ABSTRACT
Bakuchiol, extracted from the plant Psoralea corylifolia, has been proven to have anti-tumor, cytotoxic, anti-microbial and anti-inflammatory activity. In order to study if radiolabeled bakuchiol exhibits enhanced cytotoxicity, bakuchiol was radiolabeled with 125I. In-vitro uptake studies of 125I-bakuchiol were carried out using LS-A (lymphosarcoma) and barcl-95 (radiation-induced thymic lymphoma) ascitic and solid tumor cells of murine origin. In both LS-A and barcl-95, 125I-bakuchiol showed significant uptake. Viability studies showed that the radioiodinated compound showed greater cytotoxic effect than bakuchiol.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Iodine Radioisotopes/pharmacology , Phenols/pharmacology , Radiopharmaceuticals/pharmacology , Animals , Antineoplastic Agents, Phytogenic/pharmacokinetics , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Iodine Radioisotopes/pharmacokinetics , Isotope Labeling , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/radiotherapy , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/radiotherapy , Mice , Phenols/pharmacokinetics , Plant Extracts/metabolism , Psoralea/chemistry , Radiopharmaceuticals/pharmacokineticsABSTRACT
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 (Cl(3)CO(2)(*), 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 approximately 300 nm attributable to some C-centered allylic radicals. On the basis of the strong signals at approximately 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.
Subject(s)
Antioxidants/pharmacology , Psoralea , Seeds/chemistry , Terpenes/pharmacology , Animals , Antioxidants/chemistry , Biphenyl Compounds , Brain/drug effects , Brain/metabolism , Brain Chemistry/drug effects , Calorimetry , Drugs, Chinese Herbal , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Free Radicals/antagonists & inhibitors , Free Radicals/chemical synthesis , Linoleic Acids/antagonists & inhibitors , Linoleic Acids/chemistry , Linoleic Acids/metabolism , Lipid Peroxidation/drug effects , Phenols/chemistry , Phenols/isolation & purification , Phenols/metabolism , Phenols/pharmacology , Picrates/chemistry , Proteins/drug effects , Proteins/metabolism , Pulse Radiolysis , Rats , Rats, Wistar , Terpenes/chemistry , Terpenes/metabolismABSTRACT
Significant incorporations of labelled leucine, valine and isovaleric acid into the meroterpene, bakuchiol (1) isolated from the medicinal plant, Psoralea corylifolia have been observed. Degradation experiments show that labels from these substrates find their way into both phenylpropane derived as well as terpenic part of 1 thereby indicating that none of the known pathways is operative in the case of 1. It is suggested that these substrates are metabolised to CO2 which is then incorporated into 1.
Subject(s)
Fabaceae/metabolism , Leucine/metabolism , Phenols/metabolism , Plants, MedicinalABSTRACT
Diallyl disulphide (DADS) is a major constituent of garlic oil. Uptake of [35S]-labelled diallyl disulphide by mouse liver is highest at 90 min after treatment with [35S]-DADS, 70% of the radioactivity is present in the liver cytosol of which 80% is metabolized to sulphate.