Title:Hepatoprotective Effect of Myricetin following Lipopolysaccharide/DGalactosamine:
Involvement of Autophagy and Sirtuin 1
Volume: 16
Author(s): Amir Rostami, Tourandokht Baluchnejadmojarad and Mehrdad Roghani*
Affiliation:
- Neurophysiology Research Center, Shahed University, Tehran, Iran
Keywords:
Liver injury, myricetin, lipopolysaccharide, inflammation, oxidative stress, autophagy.
Abstract:
Background: Acute liver injury (ALI) is a critical and fatal disorder associated with excessive
oxidative stress and inflammation, ultimately leading to the death of hepatocytes. Myricetin is a
bioflavonoid in some berries, including blueberries and strawberries, with anti-inflammatory, antioxidant
and anti-apoptotic properties.
Objective: In the current research, the hepatoprotective potential of myricetin was studied in the
LPS/D-GalN model of ALI in C57BL/6 mice.
Methods: For inducing liver injury, D-GalN (400 mg/kg) and LPS (50 µg/kg) were injected via intraperitoneal
route and myricetin was orally administered (25 or 100 mg/kg/day) for two days before inducing
injury. Functional indices of liver dysfunction along with hepatic apoptotic, autophagic, oxidative
stress and inflammatory factors were measured.
Results: Myricetin (100 mg/kg) reduced the fatality rate of animals and pathological liver changes and
suitably lowered serum levels of total bilirubin, 8-OH-dG, ALT, AST and ALP in addition to decreasing
apoptotic, oxidative and inflammatory factors, NOX, NLRP3, caspase 3, MPO and enhancing
some antioxidants. Besides, myricetin improved the hepatic level and activity of sirtuin 1 and reversed
inappropriate alterations of autophagic parameters, including LC3 II, Beclin 1, and P62. The beneficial
effects of myricetin were attenuated after co-treatment with the autophagy inhibitor 3-
methyladenine.
Conclusion: This study indicates the hepatoprotective potential of myricetin that can be ascribed to its
down-regulation of oxidative, apoptotic, and inflammatory factors and upregulation of antioxidants
besides its partial regulation of sirtuin 1 and autophagic pathway.