alpha-asarone and elemicin

Acorus tatarinowii Schott (AT), belong to the family Araceae, is perennial herbaceous plant mainly present in China, Japan and India. The rhizomes of AT have been used as a famous traditional Chinese medicine for the treatment of central nervous system related diseases.. A selective, accurate and sensitive method using gas chromatography-mass spectroscopy (GC-MS) for the simultaneous determination and pharmacokinetic study of β-asarone, α-asarone, elemicin and cis-methyl isoeugenol in rat plasma was developed and validated.. The GC-MS system was operated under selected ion monitoring (SIM) mode. The samples were prepared by protein precipitation with acetonitrile after being spiked with an internal standard (1-naphthol). The GC separation was achieved on a DB-1701 column (60 m × 0.25 mm ID, and 0.25 µm film thickness).. The current GC/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. The analyte calibration curves were linear over a wide concentration range and the lowest limit of quantifications (LLOQ) were 5.53 ng/mL (β-asarone), 6.50 ng/mL (α-asarone), 3.10 ng/mL (elemicin) and 7.60 ng/mL (cis-methyl isoeugenol). After oral administration 0.9 g /Kg of AT rhizomes, the maximum plasma concentration (Cmax) was 2508.6±498.7 ng/mL for β-asarone, 257.5±37.1 ng/mL for α -asarone, 345.5±33.4 ng/mL for elemicin and 452.7±59.1 ng/mL for cis-methyl isoeugenol, respectively. The time to reach the maximum plasma concentration (Tmax) was 1.42±0.18 h for β-asarone, 1.58±0.19 h for α -asarone, 1.67±0.24 h for elemicin and 1.75±0.38 h for cis-methyl isoeugenol, respectively.. This paper described a simple, sensitive and validated GC-MS method for simultaneous determination of four phenylpropanoids in rat plasma after oral administration of the essential oil of AT rhizomes and investigated on their pharmacokinetics studies as well.

Topics: Acorus; Administration, Oral; Allylbenzene Derivatives; Animals; Anisoles; Gas Chromatography-Mass Spectrometry; Male; Medicine, Chinese Traditional; Oils, Volatile; Pyrogallol; Rats; Rats, Wistar; Rhizome

To analyze the chemical components of the essential oil extracted from the seeds of Myristica fragrans (nutmeg) processed by different methods (steamed with water steam, roasted with flour, sauted with flour, roasted with talcum powder, roasted with loess, and roasted with bran) and to provide quality control foundations in the sciences.. The essential oil was extracted by steam distillation and separated with GC capillary column. The relative content of every compound was determined with area normalization method and the structures were elucidated by GC-MS technique.. Fifty-eight to one hundred and four of chromatographic peaks were detected, among them seventy-six compounds accounting for 98.32% to 99.99% of the total essential oil in nutmeg were identified, which were composed of 69.15% to 97.24% for monoterpenoids and 2.06% to 25.51% for aromatic compounds of the total essential oil, respectively.. It was shown that monoterpenoids and their derivatives were main composition, and aromatic compounds were secondary composition in the total essential oil of nutmeg grows in Indonesia and processed by different traditional methods on the basis of theory of traditional Chinese medicine. In addition, it was suggested that we should be careful to use processed nutmeg owing to contain safrole and a-asarone induced genetoxicity in animals and mutagenicity in the Ames Salmonella assay, and myristicin and elemicin induced narcotism in human. The processed method roasted with bran for nutmeg may be better and will be developed.

Topics: Allylbenzene Derivatives; Anisoles; Benzyl Compounds; Dioxolanes; Gas Chromatography-Mass Spectrometry; Hydrocarbons, Aromatic; Molecular Structure; Monoterpenes; Myristica; Oils, Volatile; Plant Oils; Plants, Medicinal; Pyrogallol; Reproducibility of Results; Safrole; Seeds; Technology, Pharmaceutical

Three allylbenzenes from Asiasarum heterotropoides, methyleugenol (1), elemicin (2) and gamma-asaron (3) showed suppressive effects on umu gene expression of the SOS response in the Salmonella typhimurium OY1001/1A2 umu test against the mutagen 2-amino-3,4-dimethylimidazo[4,5-f ]quinoline (MeIQ). Gene expression was suppressed 70.0, 75.9 and 81.7% at a concentration of 0.4 mM, respectively. The ID50 values (50% inhibition dose) of these compounds were 0.125, 0.098 and 0.059 mM, respectively. On the other hand, compounds 1-3 showed weak suppressive effects of the SOS-inducing activity on activated MeIQ.

Topics: Allylbenzene Derivatives; Anisoles; Antimutagenic Agents; Antineoplastic Agents; Aristolochiaceae; Eugenol; Mutagenicity Tests; Mutagens; Pyrogallol; Quinolines; SOS Response, Genetics

While the alkenylbenzenes alpha- and beta-asarone are hepatocarcinogenic in rodents, myristicin and elimicin, two other alkenylbenzenes, are not. The present study investigated the mechanism of genotoxicity of the asarones to elucidate the role of cytochrome P-450 and obtain further information about the relationships between the structure, metabolism and genotoxicity of the alkenylbenzenes. The data on the ability of these compounds to induce unscheduled DNA synthesis (UDS) in hepatocytes derived from male Fischer 344 rats are presented in this paper. Cytotoxicity was assessed by lactate dehydrogenase leakage. Elimicin and alpha- and beta-asarone are genotoxic in the UDS assay but myristicin is not. The genotoxicity of the asarones is inhibited by the cytochrome P-450 inhibitor cimetidine but the sulfotransferase inhibitor pentachlorophenol (PCP) is without effect. The major metabolite of the asarones in hepatocytes was identified by liquid chromatography-mass spectrometry as 2,4,5-trimethoxycinnamic acid but this was not genotoxic when tested separately. Simple allylbenzenes such as safrole, estragole and methyleugenol are activated by sequential 1-hydroxylation and sulfation, and this is the likely mechanism of the genotoxicity of elimicin. The propenyl analogues isosafrole, anethole and methylisoeugenol, which cannot undergo 1-hydroxylation, are not genotoxic. The positive results obtained with the asarones suggest the occurrence of a novel activation 'option' for alkenylbenzenes which features a 2-methoxy group in the aromatic ring.

Topics: Alkylation; Allylbenzene Derivatives; Animals; Anisoles; Benzyl Compounds; Biotransformation; Cells, Cultured; Cimetidine; Dioxolanes; DNA; DNA Damage; DNA Repair; L-Lactate Dehydrogenase; Liver; Male; Pentachlorophenol; Pyrogallol; Rats; Rats, Inbred F344; Structure-Activity Relationship