title: 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 (O(2)·-), hydroxyl (·OH), nitric oxide (·NO) and lipid peroxide (LOO·) - physiologically relevant free radicals with IC(50) 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 CuSO(4)-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.
authors.affiliation: Department of Food Protectants and Infestation Control, Central Food Technological Research Institute, Mysore, Karnataka, India
authors.forename: Anup
authors.initials: A
authors.lastname: Srivastava
authors.forename: L
authors.initials: L
authors.lastname: Jagan Mohan Rao
authors.forename: T
authors.initials: T
authors.lastname: Shivanandappa
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor; D045744:Cell Line, Tumor / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000032:analysis; D008099:Liver / Q000187:drug effects; D008297:Male; D008515:Medicine, Ayurvedic; D051379:Mice; D015394:Molecular Structure; D016877:Oxidants / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D015262:Xenobiotics / Q000633:toxicity
chemical_list: C571833:2,4,8-trihydroxybicyclo(3.2.1)octan-3-one; D001643:Bridged Bicyclo Compounds; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D008077:Lipoproteins, LDL; D016877:Oxidants; D015262:Xenobiotics; C099252:oxidized low density lipoprotein; D013481:Superoxides; D017665:Hydroxyl Radical