Abnormal Secondary Growth and Histochemical Localization of Alkaloids in Root System of Aconitum flavum Hand.-Mazz.

[Objective] The purpose of this study was to clarify the structure,growth pattern and histochemical localization of alkaloids in root system of Aconitum flavum Hand.-Mazz.[Method] Paraffin sectioning and histochemistry were employed for performing the analysis in this study.[Result] The root system of Aconitum flavum Hand.-Mazz.consists of taproot,lateral root and adventitious root.The primary structure of root system is normal,but secondary structure shows abnormal.The cambium and the extra cambium of taproot form a ＂U＂-shaped secondary vascular bundle and tertiary bundle in abnormal secondary structure.The sieve tube group is made of little sieve tube group which is differentiated from primary phloem and cambium.Meanwhile,the secondary xylem in tuberous root also appears to be a ＂U＂ shape.Parenchyma cells of secondary phloem occupy most of the tuberous root.The sieve tube group of tuberous root is mainly differentiated from parenchyma cell of secondary phloem.[Conclusion] The difference in abnormal secondary structure of taproot and tuberous root are attributed to their varied cambium compose and activity pattern.Alkaloids are mainly accumulated in parenchyma cell of the inside cortex and between bundle in taproot,while parenchyma of secondary phloem and pith in tuberous root.

Diterpene Alkaloids of Aconitum kirinense Nakai I.Lepe-nine and Kirinine A

wo diterpene alkaloids, lepenine and kirinine A were isolated for the first time from the roots of Aconitum kirinense Nakai. Their structures have been established by IR, HRMS, NMR analysis and chemical reactions, and kininine A was found to be a new C 20 diterpene alkaloid.

Effect of processing on the alkaloids in Aconitum tubers by HPLC-TOF/MS

According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry(HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine,and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.

Two New Norditerpenoid Alkaloids from Aconitum spicatum Stapf

Two new norditerpenoid alkaloids, spicatine A (1) and spicatine B (2) were isolated from the root of Aconitum spicatum. The new compounds were deduced on the basis of their spectral data (IR, HREIMS, EIMS, 1D, 2D-NMR). This is the first whole report on the isolation of diterpenoid alkaloids from the A.spicatum Stapf.

Two New Norditerpenoid Alkaloids of Aconitum nagarum

Two new norditerpenoid alkaloids were isolated from the roots of Aconitum nagarum.Their structures were elucidated as 13-hydroxyfranchetine 1 and 10-dehydroxyflavaconitine 2,respectively, by 1D and 2D NMR experiments.

Two new C18-norditerpenoid alkaloids from Aconitum delavayi

Further phytochemical investigation of the unique C 18-norditerpenoid alkaloids from the roots ofAconitum delavayi Franch led to the isolation of two new norditerpenoid alkaloids, delavaconitine F 1 and delavaconitine G 2. Their structures were determined from spectroscopic evidence.

Diterpenoid alkaloids from a Tibetan medicinal plant Aconitum richardsonianum var. pseudosessiliflorum and their cytotoxic activity

The chemical constituents from Aconitum richardsonianum var.pseudosessiliflorum were investigated.The roots of this plant were extracted three times with 90% EtOH at the room temperature.The ethanol extracts were combined and concentrated under reduced pressure to yield residue,which was suspended in water and successively partitioned with chloroform.The chloroform extraction was isolated and purified by silica gel and Sephadex LH-20 column chromatography.Six compounds were isolated and elucidated as delelatine（1）,isodelpheline（2）,3-acetylaconitine（3）,isoatisine（4）,nordhagenine A（5）and yunaconitine（6）.Compounds 1-5 were obtained from Aconitum Brunneum for the first time.Compound（1）showed significant cytotoxic activities（IC50=4.36 μM）against the human tumor cell line P388.

Two new C_(19)-diterpenoid alkaloids from roots Aconitum hemsleyanium var. atropurpureum

A new franchetine-type C19-diterpenoid alkaloid 3-hydroxyfranchetine 1 and a new aconitine-type C19-diterpenoid alkaloid atropurpursine 2 have been isolated from the roots of Aconitum hemsleyanium var. atropurpureum. The structures of these new alkaloids were established on the basis of spectral data.

Diterpenoid Alkaloids and One Lignan from the Roots of Aconitum pendulum Busch

Diterpenoid alkaloids have neroprotective activity.Herein,three napelline-type diterpenoid alkaloids 1-3,two aconitine-type diterpenoid alkaloids 4-5,and one isoquinline-type alkaloid 6,as well as one lignan glycoside 7,have been isolated from the roots of Aconitum pendulum Busch.Compounds 1 and 7 were new compounds,and their chemical structures were determined on the basis of nuclear magnetic resonance(NMR)spectra and mass spectrometry analysis.A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aβ_(1−42)aggregates.

