Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol

Ethnopharmacological relevance: Zingiber officinale Rosc. (Zingiberaceae) has been traditionally used in Ayurvedic, Chinese and Tibb-Unani herbal medicines for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. Although gingerols and shogaols are the major bioactive compounds present in Zingiber officinale, their molecular mechanisms of actions and the relationship between their structural features and the activity have not been well studied. Aim of the study: The aim of the present study was to examine and compare the antioxidant and anti-inflammatory activities of gingerols and their natural analogues to determine their structure-activity relationship and molecular mechanisms. Materials and methods: The in vitro activities of the compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol were evaluated for scavenging of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibition of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), inhibition of lipopolysaccharide induced nitrite and prostaglandin E-2 production in RAW 264.7 cells. Results: In the antioxidant activity assay, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaot exhibited substantial scavenging activities with IC50 values of 26.3, 19.47, 10.47 and 8.05 mu M against DPPH radical, IC50 values of 4.05, 2.5,1.68 and 0.85 mu M against superoxide radical and IC50 values of 4.62, 1.97, 1.35 and 0.72 mu M against hydroxyl radical, respectively. The free radical scavenging activity of these compounds also enhanced with increasing concentration (P < 0.05). On the other hand, all the compounds at a concentration of 6 mu M have significantly inhibited (P < 0.05) f-MLP-stimulated oxidative burst in PMN. In addition, production of inflammatory mediators (NO and PGE(2)) has been inhibited significantly (P < 0.05) and dose-dependently. Conclusions: 6-Shogaol has exhibited the most potent antioxidant and anti-inflammatory properties which can be attributed to the presence of alpha,beta-unsaturated ketone moiety. The carbon chain length has also played a significant role in making 10-gingerol as the most potent among all the gingerols. This study justifies the use of dry ginger in traditional systems of medicine. (C) 2009 Elsevier Ireland Ltd. All rights reserved.