Norditerpenoid alkaloids from the processed tubers of Aconitum carmichaeli

Four new and five known norditerpenoid alkaloids were isolated from the processed tubers of Aconitum carmichaeli. The new alkaloids are 14-O-cinnamoylneoline (3), 14-O-anisoylneoline (4) 14-O-veratroylneoline (5), and lipo-14-O-anisoylbikhaconine (8). The known alkaloids are neoline (1), 14-O-acetylneoline (2), foresaconitine (6), crassicauline A (7), and lipohypaconitine (9). Alkaloids 2, 6, and 7 were isolated from this plant for the first time. The structures of the new alkaloids were established by spectroscopic and chemical methods.     

Chemical constituents of Lycoris albiflora and their cytotoxic activities

An alcoholic extract of Lycoris albiflora (Amaryllidaceae) showed potent cytotoxic activity against HL-60 cells with an IC50 value of 1.7 microg/mL. Phytochemical examination of the extract resulted in the isolation of 15 alkaloids, including two phenanthridine-type alkaloids (1, 2), one benzylphenethylamine-type alkaloid (3), two crinane-type alkaloids (4, 5), one pyrrolophenanthridine-type alkaloid (6), six lycorenan-type alkaloids (7-12), and three galanthamine-type alkaloids (13-15), together with three neolignans (16-18), two flavans (19, 20), and two acetophenone derivatives (21, 22). Compound 3 (hostasinine A) has not been isolated from Amaryllidaceae plants, and 1, 2, 4, 5, 7-9, 11, 12 and 14-22 are the first isolation and identification from L. albiflora. The phenanthridine-type alkaloids (1, 2), as well as the alkaloids (3-5), exhibited potent cytotoxic activities against not only HL-60 cells but also HSC-2 cells, thus leading to the conclusion that these alkaloids are mainly responsible for the cytotoxicity of the L. albiflora extract. Compound 1 (lycoricidinol), with the most potent cytotoxic activities, induced apoptosis in both HL-60 cells and HSC-2 cells. It is notable that 1 induced transient autophagy and morphological changes in mitochondria in the early stages of the apoptotic cell death process in HSC-2 cells.     

Comparative study of fourteen alkaloids from Uncaria rhynchophylla hooks and leaves using HPLC-diode array detection-atmospheric pressure chemical ionization/MS method

The purpose of the study is to compare alkaloid profile of Uncaria rhynchophylla hooks and leaves. Ten oxindole alkaloids and four glycosidic indole alkaloids were identified using HPLC-diode array detection (DAD) or LC-atmospheric pressure chemical ionization (APCI)-MS method, and a HPLC-UV method for simultaneous quantification of major alkaloids was validated. The hooks are characterized by high levels of four oxindole alkaloids rhynchophylline (R), isorhynchophylline (IR), corynoxeine (C) and isocorynoxeine (IC), while the leaves contained high level of two glycosidic indole alkaloids vincoside lactam (VL) and strictosidine (S). The presented methods have proven its usefulness in chemical characterization of U. rhynchophylla hooks and leaves.     

Studies of the intestinal absorption of the alkaloids in the Wu-tou decoction combined with different incompatible medicinal herbs in a Caco-2 cell culture system using UPLC-MS/MS

In this study, seven alkaloids were detected in Wu-tou decoction using ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MSn). The aim of this study was to investigate the effect of Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, Pinelliae Rhizoma in different ratios with Wu-tou decoction (2:1, 1:1, 1:2) by measuring the therapeutic effects in Wu-tou decoction of main seven alkaloids including benzoylaconitine (BA), benzoylmesaconitine (BM), benzoylhypaconitine (BH), hypaconitine (HA), fuziline (FU), niaolin (NE) and deoxyaconitine (DA). The permeability of aconitum alkaloids extract through a Caco-2 cell monolayer was analyzed in the absence and presence of Fritillariae Cirrhosae Bulbus, Fritillariae Thunbergii Bulbus, and Pinelliae Rhizoma, respectively. The results showed that Pinelliae Rhizoma could reduce the absorption of the alkaloids and increase the excretion of the alkaloids, which would attenuate the therapeutic effects of Wu-tou decoction. Therefore, Pinelliae Rhizoma is an incompatible herb of Wu-tou decoction because of the inhibition of the absorption of alkaloids in the intestine. And that Fritillariae Cirrhosae Bulbus and Fritillariae Thunbergii Bulbus showed the effects to improve the permeability of the alkaloids in Wu-tou decoction. These effects of these two herbs were similar, but the former was stronger than the latter, which most likely is due to the fact that the compositions of these two traditional Chinese medicines are similar. The in vitro data suggests that the compounds such as fritillary presented in alkaloids in the formula maybe improve the therapeutic function caused by the increased bioavailability of alkaloids in intestine.     

Alkaloids from the Roots of Stemona tuberosa

Four new alkaloids, didehydrotuberostemonine A ( 1 ), stemoninone ( 2 ), tuberostemospiroline ( 3 ), and tuberostemonine L ( 4 ), together with seven known alkaloids, were isolated from the roots of Stemona tuberosa. Their structures were elucidated on the basis of spectroscopic analysis. The known alkaloids were identified as 2‐oxostenine ( 5 ), tuberostemonine ( 6 ), sessilifoliamide H ( 7 ), tuberostemonone ( 8 ), didehydrotuberostemonine ( 9 ), bisdehydrostemoninine ( 10 ), and tuberostemoamide ( 11 ).     

New C19-diterpenoid alkaloids from Aconitum piepunense

Two new C(19)-diterpenoid alkaloids, piepunensine A (1) and 18-acetylcammaconine (2), have been isolated from the roots of Aconitum piepunense together with five known alkaloids pengshenine B (3), talatisamine (4), aconosine (5), yunaconitine (6), and talatizidine (7). The structures of the new alkaloids were established on the basis of spectral data (1D- and 2D-NMR, HR-MS).     

Investigation of Aconitine-type Alkaloids from Processed Tuber of Aconitum carmiechaeli by HPLC-ESI-MS/MS~n

Introduction Aconitine-type alkaloids isolated from the roots of Aconitum carmiechaeli show a potential toxicity and a broad spectrum of bioactivity[1-4].On the basis of the C8-substituent of C19-diterpenoid skeleton,aconitine-type alkaloids can be divided into diester-diterpenoid alkaloids(DDAs),monoester-diterpenoid alkaloids(MDAs),and lipo-alkaloids(Fig.1).     

云南蕊木茎中的抗炎吲哚生物碱

应用多种色谱和波谱学方法,从云南蕊木(Kopsia officinalis)茎中分离鉴定了27个单萜吲哚生物碱,包括7个新化合物kopsiofficines A^G和20个已知化合物.此外,建立脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症模型,通过测定IL-1β,PGE2和TNF-α炎症因子释放评价生物碱的抗炎活性.结果表明,kopsiofficines A(1),kopsiofficines B(2),kopsiofficines D(4),kopsiofficines F(6),kopsiofficines G(7),12-methoxykopsine(11),kopsinoline(15),(-)-N-methoxycarbonyl-11,12-methylenedioxykopsinaline(16),kopsinine(18)和kopsinic acid(20)表现出显著的抗炎活性,与阳性对照(地塞米松)基本相当.研究发现C-5位丙酮基取代的单萜吲哚生物碱的抗炎活性明显强于原型生物碱,推测丙酮基可能是抗炎活性的药效促进基团,研究结果为进一步的结构修饰和药理学研究提供了线索.     

Structural characterization and identification of C19‐ and C20‐diterpenoid alkaloids in roots of Aconitum carmichaeli by rapid‐resolution liquid chromatography coupled with time‐of‐flight mass spectrometry

Aconite alkaloids from the roots of Aconitum carmichaeli (Fuzi, in Chinese) have been investigated by rapid‐resolution liquid chromatography coupled with time‐of‐flight mass spectrometry (TOFMS) in positive mode. With dynamic adjustment of the key role as fragmentor voltage in TOFMS, an efficient transmission of the ions was achieved to obtain the best sensitivity for providing the molecular formula for each analyte, and abundant fragment ions for structural information. Fifteen authentic standards isolated from Fuzi with various structures were first characterized by TOFMS, including diester‐diterpenoid alkaloids (DDAs), monoester‐diterpenoid alkaloids (MDAs), alkylol amine‐diterpenoid alkaloids (ADAs), veatchine‐type alkaloids and atisine‐type alkaloids. Fragmentation rules and key diagnostic fragment ions have been summarized, and possible pathways of fragmentation have been proposed. By accurate mass measurements within 5 ppm error for each ion, 30 C₁₉‐diterpenoid alkaloids including 10 DDAs, 3 MDAs, 9 ADAs and 8 other type alkaloids, and 8 C₂₀‐diterpenoid alkaloids including 4 veatchine‐type alkaloids and 4 atisine‐type alkaloids could be identified in a methanolic extract of Fuzi. Some isomers of aconite alkaloids were also differentiated. Based on the differences between their fragmentation pathways and special fragment ions, each type of aconite alkaloids was differentiated. Copyright © 2009 John Wiley & Sons, Ltd.     

pH‐Zone‐refining counter‐current chromatography for two new lipo‐alkaloids separated from refined alkaline extraction of Kusnezoff monkshood root

An efficient and refined method for the separation of six aconitine‐type alkaloids from the alkaline prepared “Kusnezoff monkshood root” was established. It is the first study that two new lipo‐alkaloids were successfully isolated from refined sample by pH‐zone‐refining counter‐current chromatography rather than synthetic method. It was of interest that a great deal of lipo‐alkaloids was produced in crude extract from the alkalization of “Kusnezoff monkshood root.” A refined sample method was proposed to enrich two types of alkaloids by liquid–liquid extraction, i.e. lipo‐alkaloids and monoester‐diterpenoid alkaloids. The pH‐zone‐refining counter‐current chromatography was performed with an optimized two‐phase solvent system composed of n‐hexane‐ethyl acetate–methanol–water (3:5:4:5, v/v), where upper organic phase was added to 3 mmol/L triethylamine as a retainer and lower aqueous mobile phase was added to 3 mmol/L hydrochloric acid as an eluter. As a result, six aconitum alkaloids, including two lipo‐alkaloids (8‐lino‐14‐benzoylaconine, 8‐pal‐14‐benzoylaconine), three monoester‐diterpenoid alkaloids (14‐benzoylmesaconine, 14‐benzoylaconine, beyzoyldeoxyaconine), and one aconine alkaloid (neoline) were acquired from the plant at the same time. The anti‐inflammatory activities of the two new lipo‐alkaloids were compared to the six alkaloids in vitro, in cyclo‐oxygen‐ase‐2 inhibition assays. The separation mechanism of six alkaloids by pH‐zone‐refining counter‐current chromatography was illustrated.     

Application of capillary zone electrophoresis in the separation and determination of the principal gum opium alkaloids

We describe the use of capillary zone electrophoresis (CZE) for the qualitative and quantitative determination of major alkaloids (i.e., thebaine, codeine, morphine, papavarine and narcotine) in gum opium involving the analysis of alkaloids without derivatization or purification. Three extractions with 2.5% w/v aqueous acetic acid quantitatively extracted major alkaloids. The separation was carried out by CZE using a 7:3 mixture of methanol and sodium acetate (100 mM, pH 3.1) at a potential of 15 kV, with UV detection at 224 nm. Spiking of pure reference alkaloid standards in the opium extract was used for peak identification. The influences of buffer composition, pH and voltage on the separation of alkaloids were studied. The detection limit of each alkaloid dissolved in methanol was found to be 850 ng/mL (morphine), 450 ng/mL (thebaine), 500 ng/mL (codeine), 550 ng/mL (papaverine), and 500 ng/mL (narcotine) at an injection pressure of 300 mbar (injection volume, 4 nL) with a signal-to-noise ratio of 3:1. The external standard method was used for the quantification of alkaloids. The calibration plot was based on linear regression analysis. The relative standard deviation (RSD) for peak area and migration time was in the range of 1.03-3.56% and 0.34-0.69%, respectively. Percentage compositions (g%) of opium alkaloids in five gum opium samples were found to be in the range of 14.45-15.95 (morphine), 2.0-3.45 (codeine), 1.32-2.73 (thebaine), 0.92-2.37 (papavarine), and 3.85-5.77 (narcotine). The method developed is suitable for the routine analysis of major gum opium alkaloids in samples of forensic importance.     

Indole alkaloids from camptotheca acuminata

Five minor alkaloids were isolated from the seeds of Camptotheca acuminata Decne. Two of them are new indole alkaloids named camptacumotine (1) and camptacumanine (2) respectively. The others are known indole alkaloids naucleficine (3), angustoline (4) and dihydroisoquinamine (5), which was isolated for the first time from the plant.     

Qualitative and Quantitative Analysis of Drug Interactions: Fritillary Mediating the Transport of Alkaloids in Caco-2 Cells by P-Glycoprotein

Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry（UPLC-ESI-MS） was used to investigate the potential interaction between selected ingredients of Aconitum and fritillary. The efflux ratios of 14-benzoylmesaconine（BM）, 14-benzoylaconine（BC）, 14-benzoylhypaconine（BH）, mesaconitine（MA）, aco- nitine（AC） and hypaconitine（HA） was 11.16, 12.53, 11.69, 12.8, 11.03 and 6.15, respectively, and the secretion of them was inhibited by Veraparnil, which means they are the substrates of permeability-glycoprotein（P-gp）. The transport of Aconitum alkaloids extract through a Caco-2 cell monolayer was determined in the absence and presence of fritillary extract. And the fritillary extract increased the absorption of Aconitum alkaloids. Peimine（PE） and peimi- nine（PEN） in fritillary increased the absorption of pure Aconitum alkaloids. The transport of digoxin was respectively enhanced by PE and PEN, which means they are the inhibitors of P-gp. PEN showed more effective inhibition than PE at the same concentration. The in vitro data suggest that the compounds such as fritillary present in alkaloids were able to inhibit the P-gp activity and lead modifying the transport of alkaloids.     

