2,4,8-trihydroxybicyclo [3.2.1]octan-3-one scavenges free radicals and protects against xenobiotic-induced cytotoxicity

Abstract

Currently, there is a great deal of interest in the study of natural compounds with free-radical-scavenging activity because of their potential role in maintaining human health and preventing diseases. In this paper, we report the antioxidant and cytoprotective properties of 2,4,8-trihydroxybicyclo [3.2.1]octan-3-one (TBO) isolated from the aqueous extract of Decalepis hamiltonii roots. Our results show that TBO is a potent scavenger of superoxide (O2·−), hydroxyl (·OH), nitric oxide (·NO) and lipid peroxide (LOO·) – physiologically relevant free radicals with IC50 values in nmolar (42–281) range. TBO also exhibited concentration-dependent secondary antioxidant activities such as reducing power, metal-chelating activity and inhibition of protein carbonylation. Further, TBO at nmolar concentration prevented CuSO4-induced human LDL oxidation. Apart from the in vitro free-radical-scavenging activity, TBO demonstrated cytoprotective activity in primary hepatocytes and Ehrlich ascites tumour (EAT) cells against oxidative-stress-inducing xenobiotics. The mechanism of cytoprotective action involved maintaining the intracellular glutathione (GSH), scavenging of reactive oxygen species (ROS) and inhibiting lipid peroxidation (LPO). Based on the results, it is suggested that TBO is a novel bioactive molecule with implications in both prevention and amelioration of diseases involving oxidative stress as well as in the general well-being.