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.

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.

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.

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。

吴茱萸研究进展及在化妆品中的应用展望

综述吴茱萸所蕴含的丰富活性成分体系,核心成分涵盖生物碱、苦味素、挥发油、黄酮类化合物、酚酸及其多种衍生物。这些多样化的化学成分赋予吴茱萸显著的抗炎、抗光老化、抑制金属蛋白酶表达、广谱抑菌以及强大的抗氧化能力。展望了吴茱萸在化妆品行业的潜在应用价值与广阔前景。

HPLC法测定泡吴茱萸中柠檬苦素、吴茱萸碱和吴茱萸次碱含量

目的:建立用高效液相色谱法(HPLC)测定泡吴茱萸中柠檬苦素、吴茱萸碱、吴茱萸次碱三种成分的含量。方法:色谱柱为Eclipse XDB C18(4.6×250mm,5μm),流动相:A乙腈,B甲醇,C 0.05%磷酸溶液,各流动相配比为30∶20∶50,流速:1.000mL·min^(-1),检测波长:215nm,柱温:30℃。结果:柠檬苦素、吴茱萸碱、吴茱萸次碱三者依次在0.1303~1.6291μg(r=0.9995)、0.0500~0.6251μg(r=1.0000)、0.0354~0.4429μg(r=0.9999)范围内与其峰面积有良好的线性关系,且三者的平均加样回收率和RSD值分别为100.11%(RSD=0.7%)、100.74%(RSD=1.4%)和99.39%(RSD=1.3%)。结论:该方法操作简单,结果稳定,有着高准确度,适用于泡吴茱萸中柠檬苦素、吴茱萸碱、吴茱萸次碱含量的测定。

祛瘀生新法针刺联合吴茱萸穴位敷贴治疗脑出血失眠症临床研究

目的:观察祛瘀生新法针刺联合吴茱萸穴位敷贴治疗脑出血后失眠症的临床疗效。方法:选取93例脑出血后失眠症患者作为研究对象,按随机数字表法分为对照组46例和观察组47例。对照组给予西医常规及酒石酸唑比坦治疗,观察组在对照组基础上加用祛瘀生新法针刺联合吴茱萸穴位敷贴治疗。治疗1个月后,比较2组临床疗效、不良反应发生情况,以及治疗前后中医证候评分、匹兹堡睡眠质量指数(PSQI)评分、生活功能状态(KPS)量表、生活质量(IBS-QOL)量表评分、血生化指标[红细胞压积(HCT)、血管紧张素转化酶(ACE)、胱抑素C(CysC)、同型半胱氨酸(Hcy)]水平。结果:治疗后,观察组总有效率为95.74%,对照组为80.43%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组失眠日久、胸闷、夜寐不安、胸痛或头痛日久等中医证候评分及总分均较治疗前下降(P<0.05),且观察组上述各项评分均低于对照组(P<0.05)。治疗后,2组PSQI评分均较治疗前下降(P<0.05),且观察组PSQI评分均低于对照组(P<0.05)。治疗后,2组KPS、IBS-QOL评分均较治疗前上升(P<0.05),且观察组KPS、IBS-QOL评分均高于对照组(P<0.05)。治疗后,2组HCT、ACE、CysC、Hcy水平均较治疗前下降(P<0.05),且观察组4项血生化指标水平均低于对照组(P<0.05)。治疗期间,2组均未出现不良反应情况。结论:祛瘀生新法针刺联合吴茱萸穴位敷贴治疗脑出血后失眠症临床疗效显著,可有效改善患者中医证候、睡眠质量及氧化应激水平,提高生活质量。

扶正理气汤联合吴茱萸烫熨对剖宫产患者术后胃肠功能恢复的影响

目的探讨剖宫产患者术后应用扶正理气汤联合吴茱萸烫熨对胃肠功能恢复的影响。方法采用随机数字表法将2019年4月—2021年5月于高安市中医院行剖宫产术的76例患者分为两组,每组38例。对照组术后给予吴茱萸烫熨法治疗,观察组术后加服扶正理气汤治疗,均连续治疗2~3 d。比较两组胃肠功能恢复效果,胃肠功能相关指标恢复时间,术后腹胀、腹痛、胃肠反应程度及不良反应情况。结果观察组胃肠功能恢复总有效率为100.00%(38/38),高于对照组的84.21%(32/38);首次排气、排便时间及肠鸣音恢复时间较对照组短,术后48 h、72 h腹胀、腹痛及胃肠反应程度评分较对照组低,差异均有统计学意义(P<0.05)。两组均未见明显不良反应。结论剖宫产术后患者应用扶正理气汤联合吴茱萸烫熨,可促进胃肠功能恢复,减轻术后腹胀、腹痛及胃肠反应程度,且安全可靠,值得推广。

