidate the impact of HKL on the liver of AD mice and its mechanisms.MethodsAPP/PS1 transgenic mice were utilized as AD models and administered with HKL and 3-TYP (an inhibitor of SIRT3). Congo-red staining and immunohistochemistry were conducted to detect the Aβ_1-42 plaque deposition in the brain. Hematoxylin-eosin and Oil red O staining were employed to observe alterations in hepatic morphology. Liver function markers were tested to assess the metabolic function. qRT-PCR was employed to examine the level of SIRT3 mRNA. Western blot was performed to evaluate the expression of SIRT3, insulin degrading enzyme (IDE), GpLD1, lipoprotein receptor related protein 1 (LRP-1), ANGPTL8, and superoxide dismutase 2 (SOD2).ResultsHKL mitigated the Aβ_1-42 plaque deposition in the brains of AD mice. It also reduced hepatic morphological damage. Additionally, HKL decreased the levels of ALT, AST, ALP, TBIL, and DBIL, and enhanced the levels of TP and ALB. It increased the levels of SIRT3 mRNA, and also the expression of SIRT3, IDE, GpLD1, and SOD2, while suppressing the expression of LRP-1 and ANGPTL8. 3-TYP could reverse all these effects of HKL on AD mice.ConclusionsHKL might alleviate liver damage of AD mice by upregulating SIRT3.