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.

Keywords::

• 2,4,8-trihydroxybicyclo [3.2.1]octan-3-one
• Decalepis hamiltonii
• antioxidant
• ROS
• lipid peroxidation
• glutathione

Acknowledgement

This work was done at Central Food Technological Research Institute, Mysore, India. The authors wish to thank the Director of the institute for his keen interest in this study. The first author acknowledges Council for Scientific and Industrial Research, New Delhi, for awarding the research fellowship.

Declaration of interestAuthors declare no conflicts of interest.

This paper was first published online on Early Online on 30 January 2012.