Cytotoxic Cycloartane Triterpenoid Saponins from the Rhizomes of Cimicifuga foetida

To enrich the bioactive cycloartane triterpenoid glycoside named actein and find out more cytotoxic cycloartane triterpenes,a phytochemical study of Cimicifuga foetida was conducted.113 g(0.17%)actein was purified by recrystallization while eight cycloartane-type triterpenes(1-8)were isolated from the mother liquid.The chemical structures of new compounds(1-4)were elucidated by 1D and 2D NMR and HRESIMS spectroscopic analyses.Moreover,new compounds showed moderate and broad-spectrum cytotoxicity against 5 human cancer cell lines with IC_(50) values ranging from 4.02 to 15.80μM.

Six New 9,19-Cycloartane Triterpenoids from Cimicifuga foetida L.

Six new 9,19-cycloartane triterpene derivatives,as well as 3 known analogues(7–9),were isolated from the roots of Cimicifuga foetida L.Their structures were established on the basis of extensive spectroscopic analyses(IR,UV,ORD,HRESIMS,1D and 2D NMR).

Cycloartane Glycosides from the Roots of Cimicifuga foetida with Wnt Signaling Pathway Inhibitory Activity

Four new 9,19-cycloartane triterpenoids,cimilactone E(1),cimilactone F(2),20-O-(E)-butenoyl-23-epi-26-deoxyactein(3),and 20,12b-O-diacetylcimiracemonol-3-O-b-D-xylopyranoside(4),together with four known constituents(5–8)were isolated from the roots of Cimicifuga foetida.The new structures were elucidated by extensive spectroscopic analysis.In addition,compounds 7 and 8 showed significant Wnt signaling pathway inhibitory activity,with IC50 values of 3.33 and 13.34 lM,respectively,using the luciferase reporter gene assay.

Two New Acetyl Cimicifugosides from the Rhizomes of Cimicifuga Racemosa

Two new acetyl cimicifugosides were isolated from the rhizomes of Cimicifuga racemosa. Their structures were elucidated as 2＇-O-acetyl cimicifugoside H-1 1 and 3＇-O-acetyl cimicifugoside H-1 2 by the spectroscopic evidence and chemical methods.

Development and Characterization of Microsatellite Markers for Three Pollination Morphs of <i>Cimicifuga simplex</i>(Ranunculaceae)

Cimicifuga simplex Wormsk. (Ranunculaceae) is a perennial herb distributed in eastern and northeastern Asia for which at least three different pollination morphs have been reported. It is classified as endangered or near threatened in some Japanese regions, and its rhizome is commercially used as a crude drug. To examine genetic differentiation and gene flow among the three morphs, we developed eight microsatellite markers by using next-generation sequencing and estimated the genetic structure of C. simplex. We tested eight primer pairs on 93 individuals from six populations of C. simplex in Nagano, central Japan, and found that heterozygosity in morphs I and III was low compared to expected heterozygosity. Bayesian clustering performed with the STRUCTURE program clearly distinguished the three morphs of C. simplex, and only a little gene flow was detected among the morphs. These eight microsatellite markers are expected to be useful in conservation genetic studies of this species and for future conservation planning.

NEW CYCLOARTANE TRITERPENOID CIMISIDE E FROM CIMICIFUGA FOETIDA L.

This paper relates to the structural elucidation of a new cycloartane triterpene glycoside, namely cimiside E(1), which was newly isolatea from the rnizomes of Cimicifuga foetida L.. Based on spectral evidence, its structure has been established as 25-anhydrocimigenol-3-O-β-D-xylopyranoside(23R, 24S).