Three new C_(20)-diterpenoid alkaloids from Delphinium anthriscifolium var.savatieri

Three new C20-diterpenoid alkaloids, designated as anthriscifolmines A-C (1-3), together with two known alkaloids denudatine and delgramine, were isolated from the whole herb of Delphinium anthriscifolium var. savatieri. The structures of these new alkaloids were elucidated on the basis of spectral data.     

Development of an HPLC‐DAD method for the determination of five alkaloids in Stephania yunnanensis Lo and in rat plasma after oral dose of Stephania yunnanensis Lo extracts

For the rational utilization and the quantitative quality control of the Stephania yunnanensis Lo, an HPLC‐DAD method was developed for the quantitative and simultaneous determination of five alkaloids in rat plasma (stepharine, sinomenine, palmatine, isocorydine and tetrahydropalmatine), which were the main active chemical constituents of this plant and belong to four kinds of isoquinoline‐type alkaloids (protoberberine, morphine, aporphine and protaporphine alkaloids). The contents of five alkaloids ranged from 0.09 to 2.32% (w/w). The method validation was tested for the linearity (r² > 0.9975), precision (intra‐day RSD < 4.8% and inter‐day RSD < 4.9%), extraction recovery (85.49 ± 2.29% to 99.21 ± 1.48%) and stability (98.5 ± 5.3% to 101.2 ± 3.4%). We developed an HPLC‐DAD method to simultaneously measure these alkaloids in rat plasma after oral administration of the extract of this plant to rats. The results supported the hypothesis that isoquinoline alkaloids were the compounds responsible for the main pharmacological activities for anti‐inflammatory and analgesic.     

金丝矮陀陀植物中甾体生物碱的分离与化学结构

最近,我们研究了云南产的金丝矮陀陀植物中的甾体生物碱。对植物样品的乙醇提取物作了系统分离,从中得到22个甾体生物碱,     

New bisbenzylisoquinoline alkaloids from Cocculus laurifolius

Two new bisbenzylisoquinoline alkaloids, alpha, alpha'-dioxo-7'-O-demethylstebisimine (1) and 7'-O-demethylstebisimine (2), along with 14 known alkaloids, were isolated from the roots of Cocculus laurifolius. These alkaloids were characterized mainly by spectroscopic methods.     

赣皖乌头生物碱的研究II. 江西兴国产赣皖乌头中其他生物碱的分离和鉴定

从江西兴国县赣皖乌头(Aconitum finetianum Hand-Mazz)根中分得五个二萜类生物碱,根据衍生物的制备、光谱分析及物理常数测定,证明其中两个为新生物碱,定名兴国乌头碱(finetianine)和1-去氢宋果灵(1-dehydrosongorine);其他三个为已知生物碱宋果灵(songorine)、诺密宁(nominine)和氨茴酰牛扁碱(anthranollycoctonine).     

Simultaneous determination of the content of isoquinoline alkaloids in Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids by high‐performance liquid chromatography with diode array detection

A simple and efficient method was developed for the simultaneous determination of eight isoquinoline alkaloids in methanol extracts of Dicranostigma leptopodum (Maxim) Fedde and the effective fractionation of the alkaloids of D. leptopodum by high‐performance liquid chromatography with diode array detection. The chromatographic conditions were optimized on a SinoChrom ODS‐BP column to obtain a good separation of the four types of alkaloid analytes, including two aporphines (isocorydine, corydine), two protopines (protopine and allocryptopine), a morphine (sinoacutine), and three quaternary protoberberine alkaloids (berberrubine, 5‐hydroxycoptisine, and berberine). The separation of these alkaloids was significantly affected by the composition of the mobile phase, and particularly by its pH value. Acetonitrile (A) and 0.2% phosphoric acid solution adjusted to pH 6.32 with triethylamine (B) were selected as the mobile phase with a gradient elution. With this method, a new quaternary protoberberine alkaloid was isolated and the two structural isomers (isocorydine and corydine) were baseline separated. The appropriate harvest period for D. leptopodum was also recommended based on our analysis. The method for the effective fraction of the alkaloids of D. leptopodum was optimized under this method with regard to the varying significant pharmacological activities of the alkaloids.     

高乌头根中新的二萜生物碱

从高乌头根中分离得到3个新的冉乌头型的C₁₈-二萜生物碱高乌宁己(1)、高乌宁庚(3)、高乌宁辛(5)和一个新的牛扁碱型C₁₉-二萜生物碱高乌宁壬(7). 它们的结构通过IR, ¹H NMR, ¹³C NMR, MS予以确证.