Activities of hepatic cytosol enzymes involved in UDP-g1ucuronic acid synthesis as well as in glutathione reduction and conjugation systems were determined following administrations of butylated hydroxyanisole (approximately 5 mmol/kg body weight/day) and of equimolar intake doses of its structural anglogs. These compounds included the multi-functional group side chain compounds (t-butyl hydroquinone, 4-hydroxy- anisole, hydroquinone, benzoquinone) and the mono-functional side chain compounds (t-butyl benzene, anisole, phenol). They were administered to mice for 10 days either by mixing them in the diet or by oral intubations. Results showed that glutathione Stransferase activities were markedly increased by all tested compounds except for the t-butyl benzene. Activities of glutathione reductase and glucose 6-phosphate dehydrogenase were increased together on1y by BHA and t-butyl hydroguinone. UDP-glucose dehydrogenase and NADH:quinone reductase activities were significantly elevated by the multi-functional side chain compounds, but not by the mono-functional analogs. The relations between chemical structures of tested BHA analogs and elevations of the measured hepatic cytosol conjugation (detoxification) system enzyme activities for the metabolism and excretion of BHA analogs are discussed.
Animal ; Anisoles/metabolism* ; Butylated Hydroxyanisole/analogs & derivatives ; Butylated Hydroxyanisole/metabolism* ; Cytosol/enzymology* ; Glutathione/metabolism* ; Mice ; Uridine Diphosphate Glucuronic Acid/biosynthesis* ; Uridine Diphosphate Sugars/biosynthesis*

Effects of feeding 2(3)-tert-butyl 4-hydroxyanisole (BHA) and 3, 5-di-tert-butyl 4-hydroxytoluene (BHT) on the rates of mixed function oxidation and conjugation enzyme reactions have been determined using isolated hepatic microsomal fractions and isolated perfused livers of mice. The treatments with either of the antioxidants have increased the rates of O-demethylation for p-nitroanisole and of O-deethylation for 7-ethoxycoumarin up to 2-fold, both in microsomes and in perfused liver. Analysis of the perfusate showed that the increased amounts of p-nitrophenol and 7-hydroxycoumarin produced by the elevated mixed-function oxidase activities were reflected by the increase in the amounts of glucuronide conjugates and not in the increase for the amounts of the sulfate ester conjugates. Comparison of results also indicated that in the perfused liver, the maximal rate of metabolite conjugation is limited by the maximal rates of the initial mixed function oxidase activities.
Alkylation ; Animal ; Anisoles/metabolism ; Anisoles/pharmacology* ; Butylated Hydroxyanisole/administration & dosage ; Butylated Hydroxyanisole/pharmacology* ; Butylated Hydroxytoluene/administration & dosage ; Butylated Hydroxytoluene/analogs & derivatives* ; Butylated Hydroxytoluene/pharmacology ; Comparative Study ; Coumarins/metabolism ; Female ; Glucuronosyltransferase/metabolism ; Liver/metabolism* ; Mice ; Microsomes, Liver/enzymology ; Microsomes, Liver/metabolism* ; Mixed Function Oxygenases/metabolism ; Oxidation-Reduction ; Perfusion ; Support, U.S. Gov't, P.H.S.

OBJECTIVETo study the liposoluble ingredients of Quchiling (LQ), which enter the blood and the brain,and to confirm the active ingredients of LQ in vivo.

METHODSerum pharmacochemistry and gas chromatography mass spectroscopy were used to analyze ingredients of LQ entering the blood and the brain.

RESULTThere were eleven ingredients of LQ to enter the blood and six ingredients of LQ to enter the brain.

CONCLUSIONIt is confirmed that eleven ingredients of LQ entered the blood, which are beta-asarone, schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B, schisantherrin A, schisantherrin B, schisantherrin C, delta-cadinene, delta-cadinol and calamendiol in the blood, and that six ingredients are beta-asarone, schisandrol A, schisandrol B, deoxyschisandrin, schisandrin B and calamendiol in the brain.

Animals ; Anisoles ; chemistry ; metabolism ; Brain ; metabolism ; Cyclooctanes ; chemistry ; metabolism ; Dioxoles ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; metabolism ; pharmacokinetics ; Female ; Gas Chromatography-Mass Spectrometry ; Lignans ; chemistry ; metabolism ; Male ; Polycyclic Compounds ; chemistry ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of beta-asarone on expression of immediately early gene c-fos in kindling epilepsy rat brain.

METHODThe rats were randomly divided in to beta-asarone groups (200, 100, 50 mg x kg(-1) x d(-1)), difetoin control group (36 mg x kg(-1)) and model group. The remedy was administered orally. The effects were observed in kindling epilepsy model induced by penicillin, then the expression of c-fos were determined by western blot (hippocampus) and immunohistochemical techniques (cortex).

RESULTBeta-asarone could significantly increase the expression of c-fos in kindling epilepsy rat brain, and show its quantity-effect relation. The expression of c-fos in hippocampus was (1139.45 +/- 155.56), (1109.56 +/- 134.03), (1103.73 +/- 235.82) CNT x mm2 in beta-asarone groups, 920.54 +/- 203.20 in model control group, and 1106.26 +/- 186.24 in difetoin group, respectively. The number of c-fos positive cell was 87.1 +/- 2.2, 76.3 +/- 1.3 and 59.9 +/- 1.3 in beta-asarone groups, 39.3 +/- 2.6 in model control group, and 95.2 +/- 1.1 in difetoin group, respectively.