STUDIES ON THE TOTAL SYNTHESIS OF CIMICIFUGAMIDEFROM CIMICIFUGA DAHURICA

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CIMICIFUGAMIDE AND ISOCIMICIFUGAMIDE,TWO NEW CINNAMAMIDE DERIVATIVES ISOLATED FROM CIMICIFUGA DAHURICA

Two new cinnamamide derivatives designated as cimicifugamide((?))and isocimicifu- gamide((?)),have been isolated from the rhizomes of Cimicifuga dahurica(Turcz.)Maxim..Their structures were established based on spectral evidence as N-(3'-methoxy-4'-hydroxyphenethyl)- 4-0-β-D-galactopyrano syl-ferulamide(E)and N-(3'-methoxy-4'-hydroxyphenetnyl)-4-0-β-D-ga- lactopyranosyl-isoferulamide(Z)respectively.

从兴安升麻(Cimicifuga dahurica Maxim.)分离的解痉物质

毛莨科（Ranunculaceae）升麻属（Cimicifuga）植物的茎根在日本和中国民间作为解热、镇痛、解痉以及治疗子宫下垂用药。作者用豚鼠离体空肠进行药理实验,以氯化乙酰胆硷、盐酸组织胺和氯化钡作为致痉物质,从兴安升麻的茎根中分离出有解痉作用的物质。茎根的50%甲醇提取物能抑制上述三个致痉物质的收缩作用。将该提取物以氯仿重复浸渍三次,溶于氯仿的活性物质在10-4～10-5克/毫升浓度下能缓解10-7克/毫升氯化乙酰胆硷所致的痉挛作用的一半。氯仿部分经硅胶柱层析后得到四个结晶物质,其中呋喃色酮类的齿阿米醇（Visa-mminol）和齿阿米素（Visnagin）以豚鼠离体空肠进行药理实验比较,证明其解痉作用分别是盐酸罂粟硷的1/3和1/10。

Efficacy and safety of Cimicifuga foetida extract on menopausal syndrome in Chinese women

Background It is now recognized that Cimicifuga foetida extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. This paper compares the clinical effects of different regimens of three-month course on climacteric symptoms in Chinese women, so as to evaluate the efficacy and safety of Cimicifuga foefida extract. Methods This was a prospective, randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into 3 groups to take different kinds of medicine for 3 months; participants were given Cimicifuga foefida extract daily in group A （n=32）, given estradiol valerate and progesterone capsule cycle sequentially in group B （n=32）, and given estradiol valerate and medroxyprogesterone acetate cycle sequentially in group C （n=32）. The questionnaires of Kupperman menopause index, Menopause-Specific Quality of Life, and Hospital Anxiety and Depression Scale were finished before and after the treatment. The status of vaginal bleeding and breast tenderness was recorded every day. Results Eighty-nine participants （89/96, 92.7%） completed the treatment. Kupperman menopause index decreased after taking the medicine for 3 months in each group （with all P〈0.001）, but the score after the treatment was higher in group A than in the other 2 groups. Except for the score of sexual domain in group A （P=0.103）, the scores of all domains of the Menopause-Specific Quality of Life decreased significantly after the treatment in all groups （with all P〈-0.01）. Score of anxity decreased significantly in group A （P=0.0l 5） and B （P=0.003）. Incidence of breast tenderness was 12.9% （4/31） in groupA, 36.7% （11/30） in group B, and 14.3% （4/28） in group C. Incidence of vaginal bleeding was 6.5% （2/31）in group A, 26.7% （8/30） in group B, and 82.1% （23/28）in group C. Conclusions Cimicifuga foeticla extract is effective and safe in the treatment of menopausal syndrome. It is worth extending its use in the treatment of climacteric complaints, especially among those having contradiction for hormone replacement therapy.

Cimicifuga heracleifolia is therapeutically similar to black cohosh in relieving menopausal symptoms: evidence from pharmacological and metabolomics studies

In the market of botanical dietary supplements, Cimicifuga heracleifolia(CH) has always been considered as an adulterated species of Cimicifuga racemosa(CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized(OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography(Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry(GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.

