Research Progress of Herb Pair Rhizoma Coptidis-Fructus Evodiae

The herb pair is the basic form of compatibility and application of traditional Chinese medicine.Herb pairs have the advantages of simple structure,clear compatibility and effective characteristics,and are suitable for scientific research.Rhizoma Coptidis-Fructus Evodiae is a relatively fixed combination of two herbs commonly used in clinical Chinese medicine.Chinese medicine uses it to treat various diseases caused by damp-heat accumulation in the liver and gallbladder,and spleen and stomach.The two medicines in the herb pair are opposite in nature but complement each other,and can achieve a great effect based on simple combination.Modern research shows that the herb pair has a wide range of pharmacological effects and good anti-tumor,analgesic,bacteriostatic and anti-inflammatory activity,and show good curative effects on stress ulcers,functional dyspepsia,chronic colitis,etc.This paper reviewed the research progress on the herb pair of Rhizoma Coptidis-Fructus Evodiae.

An Improved Method of Simultaneous Determination of Four Bioactive Compounds in Evodiae Fructus Using Ionic Liquids as Mobile Phase Additives in High Performance Liquid Chromatography

There are many compounds with different structures and chemical properties in Evodiae Fructus. It is hard to simultaneously determine the bioactive compounds by high performance liquid chromatography（HPLC）. A new method was proposed for four bioactive compounds（synephrine, limonoids, evodiamine and rutecarpine） to be separated completely and determined accurately using ionic liquids（ILs） as mobile phase additives. The mechanism and the effect of the ILs for changing the chromatographic behaviors of the four compounds were studied by systemati- cally changing the pH value of mobile phase, the types and concentrations of ILs as well as the concentrations of phosphate buffer. The chromatographic behaviors of the analytes with a mobile phase containing ILs complied with the stoichiometric displacement model for retention（SDM-R）. All results demonstrate the dual nature of ionic liquids, which are competitive adsorption and ion-pair agent. Meanwhile, excellent linearity was observed for all the com- pounds with correlation coefficients between 0.9992 and 0.9998. The limit of detection and the limit of quantification of the four compounds varied from 0.47μg/mL to 0.87 μg/mL and from 1.79 μg/mL to 2.44μg/mL, respectively. Three kinds of Evodiae Fructus processed through different methods were analyzed via the method. The result shows that the contents of evodiamine and rutecarpine as the two main active compounds by processing with vinegar and salt are obviously higher than those of the raw products.

Variations in the Composition of Fructus Evodiae after Processing with Radix Glycyrrhizae Extract

Objective： To evaluate the changes in the concentrations of five components in Fructus Evodiae used in Chinese medicine, including evodiamine and glycyrrhizic acid, during processing of Fructus Evodiae with Radix Glycyrrhizae extract by using high performance liquid chromatography （HPLC） and to provide a scientific basis for different clinical uses of processed and unprocessed Fructus Evodiae. Methods： The concentrations of the Fructus Evodiae components in processed or unprocessed Fructus Evodiae were evaluated by HPLC using a YMC J＇sphere ODS-H80 column （4.6 mm × 250 ram, 5 μm） with acetonitrile-water-tetrehydrofuran-acetic acid （41：59：1：0.2, v/v/v/v） as the mobile phase. The detection wavelength was 225 nm, the column temperature was 35 %, the flow rate was 1.0 mL/min, and the injection volume was 10 μL. The concentrations of the Radix Glycyrrhizae components were determined by HPLC with a KromasiI-C18 column （4.6 mm × 250 mm, 4 μm） and a gradient elution of acetonitrile （A） and 0.05% aqueous phosphoric acid （B） as the mobile phase. The detection wavelength was 237 nm, the column temperature was 35 ℃, the flow rate was 1.0 mlEmin, and the injection volume was 10μL. Results： The calibration curves of evodia lactone, evodiamine, rutaecarpine, liquiritin, and glycyrrhizin showed good linear relationships （r〉0.99）. The recoveries of evodia lactone, evodiamine, rutaecarpine, liquiritin, and glycyrrhizin were 96.59%, 104.18%, 101.91%, 97.75%, and 97.95%, respectively. The concentrations of the components in processed Fructus Evodiae were obviously different to those in unprocessed Fructus Evodiae. Conclusions： The developed method is rapid and accurate. The results provide a reference for processed Fructus Evodiae and the changes that could be expected in its effects compared to unprocessed Fructus Evodiae.

不同生长年限对三叉苦种子及药材质量的影响

研究不同生长年限三叉苦[Evodia lepta(Spreng.)Merr.]种子及药材的质量,以探讨三叉苦种子最佳采收时期和药材采收年限。结果表明,当三叉苦植株长到三年生时,其种子活力和发芽率均达到最高,同时其产量和质量均较高。产业化推广种植3年即达到野生三叉苦的产量,且质量更优于野生药材,建议产业化推广种植3年以上采收。

New therapy for oral ulcer:Evodia rutaecarpa patch combined with acupoint application

Background:Oral ulcer is the most common and easily recurrent disease in stomatology,which influence the patients’communication,normal dietary,and sleep.Evodia rutaecarpa(ER)is a traditional Chinese herbal medicine recorded in ancient Chinese medical books,which has a medicinal history of more than 2,000 years.Clinically,the application of ER at plantar Yongquan point(KI1)is effective in the treatment of oral ulcer.The purpose of this study was to combine the modern transdermal drug delivery system with traditional Chinese medicine to develop the transdermal absorption patch of ER and apply it to the treatment of oral ulcer at Yongquan point of plantar.Methods:Firstly,the medicinal materials of ER were extracted and the extracted materials were prepared into dispersed ER patch.The formulation and preparation process were screened by orthogonal design method and single factor investigation method.The adhesive and transdermal properties of the patch were used as the evaluation index of the preparation.Secondly,Wistar rats were used as experimental animals to establish a rat model of mouth ulcers.Wistar rats were randomly divided into normal group,model group(A),model group(B),low dose group,medium dose group and high dose group.the efficacy of ER on rat’s oral ulcer model was evaluated through three aspect such as apparent index,pathological index and biochemical index.Results:The patch had suitable adhesion and good skin penetration,which was an effective treatment for oral ulcer.In vivo pharmacodynamic studies,compared with the normal group,the body mass and food intake of rats in each group after modeling decreased,the amount of drinking water increased,the tissue structure of oral mucosa was damaged,and the levels of inflammatory factors(TNF-α,IL-6)and malondialdehyde increased,the levels of anti-inflammatory factors(IL-10),cell growth factor(epidermal growth factor,TGF-β_(1))and superoxide dismutase decreased.Compared with the model group,the body weight and food intake of each dosing group increased,water consumption decreased,the oral mucosal tissue structure was more complete,the levels of TNF-α,IL-6 and malondialdehyde decreased,the levels of IL-10,epidermal growth factor,TGF-β1 and superoxide dismutase increased,and the changes of various indexes were dose-related.Conclusion:ER patch can inhibit inflammatory reaction,enhance the antioxidant defense ability of the body,and promote the repair of damaged oral mucosa,so as to play an effective role in the treatment of oral ulcer.

吴茱萸HPLC指纹图谱的建立及3种成分含量的测定

[目的]建立吴茱萸(FRUCTUS EVODIAE)药材的指纹图谱,并对吴茱萸药材中绿原酸、金丝桃苷和吴茱萸碱进行同时测定。[方法]HPLC条件为:Hypersil C18色谱柱(250.0 mm×4.6 mm,5μm);流动相为乙腈-1%乙酸水溶液,梯度洗脱;流速为1.0 ml/min;检测波长为270nm;进样量为10μl。[结果]不同产地的吴茱萸药材指纹图谱共有19个共有峰,共有峰相对保留时间RSD值小于2.50%,相对峰面积RSD值为2.10%。整体来看,江西栽培的吴茱萸药材中绿原酸、金丝桃苷和吴茱萸碱含量要高于贵州、云南等地吴茱萸药材。[结论]该研究首次建立了吴茱萸药材的指纹图谱并同时测定了吴茱萸药材中的绿原酸、金丝桃苷和吴茱萸碱含量,为不同产地、不同采收期吴茱萸药材的质量评价提供了更好的技术手段。

吴茱萸中7种活性成分的含量测定

[目的]采用高效液相色谱及紫外检测法建立同时测定吴茱萸药材中辛弗林、绿原酸、芦丁、金丝桃苷、槲皮素、吴茱萸碱和吴茱萸次碱7种活性成分含量的方法。[方法]采用浓度为50%的甲醇-水溶液超声制备样品。以Hypersil C18(5μm,250 mm×4.6 mm)为色谱柱,以乙腈-乙酸(V/V,1%)水溶液为流动相进行梯度洗脱。在254 nm波长下检测芦丁、金丝桃苷和槲皮素的含量;在270 nm波长下检测辛弗林和吴茱萸碱的含量;在340 nm波长下检测吴茱萸次碱和绿原酸的含量。[结果]辛弗林、绿原酸、芦丁、金丝桃苷、槲皮素、吴茱萸碱和吴茱萸次碱各成分分离效果良好;其平均回收率均接近100%,RSD均小于3.1%。[结论]该方法适用于同时测定吴茱萸药材中辛弗林、绿原酸、芦丁、金丝桃苷、槲皮素、吴茱萸碱和吴茱萸次碱的含量,为吴茱萸药材的质量评价提供了更好的技术手段。

Chemical constituents of the unripe fruits of Evodia rutaecarpa

Aim To investigate the chemical constituents of the unripe fruits of Evodia rutaecarpa （Juss.） Benth. and provide a scientific basis for its quality control. Methods The compounds were isolated by silica gel column chromatography and identified by spectral analysis. Results Sixteen compounds were identified as evodiamine （1）, rutaecarpine （2）, β-sitosterol （3）, isorhamnetin（4）, evodol （5）, quercetin （6）, limonin （7）, wuzhuyurutine A （8）, evodirutaenin （9）, shihulimonin A （10）, wuzhuyurutine B（ll）, wuchuyuamide Ⅰ （12）, daucosterol （13）, trans-caffeic acid methylate （14）, dehydroevodiamine （15）and sucrose （16）. Conclusion Compounds 4, 6, 10 and 14 were isolated from the title plant for the first time.

中药吴茱萸的微量元素分析及TE图谱

中药吴茱萸是一种较为常用的中药,也是贵州的名药之一。其基源是芸香科吴茱萸植物。一般认为是吴茱萸Evodia rutaecarpa(Juss)Bcnth及其变种石虎E.rutaecarpa.var,officinilis(Dode)Huang、波氏吴茱萸E.rutaccarpa var,bodinieri(Dode)Huang的果实。但其种以下的分类则有争议。在药材上吴茱萸也有不少混乱品种。

A new strategy of enhancing absorptivity and safety for evodiamine: polyamidoamine derivatives modified by polyethylene glycol chain

Background:Traditional Chinese medicine involves complex ingredients and mixtures of ingredients that often exhibit low bioavailability,and excipients are often lacking to increase the absorption-enhancing effects.This study modified the generation 4 polyamidoamine dendrimer with polyethylene glycol of different molecular weights(5000,2000,1000)to form a series of polyamidoamine-co-polyethylene glycol(PAMAM-co-PEG)as a novel class of oral absorption enhancers.Evodiamine,the major alkaloid found in the traditional Chinese medicine Wu Zhu Yu(Fructus Evodiae),was used as a model drug to verify the absorption-enhancing effects and the safety of this alkaloid.Methods:This study utilized the solubility determination method documented in the Pharmacopoeia of the People’s Republic of China(2015 edition)and the D0 values recommended in the US FDA guidelines to comprehensively evaluate the solubility of evodiamine.The permeability of evodiamine was assessed using the apparent permeability coefficient in experiments based on in vitro cell models.Multiple aspects of the biological safety of PAMAM-co-PEG were explored using the MTT assay,LDH assay,and total protein release of the rat intestinal tract.Moreover,the absorption-enhancing effects of PAMAM-co-PEG at different molecular weights on evodiamine were verified via the use of in vitro cell models and in vivo intestinal loop circulation experiments with rats.Results:Evodiamine exhibited low solubility and permeability and was classified into class IV compounds using the biopharmaceutical classification system.PAMAM-co-PEG 2000 demonstrated improvement in the biosafety and absorption-enhancement effect of evodiamine at a specific concentration.This study showed that 0.05%(w/v)of PAMAM-co-PEG 2000 increased the cumulative penetration of evodiamine via cell transport by 1.32 times,and 0.10%(w/v)of PAMAM-co-PEG 2000 increased the area under curve value of evodiamine by 1.31 times.Conclusion:Evodiamine possesses low solubility and permeability and leads to poor oral bioavailability and a certain degree of cytotoxicity.PAMAM-co-PEG 2000 was found to be a potentially safe and efficient oral absorption enhancer.The results of this study might create a foundation for the development of novel excipients suitable for the complex active ingredients of traditional Chinese medicine.

吴茱萸中总黄酮的提取及其抗氧化活性研究

以芸香科吴茱萸属植物吴茱萸(Evodia rutaecarpa)为原料,吴茱萸总黄酮的含量为指标,在单因素试验的基础上,采用正交设计法优化总黄酮的提取工艺。所得最佳提取工艺为乙醇体积分数70%、固液比1∶50、提取时间40 min、提取温度65℃,在此条件下总黄酮得率为8.82%。DPPH·自由基清除试验评价吴茱萸总黄酮体外抗氧化活性表明,吴茱萸总黄酮具有良好的抗氧化活性。

Two New Indole Alkaloids from Evodia rutaecarpa

Two new indole alkaloids. wuchuyuamide I and II were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth and their structures were elucidated on the basis of spectral data.

Evodiagenine and dievodiamine,two new indole alkaloids from Evodia rutaecarpa

Two new indole alkaloids,evodiagenine 1 and dievodiamine 2 were isolated from the fruits of Evodia rutaecarpa(Juss.) Benth. The structure of compounds 1 and 2 were elucidated by comprehensive spectroscopic analysis and compound 1 was confirmed by X-ray crystallographic analysis.

(±)-Evodiakine,A Pair of Rearranged Rutaecarpine-Type Alkaloids From Evodia rutaecarpa

(±)-Evodiakine(1a and 1b),a pair of rearranged rutaecarpine-type alkaloids with an unprecedented 6/5/5/7/6 ring system,were isolated from the nearly ripe fruits of Evodia rutaecarpa.Separation of the enantiomers have been achieved by chiral HPLC column.The structures of(±)-evodiakine were unambiguously elucidated by 1D and 2D NMR spectra,mass spectrometry,and single-crystal X-ray diffraction.Their absolute configurations were determined by comparison of experimental and calculated electronic circular dichroism spectra.A hypothetical biogenetic pathway for(±)-evodiakine was also proposed.Compounds 1a,1b,and the racemate(1)were tested for their cytotoxic and anti-inflammatory activities.

Erk1/2, CDK8, Src and Ck1e Mediate <i>Evodia rutaecarpa</i>Induced Hepatotoxicity in Mice

Evodia rutaecarpa (E.R.) is a commonly used Chinese herbal medicine. However, it exerts certain hepatotoxicity and the underlying molecular mechanism has not been clarified. In this study, we investigated the molecular mechanism involved in hepatotoxicity induced by E.R. Mice were treated with E.R. water- and ethanol-extract at dosage equivalent to 16.67 g crude-drug/kg body weight by intragastric administration once a day on 30 consecutive days. The effect of E.R. extract on liver, manifested by histopathologic effects, liver index, and blood biochemical indexes were tested. In addition, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in liver tissue were measured. The signaling transduction molecules were determined by antibody microarray assay, and verified by western blot. E.R. extract, either water- or ethanol-extract, can induce liver dysfunction. Signaling molecules, Erk1/2, Src, CDK8 and CK1e, were involved in this process. E.R. extract can induce Ck1e expression and phosphorylation of Erk1/2 and CDK8, and inhibit Src phosphorylation. Inflammatory cytokines in liver tissue, IL-1β, IL-6, IL-8, and TNF-α were markedly increased upon the treatment of E.R. extract. In conclusion, E.R.-induced hepatotoxicity was due to the expression of inflammatory cytokine, which was mediated through Erk1/2, Src, CDK8 and CK1e.

芸香科植物简介

芸香科植物与人们日常生活关系比较密切,如柑桔类植物的果实,是著名的水果,深为人们所喜食;有些植物可提取芳香油;有的供药用和作调味品;还有一些是著名的观赏植物和园林绿化树种。因此,本科植物,除了能提供大量果品外,还提供了医药、食品加工、轻工等方面的工业原料。一、如何上好“芸香科”这一内容要上好芸香科这一内容,讲清楚芸香科的特征,使学生认识一些芸香科的植物。

正品吴茱萸与伪品吴茱萸的鉴别

吴茱萸始载于《神农本草经》列为中品。性大热、味辛苦,有小毒。温中止痛,止呕。为芸香科(Rutaceae)植物吴茱萸Evodia rutaecarpa(Juss.)Benth。疏毛吴茱萸E.rutaecarpa(juss)Benth.var.bodinieri(Dode)Huang和石虎E.rutaecarpa(juss.)Benth.Var.Officinalis(Dode)Huang的干燥未成熟果实。主产于贵州、广西、四川等地。其性状呈五角状扁球形,或浅裂成梅花状,表面黑褐色或绿褐色、粗糙、有许多突起的点状油点,顶端裂成五瓣,有的则呈五角星状裂缝。基部有结节状宿萼,常有短小果柄。

Simultaneous Analysis of Thirteen Bioactive Components in Evodia rutaecarpa and Its Varieties by HPLC-DAD-MS

Objective To control the quality of Evodia rutaecarpa better.Methods An HPLC-DAD-MS/MS method was established for the rapid and efficient identification of bioactive constituents and for simultaneous quantitative analysis of four bioactive ingredients including evodiamine,rutaecarpine,dehydroevodiamine,and evodin in E.rutaecarpa,which was applied to evaluating eight samples of E.rutaecarpa and its varieties from different areas.Results Thirteen potentially bioactive constituents including one flavonoid glycoside,one limonin,four indoloquinazoline alkaloids,and seven quinolone alkaloids were identified in all samples and the contents of dehydroevodiamine,evodine,evodiamine,and rutaecarpine varied widely from 0.10% to 0.51%,0.49% to 3.12%,0.07% to 1.56%,and 0.10% to 0.69%,respectively.Conclusion This method is found to be convenient,fast,accurate,and it is facilitated to improve the quality control standard of E.rutaecarpa and related products.

Separation of Five Quinolone Alkaloids from Fruits of Evodia rutaecarpa by High-speed Counter-current Chromatography

Objective To develop a suitable method for the large-scale separation of quinolone alkaloids from the fruits of Evodia rutaecarpa by high-speed counter-current chromatography （HSCCC）. Methods Two solvent systems were developed for the separation method. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase at 35 oCwith the flow rate of 2 mL/min and rotation speed of 855 r/min. Results Using the described method, 1-methyl-2-undecyl- 4（1H）-quinoione （1）, evocarpine （2）, 1-methy-2-[（6Z,9Z}]-6,9-pentade-cadienyl-4- （1H）-quinolone （3）, dihydroevocarpine （4）, and the mixture （5） of 1-methyl-2-[（z^- 10-pentadecenyl]-4（1H）-quinolone （Va） and 1 -methyl-2-[（Z^-6-pentadecenyl]- 4（1H）-quinolone （Vb） could be isolated from a petroleum ether extract. They were identified by 1H-NMR, ~3C-NMR, and MS/MS, and the purities were 94.3%, 95.2%, 96.8%, 98.3%, and 96.8%, respectively. Conclusion Five quinolone alkaloids from the fruits of E. rutaecarpa could be systematically isolated and purified using HSCCC. The presented method is simple and efficient with good potentials on the preparation of reference substances, especially on the quality control of Chinese materia medica.

Treatment of 36 Cases of Recurrent Aphthous Ulcer with Acupoint Sticking Therapy

Objective： To observe the therapeutical effect of using the paste of Wu Zhu Yu （Fructus Evodia） for acupoint sticking combined with tonifying kidney, to treat the recurrent aphthous ulcer. Methods： Thirty-six cases ofreccurent aphthous ulcer due to kidney dificiency were treated with Wu Zhu Yu （Fructus Evodia） paste applying to Yongquan （KI 1）, and orally taking Liu Wei Di Huang Pill. Ten treatments made up one course, 2-3 d of interval between 2 courses. Then 1-year follow-up was made. Results： Twenty cases were cured, 12 cases improved, 4 cases failed. Conclusion： The method of using Wu Zhu Yu （Fructus Evodia） paste applying to acupoint Yongquan （KI 1）, integrated with the manipulation of strengthening kidney, can effectively shorten the duration of disease, improve the symptoms, and control recurrency, which is good for this disease.