CONCLUSIONBeta-asarone can obviously increase the expression of c-fos in epilepsy rat brain. It is one of important response to epilepsy.

Animals ; Anisoles ; pharmacology ; Blotting, Western ; Brain ; drug effects ; metabolism ; Epilepsy ; drug therapy ; metabolism ; Female ; Gene Expression ; drug effects ; Immunohistochemistry ; Male ; Proto-Oncogene Proteins c-fos ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

An experiment was conducted in order to investigate the effect of p-dimethylaminoazobenzene (DAB) and 2(3)-tert-butyl-4-hydroxyanisole (BHA) on the lipid peroxidation and peroxide-destroying enzyme system in the rat liver. Dietary supplementation of DAB (0.06%) for three weeks caused the elevation of glutathione-S-transferase activity by 60% and glutathione reductase by 50%, but it decreased glutathione peroxidase and catalase activities significantly. Dietary supplementation of BHA (0.75%) also increased glutatione-S-transferase activity in the liver by 2 folds, and it counteracts DAB effect on the glutathione peroxidase and catalase activities. There was a marked increase in malon-dialdehyde content in the postnuclear fraction of liver by the treatment of DAB, but the addition of BHA lowered the malondialdehyde content to almost the control level. The protective effect of BHA on the lipid peroxidation induced by DAB administration at the enzyme level seems to be due to the induction of glutathione-S-transferase and the protection of glutathione peroxidase and catalase activities from being lowered by DAB administration.
Animal ; Anisoles/pharmacology* ; Butylated Hydroxyanisole/pharmacology* ; Glutathione Peroxidase/analysis* ; Glutathione Reductase/analysis* ; Glutathione Transferase/analysis* ; Lipid Peroxides/metabolism* ; Liver/drug effects* ; Liver/metabolism ; Male ; Peroxidases/analysis* ; Rats ; p-Dimethylaminoazobenzene/pharmacology*

A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.
Acetylcholinesterase ; metabolism ; Anisoles ; chemical synthesis ; chemistry ; pharmacology ; Binding Sites ; Butyrylcholinesterase ; metabolism ; Catalytic Domain ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Inhibitory Concentration 50 ; Tacrine ; chemical synthesis ; chemistry ; pharmacology

AIMTo study the pharmacokinetics of beta-asarone in rats.

METHODSThe concentration of beta-asarone in serum and organs were measured by HPLC after i.g. administration, the pharmacokinetics was analyzed with DAS software regarding the organs as independent system.

RESULTSThe pharmacokinetics of beta-asarone can be described as first order process of one-compartment model. In the serum, T(1/2), Tpeak and Cmax were 54 min, 12 min and 3.19 mg x L(-1), respectively. The procedure in the organs was similar to that in serum.

CONCLUSIONThe absorption, distribution and elimination of beta-asarone are very rapid, and it is easy to pass through blood brain barrier. Brain is an important organ of distributing of beta-asarone.

Acorus ; chemistry ; Administration, Oral ; Animals ; Anisoles ; administration & dosage ; isolation & purification ; pharmacokinetics ; Area Under Curve ; Blood-Brain Barrier ; Brain ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Female ; Half-Life ; Male ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

OBJECTIVETo study the effects of Annao tablet (main component is beta-asarone) on S100B and NPY of cortex in chronic epilepsy rats.

METHODThe remedy was administered orally. The effects were observed in convulsion model induced by PG, then S100B protein and NPY of cortex were determined.

RESULTAnnao tablet could depress the epileptic degree, postpone spasm latent period and reduce the wet dog sample (WDS) times. The remedy could decline S100B and NPY of cortex in chronic epilepsy rats.

CONCLUSIONAnnao tablet has obvious antiepileptic effects and can reduce the nerve cell damage induced by epilepsy.

Acorus ; chemistry ; Animals ; Anisoles ; administration & dosage ; isolation & purification ; pharmacology ; Anticonvulsants ; administration & dosage ; isolation & purification ; pharmacology ; Cerebral Cortex ; metabolism ; Drug Carriers ; Epilepsy ; metabolism ; physiopathology ; Female ; Male ; Neuropeptide Y ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; S100 Proteins ; metabolism ; Tablets ; beta-Cyclodextrins

OBJECTIVETo prepare the alpha-asarone reservoir patch and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug's permeation rate.

METHODThe alpha-asarone reservoir patch was prepared using 1% hydroxypropyl methylcellulose (HPMC) of ethanol solution as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and several permeation enhancers were evaluated. High performance liquid chromatorgraphy (HPLC) was used to determine alpha-asarone's content and permeation rate.

RESULTThe release mechanisms of alpha K-asarone patch in vitro coincided with zero-order kinetic. 30% ethanol cooperates with 1% Isopropyl Myristate (IPM) have the best effect on permeation of the patch. The permeation rate reaches (20.67 +/- 1.33) microg x cm(-2) h(-1).

CONCLUSIONEthanol combined with IPM is good permeation enhancer, which facilitated the permeation of alpha K-asarone to fit the clinical requirements. However, the further studies of the skin's stimulation and bioavailability are needed.

Acorus ; chemistry ; Administration, Cutaneous ; Anisoles ; administration & dosage ; isolation & purification ; pharmacokinetics ; Delayed-Action Preparations ; administration & dosage ; pharmacokinetics ; Ethanol ; pharmacology ; Humans ; Hypromellose Derivatives ; In Vitro Techniques ; Methylcellulose ; analogs & derivatives ; chemistry ; Myristates ; pharmacology ; Plants, Medicinal ; chemistry ; Polyvinyls ; chemistry ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects