Protection of the flavonoid fraction from Rosa laevigata Michx fruit against carbon tetrachloride-induced acute liver injury in mice

Protective effect of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice was investigated. Pretreatment with TFs significantly decreased CCl4-induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT) activities as well as the relative liver weight. Histopathological observation also revealed that TFs reduced the incidence of liver lesions and improved hepatocyte abnormality. Moreover, oral administration of TFs significantly enhanced antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase), increased the content of glutathione and decreased the content of malondialdehyde. Further research indicated that TFs prevented the DNA fragmentation and mitochondrial ultrastructural alterations caused by CCl4 based on TUNEL and transmission electron microscopy (TEM) assays. Moreover, pretreatment with TFs down-regulated the protein expressions of CYP2E1, iNOS, NF-κB, Bak and Caspase-3. Quantitative Real-time PCR assay suggested that TFs markedly decreased the levels of TNF-α, Fas/FasL and Bax gene expressions, and increased the level of Bcl-2. This is the first time to report the significant hepatoprotective effect of TFs from R. laevigata Michx fruit against CCl4-induced liver injury in mice and the action should be through reducing oxidative stress and suppressing inflammation and apoptosis.