Hepatoprotective Effect of Myricetin following Lipopolysaccharide/DGalactosamine: Involvement of Autophagy and Sirtuin 1

Abstract

Background: Acute liver injury (ALI) is a critical and fatal disorder which is associated with excessive oxida¬tive stress and inflammation and ultimate 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, hepatoprotective potential of myricetin was studied in LPS/D-GalN model of ALI in C57BL/6 mice. Methods: For inducing liver injury, D-GalN (400 mg/kg) and LPS (50 g/kg) was injected via intraperitoneal route and myricetin was orally administered (25 or 100 mg/kg/day), from two days till 1 h 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 lethality rate of animals and liver pathological 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 hepatic level and activity of sirtuin 1 and reversed inappropriate alterations of autophagic parameters including LC3 II, Beclin 1 and P62. Beneficial effects of myricetin was attenuated after co-treatment with the autophagy inhibitor 3-methyladenine. Conclusion: This study indicates 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.

Sirtuins as Players in the Signal Transduction of Citrus Flavonoids

“…Along this line, considering that one of the most validated methods to evaluate liver and kidney damage is the employment of lipopolysaccharides (LPSs), Rostami and collaborators demonstrated through this method the modulatory effect of MYR on SIRT1. Indeed, MYR reduced the serum levels of hepatic parameters, as well as the oxidative and inflammatory factors, through a mechanism characterized by the upregulation of hepatic SIRT1 [117]. Similarly, endotoxemic kidney injury was mitigated by RU in C57BL/6 mice by suppressing both oxidative and inflammatory processes via the activation of SIRT1 [118].…”

Myricetin as a Promising Flavonoid with Multitargeted Biological Activity

“…Кроме того, флавоноид улучшает уровень и активность сиртуина 1 в печени и способствует обратному развитию неблагоприятиых изменений параметров аутофагии, включая LC3 II, беклин 1 и P62. При этом положительный терапевтический эффект М ослабевает в случае совместного его применения с ингибитором аутофагии -3-метиладенином [71]. Флавоноид проявляет защитную роль против индуцированного липополисахаридами и D-галактозамином молниеносного гепатита у мышей путём подавления апоптоза клеток печени, воспаления и окислительного стресса.…”

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

“…Myricetin was found to alleviate liver injury by modulating sirtuin 1 signaling and restraining autophagy, in addition to inhibiting inflammation and oxidative stress (Guo et al, 2015;Rostami et al, 2023).…”

“…Myricetin was found to alleviate liver injury by modulating sirtuin 1 signaling and restraining autophagy, in addition to inhibiting inflammation and oxidative stress (Guo et al, 2015; Rostami et al, 2023). Moreover, myricetin suppressed CCl 4 ‐induced liver fibrosis through suppressing α‐SMA and collagen type I deposition and blocking TGF‐β1‐induced HSC activation (Geng et al, 2017).…”