从厥阴经辨证应用当归四逆加吴茱萸生姜汤加味治疗混合型颈椎病

目的 探讨从厥阴经辨证应用当归四逆加吴茱萸生姜汤加味治疗混合型颈椎病(CS)的临床效果。方法 采用随机数字表法将2021年1月—2023年12月在本院就诊的50例混合型CS患者分为两组,每组25例。其中,对照组采用常规治疗,治疗组在对照组基础上从厥阴经辨证应用当归四逆加吴茱萸生姜汤加味治疗,两组均连续治疗4周。对比两组临床疗效、颈椎活动受限程度、疼痛程度、治疗满意程度、颈椎活动度和不良反应。结果 治疗组治疗总有效率较对照组高(P<0.05);治疗组治疗后颈痛量表(NPQ)各项评分及视觉模拟评分(VAS)较对照组低,田中靖久症状量表20分法各项评分及颈椎活动度较对照组高(P<0.05)。两组未见明显不良反应。结论 从厥阴经辨证应用当归四逆加吴茱萸生姜汤加味治疗混合型CS具有良好的效果,利于减轻患者疼痛及颈部受限程度,获得令人满意的治疗效果,值得推广。

吴茱萸粉穴位敷贴改善PCI术后焦虑、睡眠质量的疗效观察

[目的]观察吴茱萸粉穴位敷贴改善冠心病经皮冠状动脉介入(percutaneous coronary intervention,PCI)术后患者焦虑、睡眠质量的临床效果。[方法]选取2020年10月至2022年12月于杭州师范大学附属医院心内科住院的冠心病PCI术后患者60例,按照随机数字表法分为实验组和对照组各30例。两组人员均进行了常规西医治疗,对照组采用面粉糊,并加入和中药颜色一致的色素,制成同样大小和厚度的饼,行穴位敷贴治疗;实验组在常规西医治疗方案基础上,联合吴茱萸粉穴位敷贴患者两侧涌泉穴,20min/次,每周3次,2周为1个疗程。分别使用焦虑自评量表(self-rating anxiety scale,SAS)评分、匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)量表评价患者治疗前后的焦虑和睡眠质量。[结果]采用吴茱萸粉穴位敷贴后,实验组的焦虑检出率为3.33%,低于对照组的26.67%,差异有统计学意义(P<0.05);实验组PSQI评分为(4.83±2.04)分,显著低于对照组的(8.40±3.36)分,差异有统计学意义(P<0.05)。[结论]吴茱萸粉穴位敷贴有利于减轻冠心病患者PCI术后的焦虑状态,改善睡眠质量,值得进一步推广。

古今药汁制法演变及现代研究进展

本文分析并总结了药汁制炮制工艺的发展脉络、炮制作用,提炼药汁制炮制理论;综述了药汁制代表性中药的炮制前后化学成分变化、药效作用机制变化等现代研究进展,厘清药汁制中药炮制原理解析的研究思路,为药汁制工艺及传统炮制理论的继承与创新,解析炮制机理提供文献支撑。

吴茱萸化学成分及药理作用研究进展

吴茱萸为历代医家常用药,具有散寒止痛、降逆止呕、助阳止泻的功效,临床常用于治疗厥阴头痛、寒疝腹痛、经行腹痛等症。本文通过总结整理近10年吴茱萸的相关研究文献,发现吴茱萸主要含有生物碱类、萜类(包含苦味素类)、黄酮类、苯丙素类、蒽醌类、甾醇类及挥发油等成分,具有镇痛、抗炎、保护胃肠道及抗肿瘤等作用。吴茱萸的传统功效为温经止痛,现代虽有报道其具有镇痛作用,但是在温经方面的研究较少。吴茱萸所含的吴茱萸碱、吴茱萸次碱及苦味素类化合物为研究最广泛、最深入的药效成分,具有诸多药理活性,是吴茱萸的标志性成分,但目前关于吴茱萸毒理学的研究较少。

