Antioxidant Activity of Bakuchiol: Experimental Evidences and Theoretical Treatments on the Possible Involvement of the Terpenoid Chain

The protective activity of the plant-derived meroterpene, bakuchiol [1-(4-hydroxyphenyl)-3,7-dimethyl-3-vinyl-1,6-octadiene, 1], against oxidative damages to lipids and proteins has been investigated and rationalized based on the scavenging activity of 1 against various oxidizing radicals (Cl3CO2•, linoleic acid peroxyl radicals, LOO•, DPPH radicals, •OH, and glutathiyl radicals). The rate constants of the scavenging reactions, transients formed in these reactions, and their mechanistic pathways have been probed using optical pulse radiolysis technique. Besides 1, its methyl ether derivative 2 also could prevent lipid peroxidation in rat brain homogenate, indicating the probable participation of their terpenoid chains in scavenging LOO•. This was further corroborated from the pulse radiolytic studies on the reaction between the glutathiyl radicals and the compounds 1 and 2 as well as two other congeners, 3 and 4, which showed transient absorptions at ∼300 nm attributable to some C-centered allylic radicals. On the basis of the strong signals at ∼300 nm with 1−3 as compared to compound 4, formation of the allylic radical adjacent to the trisubstituted olefin function in 1−3 was envisaged. This was confirmed by quantum chemical calculations of the relative energies of the probable radical species derivable from 2 using Hartree−Fock and density functional theory along with self-consistent reaction field model. In the case of 1, the allylic radical was found to be transformed into the phenoxyl radical at a later stage. All of these data revealed, for the first time, the importance of the terpenoid moiety of bakuchiol in controlling its antioxidant action via radical scavenging.