Photochemistry and pharmacology of 9,19-cyclolanostane glycosides isolated from genus Cimicifuga

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9, 19-cyclolanostane triterpenoid glycosides, which often exhibit extensive pharmacological activities. 9, 19-Cyclolanostane triterpenoid glycosides are distributed widely in genus Cimicifuga rather than in other members of the Ranunculaceae family. So far, more than 140 cycloartane triterpene glycosides have been isolated from Cimicifuga spp.. The aim of this review was to summarize all 9, 19-cyclolanostane triterpenoid glycosides based on the available relevant scientific literatures from 2000 to 2014. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.

Cycloartenol triterpenoid saponins from Cimicifuga simplex(Ranunculaceae) and their biological effects

The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.

初加工方式对升麻质量的影响

研究不同初加工方法对升麻质量的影响。选用不同初加工方法处理过的升麻,以《中国药典》2020年版中的方法分别测定各样品所含水分、灰分和浸出物的量,并以高效液相色谱法,建立异阿魏酸、咖啡酸、升麻素和升麻素苷的测定方法,测定各样品中各指标成分的含量。采用冷冻干燥法处理的药材所含水分最低,灰分最少,各指标成分含量最高,真空干燥法处理的药材浸出物含量最高,所建立的分析方法在一定的质量范围内线性关系良好,精密度高,稳定性、重现性好。综合对比,冷冻干燥法初加工的升麻质量更优。

Ultrasonographic Observation of the Breast in Early Postmenopausal Women during Therapy with Cimicifuga Foetida Extract and Sequential Therapy with Estrogen and Progestin

Background： It is now recognized that Cimicifuga foetida （C. foetida） extract is effective in alleviating menopausal symptoms. But the durations reported were usually short, The aim of this study was to investigate the effects of C. fl）etida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women. Methods： This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment. Results： In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A （11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P 〉 0.05）; in Group B glandular section thickness had increased significantly （10.98 ± 2.34 mm vs. 11.84± 2.72 mm and 11.90 ± 3.33 mm, P 〈 0.05） after treatment, the same as Group C （ 11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P 〈 0.05）. In comparing breast duct width betbre and after 1 and 2 years of treatment, no significant difference was seen in Group A （1.07 ± 0.19 mm vs. 1.02 ±0.18 mm and 0.98 ± 0.21 mm, P 〉 0.05）; in Group B the duct width had a downward trend after treatment （0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P 〈 0.05）, the same as Group C （ 1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P 〈 0.05）. The nodules detected before treatment had disappeared after 1 -year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment： There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check. Conclusions： In early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.

Bioactivity-based UPLC/Q-TOF/MS strategy for screening of anti-inflammatory components from Cimicifugae Rhizoma

In this study,the protective effects of Cimicifugae Rhizoma（CR） was demonstrated in Pseudomonas aeruginosa-induced pneumonia mouse model.To identify the anti-inflammatory ingredients,an ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）integrated nuclear factor κB（NF-κB） luciferase reporter assay screening system was carried out.As a result,some caffeic acid derivatives,including caffeic acid,ferulic acid/isoferulic acid,fukinolic acid,and cimicifugic acid ingredients were identified as the potential effective compounds from CR.For testing the anti-inflammatory capacity,caffeic acid was demonstrated to inhibit NF-kB and reduce the levels of IL-6 and IL-8 in TNF-α-treated BEAS-2B cells in a dose-dependent manner.Hence,CR preparations and its cinnamic acid derivatives have the possibility to be developed as a complementary therapy in the treatment of respiratory system infection in clinics.