基于UHPLC-Q-TOF-MS/MS技术分析吴茱萸的化学成分

[目的]利用快速、灵敏的UHPLC-Q-TOF-MS/MS分析技术对吴茱萸药材的化学成分定性分析。[方法]色谱条件为ZORBAX Eclipse plus C_(18)色谱柱(2.1 mm×100 mm,1.8μm),水(0.2%甲酸)-乙腈(0.2%甲酸)为流动相,流速为0.3 mL/min,柱温30℃;采用电喷雾离子源,正负离子扫描检测,经PeakView软件对数据进行分析。[结果]共鉴定出64个化合物,包括生42个生物碱、8个柠檬苦素、8个黄酮苷、3个苯丙素和3个其他类型化合物。[结论]本实验方案能快速、精准地对吴茱萸的化学成分进行分析,为研究吴茱萸毒性成分和药效成分打下基础。

基于数据挖掘分析《中华医典·方书》黄连-吴茱萸药对的用药规律

目的 研究中医古籍中黄连-吴茱萸药对的用药规律。方法 基于数据库《中华医典·名方》检索历代方剂中包括黄连-吴茱萸药对的古籍文献,根据纳排标准进行筛选,并通过古今医案云平台网站进行分析。结果 收集符合筛选要求的原文264条,涉及中药233味,药性以温、寒、热为主,药味以辛、苦、甘较多,主要归脾经,主治疾病共44种,频次最高的为泄泻(23.87%)积聚和(21.97%),其次为痢疾(10.98%)、吐酸(8.71%)等。关联分析提示常用配伍,黄连-吴茱萸-干姜、黄连-吴茱萸-厚朴、黄连-吴茱萸-当归、厚朴-干姜、黄连-吴茱萸-柴胡、黄连-吴茱萸-茯苓、黄连-吴茱萸-人参、柴胡-厚朴、人参-厚朴、黄连-吴茱萸-木香。组方中治疗泄泻和吐酸的核心组方为黄连、吴茱萸,痢疾的核心组方为黄连、吴茱萸、当归;积聚的核心组方为黄连、吴茱萸、茯苓、柴胡、厚朴、干姜、人参、花椒、石菖蒲、桔梗;治疗腹胀的核心组方为黄连、吴茱萸、当归、木香、升麻、青皮、泽泻、草豆蔻、半夏、厚朴、柴胡、茯苓。黄连-吴茱萸比例为6∶1时仅治疗吐酸,1∶1时主治泄泻、积聚及痢疾,2∶1时可治疗痢疾、积聚,8∶3时主治积聚。结论 运用黄连-吴茱萸药对治疗消化系统疾病较多,比例及配伍不同治疗疾病不同。

不同基原吴茱萸药材中质量标志物预测分析:基于网络药理学和指纹图谱

目的:基于网络药理学和指纹图谱方法,预测吴茱萸药材中潜在的质量标志物(Q-Marker)。方法:应用网络药理学构建吴茱萸“成分-靶点-通路”网络,分析吴茱萸药材中的核心成分,运用高效液相色谱法建立18批吴茱萸及石虎药材指纹图谱,进行相似度评价及共有峰确认及指认,并采用多元统计分析,进一步验证吴茱萸药材中潜在的Q-Marker。结果:网络药理学研究结果表明,吴茱萸碱、吴茱萸次碱等在内的吲哚类生物碱成分及槲皮素、异鼠李素等其他有机酸类成分具有高连接度,是吴茱萸的主要活性成分。同时建立了药材指纹图谱,并指认其中7个共有成分,分别为新绿原酸、绿原酸、金丝桃苷、橙皮苷、去氢吴茱萸碱、吴茱萸碱、吴茱萸次碱。结合网络药理学活性和成分可测性以及Q-Marker理念,初步预测吴茱萸碱、吴茱萸次碱可作为吴茱萸药材潜在的Q-Marker,并进一步通过数理统计方法验证了Q-Marker体现药材共性的重要度。结论:结合网络药理学及特征图谱分析预测了吴茱萸的质量标志物,为阐明吴茱萸药效物质基础及作用机制提供了参考依据。