Abstract
Leaves from Eugenia uniflora, the red Brazilian cherry, have a high content of flavonoids that possess several biological effects such as anti-inflammatory, antioxidant, and antidiabetic activities. However, their influence on carbon tetrachloride (CCl4)-induced acute liver injury in rats has not been investigated. In the current study, a bioguided fractionation assay revealed that the ethyl acetate fraction (EAF) of Eugenia uniflora is the safest and most active fraction. LC-MS analysis of the ethyl acetate fraction revealed 22 secondary metabolites, mainly myricetin and quercetin derivatives. EAF did not show toxicity up to 2000 mg/kg, and exhibited antioxidant activities in vitro in DPPH assay with IC50 of 3.35 µg/mL. Additionally, EAF exhibited substantial antioxidant activities in vivo by counteracting the oxidative damage of the prooxidant juglone [80 µM] in Caenorhabditis elegans model organism and increased its survival rate in a dose-dependent fashion through the DAF-16/Foxo pathway. Furthermore, the hepatoprotective activity of EAF (200 mg/kg against carbon tetrachloride (CCl4) intoxicated male Wistar rats was assessed. EAF significantly inhibited CCl4-induced elevation of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TB), total cholesterol (TC), and triglycerides (TG), in the blood serum and prevented lipid peroxidation and restored superoxide dismutase (SOD) activity and glutathione (GSH) content in liver tissues. The observed hepatoprotective effects of EAF, which were supported by histopathological observations as pretreatment with EAF, effectively attenuated the CCl4-induced histopathological changes. In conclusion, EAF of Eugenia uniflora leaves has substantial hepatoprotective activities against CCl4 induced acute liver injury in rats due to its antioxidant activity.
Highlights
The liver is the main organ responsible for performing diverse pivotal metabolic functions
The aim of this study was to investigate the antioxidant and hepatoprotective potential of a polyphenol rich fraction from E. uniflora leaves in vivo models and its antioxidant activities in vitro
EAF exhibited the highest activities in the DPPH assay and increased the survival rate in C. elegans via inducing nuclear localization of DAF-16::GFP, indicating that the in vivo antioxidant effect could involve the DAF-16/FOXO signalling pathway
Summary
The liver is the main organ responsible for performing diverse pivotal metabolic functions It plays a major role in carbohydrate, lipid, and protein metabolism. It acts as a storage site for glycogen; vitamins A, D, and B12; and iron. It synthesizes 90% of the plasma proteins, and produces the bile [1,2]. Venous blood emerging out of the intestine passes first to the liver through the hepatic portal vein before reaching the systemic circulation [1] This implies that the hepatocytes are exposed to all toxins and harmful substances taken orally. Oxidative stress is involved in the pathogenesis of inflammation, cell death, neurodegenerative diseases, and cancer [4,5]
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