OBJECTIVETo study and establish the optimal technology for the preparation of evodiae juice.

METHODThe contents of evodiamine, rutaecarpine and evodin were simultaneously determined with HPLC, and each yield of the three compounds were chosen as the evaluating indicator. The orthogonal test coupled with the weighted coefficient method were adopted to acquire the optimal technology for the preparation of evodiae juice.

RESULTThe study showed that the optimal technology for the preparation of evodiae juice was as follows: decocted three times while the first time was with 12-fold of water socked 30 minutes and decocted 45 minutes, the second time was with 8-fold of water decocted 20 minutes and the third time was with 6-fold of water decocted 20 minutes.

CONCLUSIONThis method is simple and accurate. The optimal technology is suitable for industry manufacture of evodiae juice.

Drugs, Chinese Herbal ; analysis ; Evodia ; chemistry ; Technology, Pharmaceutical ; methods

AIMTo evaluate the similarity between two chromatographic fingerprints automatically with computer.

METHODSChromatogram can be treated as vector of hyperspace, and the similarity between them can be counted according to vectorial angle formula. This process was performed with software written in Visual Basic 6.0. The two main functions of this software are automatic peak tracking in two fingerprints under the same analytic condition and computing the similarity automatically.

RESULTSThe HPLC fingerprints of eleven kinds of Evodia rutaecarpa (Juss.) Benth (a traditional Chinese herb) from different sources were obtained and the similarities were calculated with this software. This method was shown to be a good way to evaluate the similarity between two fingerprints. A sample washed seven times with hot water can be clearly discriminated from other samples of Evodia rutaecarpa (Juss.) Benth with similar results.

CONCLUSIONThis method is a good way to evaluate the similarity between two fingerprints and is helpful in quality control of traditional Chinese medicine.

Evodia ; chemistry ; classification ; Plants, Medicinal ; chemistry ; Quality Control ; Software Design

Worldwide, caffeine is among the most commonly used stimulatory substances. Unfortunately, significant caffeine consumption is associated with several adverse effects, ranging from sleep disturbances (including insomnia) to cardiovascular problems. This study investigates whether treatment with the Evodia rutaecarpa aqueous extract (ERAE) from berries and its major molecular component, evodiamine, can reduce the adverse caffeine-induced sleep-related and excitation effects. We combined measurements from the pentobarbital-induced sleep test, the open field test, and the locomotor activity test in mice that had been dosed with caffeine. We found that ERAE and evodiamine administration reduced the degree of caffeine-induced sleep disruption during the sleep test. Additionally, we found that evodiamine significantly inhibits caffeine-induced excitation during the open field test, as well as decreasing hyperlocomotion in the locomotor activity test. Additional in vitro experiments showed that caffeine administration decreased the expression of γ-aminobutyric acid (GABA)(A) receptor subunits in the mouse hypothalamus. However, evodiamine treatment significantly reversed this expression reduction. Taken together, our results demonstrate that ERAE and its major compound, evodiamine, provide an excellent candidate for the treatment or prevention of caffeine-induced sleep disturbances and excitatory states, and that the mechanism of these beneficial effects acts, at least in part, through the GABA(A)-ergic system.
Animals ; Caffeine ; Evodia ; Fruit ; Hypothalamus ; In Vitro Techniques ; Mice* ; Motor Activity

Evodiamine, a bioactive indole alkaloid from Evodia rutaecarpa, E. rutaecarpa var. officinalis, or E. rutaecarpa var. bodinieri, has been extensively investigated due to its pharmacological activities in recent years. At present, evodiamine is proved to significantly suppress the proliferation of a variety of cancer cells and mediate cell processes such as cell cycle arrest and cell migration. In addition, evodiamine displays significant pharmacological activities against cardiovascular diseases(hyperlipidemia, etc.), and tinea manus and pedis. Recently, evodiamine has been found to have potential toxic effects, such as hepatotoxicity, nephrotoxicity, and cardiotoxicity. However, the pharmacological and toxicological mechanism of evodiamine is not clear, and its toxicity in vitro and in vivo has been rarely reported. Therefore, this study reviewed the pharmacological and toxicological articles of evodiamine in recent years, aiming at providing new ideas and references for future research.
Evodia ; Hand Dermatoses ; Humans ; Plant Extracts ; Quinazolines/toxicity* ; Tinea

OBJECTIVEDevelop an LC-MS method to determine evodiamine and rutaecarpine in rats plasma simultaneously. The method was employed to investigate pharmacokinetics of evodiamine and rutaecarpine.