基于网络药理学的黄连-升麻药对治疗复发性口腔溃疡中西医学机制探讨

[目的]探讨黄连-升麻药对治疗复发性口腔溃疡(recurrent aphthous ulcer,RAU)的现代药理机制,分析可能存在的中医治法相关疗效因素,进一步指导中医临床辨治。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索药物成分及靶点,通过在线人类孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库、人类基因组注释数据库(Human Genome Annotation Database,GeneCards)等检索疾病相关靶点,取交集后采用STRING平台进行蛋白互作(protein-protein interaction,PPI)分析,以CytoScape 3.7.2软件绘制PPI网络图并筛选出核心靶点,上传至MetaScape数据库,进行基因本体(gene ontology,GO)富集分析与京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析并构建网络图,利用AutoDock 4.2.6软件进行分子对接,并采用PyMOL软件将对接结果可视化。采用脊柱两侧注射完全弗氏佐剂的方法构建RAU大鼠模型;采用实时定量聚合酶链式反应(Real-time quantitative polymerase chain reaction,Real-time qPCR)检测各组大鼠口腔组织中核心靶基因的表达情况。[结果]筛选得到黄连、升麻活性成分共19个,靶点191个,药物与疾病交集靶点127个,药对干预RAU核心靶点23个,并依据连接度筛选出7个最关键的靶点,核心通路为白细胞介素-17(interleukin-17,IL-17)与肿瘤坏死因子(tumor necrosis factor,TNF)相关的信号通路。分子对接结果显示核心有效成分豆甾醇与各关键靶点均有较高的结合活性。动物实验发现,该药对可有效减少大鼠口腔溃疡数目。与空白对照组比较,模型组、低剂量组、中剂量组和高剂量组关键靶点表达明显更高(P<0.05);高剂量组靶点的mRNA相对表达和口腔溃疡数明显低于模型组、低剂量组、中剂量组(P<0.05)。[结论]黄连-升麻药对治疗RAU的分子机制,与其抗炎、保护口腔黏膜、调节免疫等作用有关,而相关的中医疗效机制涉及清热解毒、化瘀通络、托毒敛疮生肌等。

NOVEL ANTI-ANGIOGENIC ACTIVITIES OF A TRITERPENOID DEOXYACTEIN FROM CIMICIFUGA FOETIDA

Deoxyactein(DA)is a triterpenoid isolated from the root of Cimicifuga foetida which is a source of traditional Chinese herb'shengma'and is traditionally used as an antipyretic and analgesic agent.Previous studies showed that DA exhibited anti-proliferative effect in human breast cancer cells.Hence,the objectives of this study were to

正交试验法优选蜜升麻的炮制工艺研究

目的:探究蜜升麻的最佳炮制工艺。方法:采用高效液相色谱(HPLC)法测定蜜升麻中的异阿魏酸含量,色谱柱为Syncronis C18(250 mm×4.6 mm,5μm),流动相为甲醇-0.1%磷酸水(75∶25),流速为1.0 mL/min,柱温为30℃,检测波长为321 nm,进样量为10μL;采用正交试验法,以加热温度、加热时间、闷润时间作为考察因素,每一因素设4个水平,以蜜升麻中的异阿魏酸含量、性状外观评分的综合评分为指标进行考察。结果:异阿魏酸的线性范围为0.81~202.40μg/mL(r=0.9998),精密度、稳定性、重复性试验RSD值均小于2%,异阿魏酸的平均加样回收率为101.50%(RSD=1.66%);加热温度对试验结果具有显著影响(P<0.05),加热时间、闷润时间对试验结果影响不显著(P>0.05)。蜜升麻最佳炮制工艺为加热温度100℃、加热时间90 s、闷润时间90 min。结论:该炮制方法操作简便,工艺稳定可靠,可用于蜜升麻的炮制生产。

升麻化学成分及现代药理作用研究进展

升麻为毛茛科升麻属植物,在我国分布广泛、品种繁多,其药用历史已有两千余年。升麻化学成分复杂,其特征活性成分为Cycloartane型三萜。现代药理研究表明,升麻具有缓解围绝经期综合征、抗肿瘤、抗炎、抗病毒等作用,不同品种的升麻药材存在品质差异。对升麻化学成分、药理活性及药材品质进行文献归纳,分析升麻开发研究中存在的问题,旨在为升麻资源的深度开发提供参考。