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.

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.

Dynamic analysis of 10 components of the Chinese herbal compound Wuzhuyu-tang absorbed into rat plasma

To clarify the active components of Wuzhuyu-tang, this study analyzed dynamic changes of 10 ingredients of Wuzhuyu-tang in plasma using combination high performance liquid chromatography-mass spectrometry after oral administration in rats. The results showed that seven ingredients were detected in portal vein plasma after oral administration of 16.3 or 8.15 g/kg equivalent of raw material of Wuzhuyu-tang extract. The absorption rate of limonin, evodiamine, gingerol （6-Gi）, and ginsenoside-Rg1 was greater than that of isorhamnetin-3-O-β-D-glucosyl （6″→1″′）-α-L-rhamnoside, ginsenoside-Rb1 （Rb1）, and ginsenoside-Re （Re）. The time most elements were absorbed into the blood was 30 to 60 minutes after administration. Re, 6-Gi and Rb1 were metabolized faster. The results suggest that the seven ingredients described above are the active components for treating migraines.

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.

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.

Exploring the pharmacological mechanism of Wuzhuyu decoction on hepatocellular carcinoma using network pharmacology

BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.

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.

Exploring the mechanism of action of Wuzhuyu Decoction for vascular headache based on network pharmacology and molecular docking

Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.

吴茱萸盐热奄包在肛肠疾病术后腹胀护理的应用

目的探讨吴茱萸盐热奄包应用于肛肠疾病术后患者腹部胀气(简称“腹胀”)护理中的效果。方法选择厦门市中医院2022年5月—2022年11月收治的接受肛肠手术的患者114例,随机分为观察组(56例)和对照组(58例)。对照组采用常规手术后护理干预指导;观察组患者采用腹部按摩与吴茱萸盐热奄包联合护理。比较两组腹压、急性生理与慢性健康状况评分系统(APACHEⅡ)评分、肠鸣音恢复时间、胃肠蠕动恢复时间、首次排气时间、临床疗效、总满意度。结果观察组患者的腹压和APACHEⅡ评分明显低于对照组(P<0.05);观察组肠鸣音恢复时间、胃肠蠕动恢复时间与首次排气时间短于对照组(P<0.05);观察组治疗总有效率96.43%(54/56)高于对照组的81.03%(47/58)(P<0.05);观察组总满意度94.64%(53/56)高于对照组的82.76%(48/58)(P<0.05)。结论吴茱萸盐热奄包应用于肛肠疾病术后腹胀护理能够改善患者预后。

吴茱萸汤研究热点及趋势可视化分析

目的了解吴茱萸汤的研究现状、热点和趋势,为相关研究提供参考。方法检索中国知识资源总库(CNKI)、中文科技期刊数据库(VIP)、中国学术期刊数据库(万方数据)、中国生物医学文献数据库(CBM)建库至2023年2月28日收录的吴茱萸汤相关研究文献。采用NoteExpress3.6合并去重,通过CiteSpace6.1.R6软件绘制作者、机构、关键词知识图谱并进行解读。结果共纳入822篇文献,发文量呈波动上升趋势;主要来源期刊有《新中医》《河南中医》《四川中医》等;主要研究机构有北京中医药大学、中国中医科学院、山东中医药大学等;涉及566位作者,发文较多的有王智民(12篇)、龚慕辛(9篇)、毕开顺(5篇)等;高频关键词有“头痛”“《伤寒论》”“中医药疗法”等。结论吴茱萸汤治疗慢性胃炎、高血压等原发病疗效确切,是本领域研究热点;通过高效液相色谱等方法探索其活性成分、在分子水平上阐释其作用机制和作用靶点是本领域的研究趋势。

吴茱萸的活性成分和抗炎作用的研究进展

吴茱萸最先记载于《神农本草经》,被列为中品,该药用植物的药用部位是果实,其中的活性成分包括生物碱、黄酮、萜类、酚酸等,药理学研究发现吴茱萸在抗炎方面具有明显的效果,存在一定的研究价值。本文按其化学成分类别整理了吴茱萸成分抗炎机制的研究进展,为今后吴茱萸治疗炎症性疾病方面的临床研究提供参考。

Box-Behnken响应面法优化“五味子-吴茱萸”药对的提取工艺及含量测定

目的:优化“五味子-吴茱萸”药对提取工艺并测定其不同配伍的化学成分含量。方法:利用Box-Behnken设计在单因素考察的基础上考察“五味子-吴茱萸”药对的提取工艺,确定最佳提取工艺,并通过高效液相色谱法测定“五味子-吴茱萸”的化学含量,确定药对的最佳比例。结果:“五味子-吴茱萸”药对最优提取工艺为乙醇体积分数70%,料液比1∶15(g/mL),提取时间60 min,提取次数3次。该提取工艺科学可靠。结论:本研究方法简单可行,可为“五味子-吴茱萸”药对的开发利用及相关研究提供参考。