METHODBlood samples were collected in different time after oral administrated with the extracts of Euodiae Fructus, the plasma concentration of evodiamine and rutaecarpine was determined by LC-MS, pharmacokinetic parameters were calculated by WinNonlin 5.1 software.

RESULTThe linear ranges of evodiamine and rutaecarpine were 0.5-100 microg x L(-1) (r = 0.995 9), 1-200 microg x L(-1) (r = 0.999 3) respectively. The average recovery were exceeded 76% (n = 5), the precision of inner-day and inter-day were less than 15%. The pharmacokinetics parameters AUC, t1/2, CL _F of evodiamine were: (2 215.24 +/- 414.49), (4 230.62 +/- 753.77), (13 219.21 +/- 3 740.95) min x ng(-1) x mL(-1); (146.57 +/- 38.38), (114.38 +/- 14.65), (163.37 +/- 8.83) min; (184 607.29 +/- 32 502.21), (192 878.22 +/- 31 897.37), (19 3224.63 +/- 62 278.74) mL x min(-1). The pharmacokinetics parameters AUC, t1/2, CL_F of rutaecarpine were (2 283.53 +/- 298.51), (4 424.84 +/- 276.95), (14 239.93 +/- 3648.27) min x ng(-1) x mL(-1); (167.10 +/- 15.82), (131.58 +/- 20.07), (144.41 +/- 13.65) min; (1 177 340.54 +/- 2 4942.21), (181 262.92 +/- 11 162.22), (177 508.10 +/- 52 611.80) mL x min(-1).

CONCLUSIONThe method described in this report has high sensitivity and selectivity, and was suitable for pharmacokinetic studies of evodiamine and rutaecarpine. The kinetic process of evodiamine and rutaecarpine in rats in vivo were all yielded to be one-compartment model.

Administration, Oral ; Animals ; Evodia ; Indole Alkaloids ; pharmacokinetics ; Male ; Plant Extracts ; pharmacokinetics ; Quinazolines ; pharmacokinetics ; Rats ; Rats, Wistar

OBJECTIVETo study the genetic background of Evodia rutaecarpa by AFLP, and analyze the genetic diversity of E. rutaecarpa from different areas.

METHODE. rutaecarpa genomic DNA was extracted. The AFLP reaction system was established and AFLP primer pairs were chosen for the analysis. Forty-six individuals of E. rutaecarpa which from five provinces were analyzed by AFLP. The NTSYS-pc 2.1 software was used for cluster analysis.

RESULTSix out of the original 72 pairs of primers were optimized for the study; AFLP analysis revealed the similarity coefficient of 0.53, the samples of E. rutaecarpa var. officinalis from Zhejiang province was separated from other accessions; E. rutaecarpa var. officinalis also showed more pronounced genetic variation than the E. rutaecarpa, and strong geo-related relevance.

CONCLUSIONVariance of genetic background of E. rutaecarpa are large, AFLP analysis method can obviously identify different varieties of E. rutaecarpa, and can detect the genetic characteristics of inter-regional differences.

Amplified Fragment Length Polymorphism Analysis ; DNA, Plant ; Evodia ; classification ; genetics ; Genetic Variation ; Phylogeny

OBJECTIVETo establish a HPLC fingerprint for quality evaluation of fructus Euodiae rutaecarpa, and to perform qualitative and quantitative analysis of its main constituents.

METHODThe 10 batches of samples were analyzed by HPLC linear gradient elution method and evaluated by similarity evaluation and system cluster analysis. The common peaks in chromatographic fingerprint were identified by LC-DAD-MS.

RESULTThe HPLC fingerprint of Euodiae Fructus showed 32 characteristic peaks, among them 13 peaks were identified, and 2 constituents were quantified.

