In vivo and in silico investigations of flavonoids from Rhamnus alaternus L. in mitigating ethanol-induced oxidative stress and inflammation

Abstract

To investigate the protective effects of Rhamnus alaternus L. against ethanol-induced toxicity, female Wistar rats were divided into 3 groups of 8 rats: control, ethanol (4 g/kg - 40 %), and ethanol with total oligomer flavonoids (TOF) (5 mg/kg). Various parameters, including biochemical and oxidative stress markers, histopathological damage, reactive oxygen species (ROS), nitric oxide (NO) and lysosomal activity in peritoneal macrophages, and cytokine levels, were evaluated after 4 weeks of treatment. Our study demonstrated that ethanol induced a considerable disruption of hematological indices, an increased level of biochemical markers, and MDA level with decreased antioxidant enzyme activities. Furthermore, an increase in ROS, NO levels, lysosomal activity and a significant increase in cytokines levels, indicated inflammation. TOF, however, restored normal levels of hematological indices, biochemical, antioxidant enzymes, and cytokines, and improved histological anomalies. TOF was found to protect rats from ethanol-induced damage owing to its antioxidant and anti-inflammatory properties. In addition, molecular docking simulations of the identified phytocompounds against ‘superoxide dismutase (pdb:4A7G)’ and ‘glutathione peroxidase 1 (pdb:2F8A)’ were performed. Significant results are obtained especially with ‘Kaempferol-3-O-rutinoside’.