养血散寒通脉方治疗血虚寒凝型子宫内膜异位症的临床研究

【目的】观察养血散寒通脉方(由当归四逆加吴茱萸生姜汤加减而成)治疗血虚寒凝型子宫内膜异位症(EMS)的临床疗效。【方法】将120例血虚寒凝型EMS患者随机分为研究组和对照组,每组各60例。研究组给予养血散寒通脉方治疗,对照组给予少腹逐瘀颗粒治疗,疗程为3个月,并于疗程结束后随访1年。观察2组患者治疗前后各种疼痛评分[包括经期腹痛视觉模拟量表(VAS)评分和痛经、非经期盆腔痛、性交痛、盆腔压痛、骶韧带结节触痛分级评分]、卵巢子宫内膜异位囊肿大小及血清糖类抗原125(CA125)、血管内皮生长因子(VEGF)、可溶性细胞间黏附分子1(SICAM-1)、基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制因子2(TIMP-2)水平的变化情况,并观察2组患者的临床疗效、安全性、复发情况及妊娠情况。【结果】(1)研究过程中,研究组脱落3例,对照组脱落5例,最终共112例患者纳入统计分析,其中研究组57例,对照组55例。(2)治疗3个月后,研究组的总有效率为92.98%(53/57),对照组为85.45%(47/55),组间比较,研究组的疗效明显优于对照组(P<0.05)。(3)治疗后,2组患者的各种疼痛评分(包括经期腹痛VAS评分和痛经、非经期盆腔痛、性交痛、盆腔压痛、骶韧带结节触痛分级评分)均较治疗前明显下降(P<0.05),且研究组的下降幅度均明显优于对照组(P<0.05)。(4)治疗后,2组患者的卵巢子宫内膜异位囊肿均略有缩小,但组内治疗前后及治疗后组间比较,差异均无统计学意义(P>0.05)。(5)治疗后,2组患者血清CA125、VEGF、SICAM-1、MMP-9水平均较治疗前下降(P<0.05),血清TIMP-2水平均较治疗前升高(P<0.05),且研究组对血清CA125、VEGF、SICAM-1、MMP-9水平的下降幅度及对血清TIMP-2水平的升高幅度均明显优于对照组(P<0.05)。(6)随访1年,研究组的复发率为30.19%(16/53),明显低于对照组的68.09%(32/47),组间比较,差异有统计学意义(P<0.05)。研究组21例有生育要求,其中14例妊娠,妊娠率为66.67%(14/21);对照组20例有生育要求,其中4例妊娠,妊娠率为20.00%(4/20);组间比较,研究组的妊娠率明显高于对照组,差异有统计学意义(P<0.05)。(7)治疗期间,2组患者均无明显不良反应发生,且患者的血、尿、大便常规及心电图、肝肾功能等安全性指标均无异常变化。【结论】养血散寒通脉方治疗血虚寒凝型EMS患者疗效确切,能够显著缓解患者各种疼痛症状,改善妊娠结局,有效调节血清CA125、VEGF、SICAM-1、MMP-9、TIMP-2水平。

香薷挥发油对吴茱萸有效成分透皮吸收的影响

目的考察香薷挥发油对吴茱萸药效成分的促渗作用以及其促透皮吸收的能力。方法采用扩散池和大鼠离体皮肤进行体外透皮实验,以吴茱萸中多种成分作为指标,HPLC测定计算各成分累积透过量。HE染色、免疫组化染色、ATR-FTIR观察皮肤及角质层的变化,GC-MS测定挥发油给药后皮内贮存挥发油成分。结果香薷挥发油对吴茱萸中多种药效成分均具有促渗作用,与阳性药氮酮相比,香薷挥发油对金丝桃苷、吴茱萸碱、吴茱萸次碱的累积透过量更大。且香薷挥发油中倍半萜成分及含量占比最大的麝香草酚更易在皮肤中贮存,可以扰乱角质层脂质结构,促进药物的渗透。结论为透皮吸收促进剂的选择提供参考。

吴茱萸热罨包联合穴位贴敷治疗COPD无创通气患者腹胀的效果

目的观察吴茱萸热罨包联合穴位贴敷治疗慢性阻塞性肺疾病(COPD)无创通气患者并发腹胀的效果。方法选取南昌大学第二附属医院呼吸与危重症医学科收治的60例COPD无创通气腹胀患者作为研究对象,按照随机数字表法将其分为观察组和对照组,每组30例。对照组予常规治疗及护理,观察组在对照组基础上加用吴茱萸热罨包联合穴位贴敷,2组均连续治疗3 d。比较2组患者治疗前后的肠鸣音次数、腹围及临床疗效。结果治疗后观察组每分钟肠鸣音次数多于对照组(P<0.05),腹围小于对照组(P<0.05),治疗总有效率高于对照组(P<0.05)。结论吴茱萸热罨包联合穴位贴敷治疗COPD无创通气患者并发腹胀,可促进患者肠道蠕动,改善腹胀状况。

国医大师薛伯寿吴茱萸汤临床应用总结

吴茱萸汤具有暖肝温胃、降逆止呕、理气止痛之功效。国医大师薛伯寿认为吴茱萸汤主治病证为阳明中寒呕吐证、少阴中寒吐利证、厥阴肝寒犯胃头痛证。病证虽不同,病机则一,即肝寒犯胃、胃中虚寒、浊阴上逆。临证应活用吴茱萸汤,通过灵活合用经方时方治疗多种疑难病症,提高疗效。薛伯寿用药轻灵,配伍巧妙,药简效宏,值得借鉴学习。

吴茱萸汤治疗呕吐的方证关系研究

目的:探索吴茱萸汤治疗呕吐的方证关系。方法:从中国知网数据库检索吴茱萸汤治疗呕吐的医案100个,将医案中的相关症状(体征)、治法、药物等信息进行规范化处理,建立数据库。应用关联规则数据挖掘方法分析医案中症状(体征)、药物、治法的频数、支持度、置信度、提升度及其关联关系。结果:收集到的100个医案共涉及166个症状(体征),1432频次,其中以呕吐为首出现频次较高的症状(体征)19个;共涉及75味中药,671频次,其中以吴茱萸为首出现频次较高的中药13味;共涉及治法37种,385频次,其中以“降逆”为首出现频次较高的治法7种。共涉及提升度≥1.3的症状(体征)关联规则16个,提升度≥1.2的中药关联规则6个,均具有明显的核心化倾向。结论:运用关联规则的数据挖掘方法可以较好发现吴茱萸汤及其加减方治疗呕吐的症状(体征)、药物组方及治法的关联规律,可为临床遣方用药提供依据。