CONCLUSIONThe HPLC fingerprint established could reflect the main constituents of Euodiae Fructus, and could combine with content determination to take an overall control of Euodiae Fructus.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Evodia ; chemistry

BACKGROUND: JES9501 is dehydroevodiamine, the extract of Evodia rutaecarpa, expected to be a new therapeutic for Alzheimer disease. This study aims to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of JES9501 after single or multiple dosing. METHODS: A double-blind, randomized, placebo-controlled, dose ascending, parallel study was conducted in healthy subjects. A single dose of JES9501 50.100.200.400 or 800 mg and multiple doses of JES9501 100.200 or 400 mg once-daily for 7days was administered. Serial blood and urine samples for PK evaluation were collected. Acetylcholinesterase (AChE) activity was measured for PD evaluation in multiple dose group. RESULTS: In the single dose study, means of dose-normalized peak concentration (Cmax) of 100.200.400 and 800 mg dose group are comparable except 50 mg dose group. Means of dose-normalized area under the plasma concentration-time curve (AUC) from dosing to the last quantifiable concentration of corresponding dose group were similar. At steady state in the multiple dose study, means of dose-normalized Cmax and AUC for dosing interval of 100.200 and 400 mg dose group decreased as the dose increased, however those were not relevant. There was no significant difference of AChE activity between three dosage groups and placebo group. Adverse events related to study drug were all mild and there were no remarkable findings. CONCLUSION: JES9501 was safe and well-tolerated after single or multiple doses in healthy male subjects. Further studies are warranted to evaluate the PK of optimized dosage form and to prove the drug effect in clinical trials for Alzheimer disease patients.
Acetylcholinesterase ; Administration, Oral* ; Alzheimer Disease ; Area Under Curve ; Dosage Forms ; Evodia ; Humans ; Male ; Pharmacokinetics* ; Plasma

This study is to develop a HPLC method for quality evaluation of Euodiae Fructus and related species by simultaneous determination limonin, indole alkaloids (14-fomyldihydroxyrutaecarpine, evodiamine, rutaecarpine), and quinolone alkaloids [1-methyl-2-undecyl-4 (1H)-quinolone, evocarpine, dihydroevocarpine] in the fruits of five Evodia species. Samples were analyzed on a YMC C18 column (4.6 mm x 250 mm, 5 microm) eluted with mobile phases of acetonitrile (A), tetrahydrofuran (B), and a buffer solution of 5 mmol x L(-1) ammonium acetate (pH 3.8) (C) in a linear gradient mode. The column temperature was 30 degrees C and the flow rate was 1.0 mL x min(-1). The PDA detector wavelengths were set at 220 and 250 nm. The seven compounds were well separated and showed good linearity (r = 0.999 9) within the concentration ranges tested. The mean recoveries were between 96.7%-102.4% (RSD 1.4%-3.1%). Through the validation, the method was proved to be accurate and repeatable. All the seven constituents were detected in the fruits of five species, but the contents of them varied widely in different samples. The total contents of seven constituents in 16 batches of Euodiae Fructus were 9.46-69.9 mg x g(-1), and the mean content was 28.2 mg x g(-1). The total content of seven constituents in E. compacta and E. fargesii was 25.8, 7.69 mg x g(-1), respectively.
Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; chemistry ; Evodia ; chemistry ; Fruit ; chemistry ; Time Factors

OBJECTIVETo study the constituents of Evodia rutaecarpa.

METHODThe constituents were isolated by various chromatographic techniques and the structures were elucidated by their physicochemical properties and the spectral data analysis.

RESULTEleven compounds were isolated and identified as rutaecarpine (1), dehydroevodiamine (2), limonin (3), wuchuyuamide I (4), evocarpine (5), daucosterol (6), taraxerone (7), 14-ursen-3-ol-1-one (8), trans-caffeic acid methylate (9), methyl coumarate (10), caffeine (11).

CONCLUSIONCompounds 7, 8, 10, 11 were isolated from E. rutaecarpa for the first time.

Evodia ; chemistry ; Magnetic Resonance Spectroscopy ; Organic Chemicals ; analysis ; isolation & purification ; Spectrometry, Mass, Electrospray Ionization