Analysis of Norditerpenoid Alkaloids Extracted from Aconitum sinomantanum Nakai by Electrospray Ionization Tandem Mass Spectrometry

Electrospray ionization mass spectrometry（ESI-MS） was applied simultaneously in determining norditerpenoid alkaloids from the roots of Aconitum sinomantanum Nakai （RAS） based on molecular mass information. The tandem mass spectra（ ESI-MS^n） provided the alkaloidal structural information, through which the existence of these alkaloids was further confirmed. Accordingly, six known norditerpenoid alkaloids were simultaneously determined on the basis of their ESI-MS^n spectra. Furthermore, based on the diagnostic fragmentation pathways of alkaloidal MS^n, a rapid method for direct detection and characterization of alkaloids from an ethanolic extract of RAS was described.

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）.

Matrix Solid-phase Dispersion Extraction of Alkaloids from the Roots of Aconitum kusnezoffii Reichb

Matrix solid-phase dispersion（MSPD） was developed for the extraction of four alkaloids, including aconitine, mesaconitine, hypaconitine and deoxyaconitine, from the roots ofAconitum kusnezoffii Reichb. The determination of the analyte was carried out by high performance liquid chromatography with UV detection. The alkaline alumina was used as sorbent. The mixture of acetonitrile and water was used as elution solvent. Several extraction parameters, such as type of sorbent, the ratio of sample to solid support material, type of the elution solvent and the volume of the elution solvent were tested. Mean recoveries ranged from 93.16% to 102.73%, with relative standard deviations from 0.27% to 4.17%. With the extraction efficiency and time expenditure taken into account, MSPD extraction should be a comparatively good method.

Tangutidines A-C,Three Amphoteric Diterpene Alkaloids from Aconitum tanguticum

Three new diterpene alkaloids,tangutidines A-C(1-3),and four known alkaloids(4-7)were isolated from the whole plant of Aconitum tanguticum,from which amphoteric diterpene alkaloids(1-3)were obtained for the first time.The structures of 1-3 were elucidated by detailed interpretation of spectroscopic data,including MS and NMR data.All of them were evaluated for their cytotoxic activities.

New Alkaloids from Aconitum stapfianum

Nineteen alkaloids,including a new C19-diterpenoid alkaloid stapfianine A(1)and a new benzamide derivative stapfianine B(2)were isolated from the roots of Aconitum stapfianum.Their structures were established on the basis of extensive spectroscopic analyses(IR,HRESIMS,1D and 2D NMR).

Diterpenoid Alkaloids from the Aerial Parts of Aconitum flavum Hand.-Mazz

Sixteen diterpenoid alkaloids(DAs),including six aconitine-type alkaloids(5 and 9−13),seven 7,17-seco-aconitine-type alkaloids(1−4,6−8),two napelline-type alkaloids(14 and 15)as well as one veatchine-type alkaloid(16),were isolated from the aerial parts of Aconitum flavum Hand.-Mazz.In which,flavumolines A−D(1−4)were four new ones,and flavu-moline E(5)was reported as natural compound for the first time.Their chemical structures were elucidated by the analysis of extensive spectroscopic data.The inhibitory activities of these isolates on Cav3.1 low voltage-gated Ca^(2+)channel,NO production in LPS-activated RAW264.7cells,five human tumor cell lines,as well as acetylcholinesterase(AChE)were tested.

Kiridine, A C18-Diterpene Alkaloid from Aconitum kirinense

Kiridine, a new C18-diterpenoid alkaloid, was isolated from the roots of Aconitum kirinense. Its structure was elucidated by MS, 1D- and 2D- NMR, and mono-crystal X-ray analysis. It is the first norditerpene alkaloid containing a 9,14-methylenedioxy group and the substituent at C-14 is (-configuration.

FUZITINE_z A NEW APORPHINE ALKALOID FROM FU ZI (ACONITUM CARMICHEALI DEBX)

A new aporphine alkaloid, named fuzitine, was isolated from the tuber of Aconitum carmicheali Debx, and its chemical structure was established'on the basis of spectral analysis and chemical reaction.

乌头属中药的毒性及毒代动力学研究进展

包括草乌、川乌、附子等在内的乌头属中药因其药理作用独特、药理活性显著,长期以来被用作治疗疾病的药物,或者作为一些新药开发设计的出发点,因此,乌头属中药应用广泛,具有一定的研究价值。尽管乌头属中药的药效显著,有难以替代的疗效,但其具有的毒性作用依旧不容忽视,对其的临床使用使得医、患担心,因此人们长期以来都在尽力研究乌头安全使用的方法和手段,致力于挖掘运用中药乌头独特的药理活性的同时,也在深入研究预防乌头属植物中毒的手段。毒代动力学的研究是评估药物药效、毒性作用、药物安全性评估及中毒推断的一种重要手段,用以解释药物暴露毒性实验结果和预测人用药物治疗不良反应的方法之一。因此,综述了中药乌头的毒性和毒代动力学研究方法,以期为乌头属中药的增效减毒的研究,如降低心脏毒性,保留其抗风湿性关节炎等药理活性,安全使用和中毒法医相关推断的研究提供参考,并对乌头属植物的使用前景进行展望。

乌头生物碱及其代谢物在家兔体内的死后弥散规律

目的探究乌头生物碱及其代谢物在中毒家兔体内的死后弥散规律,为乌头生物碱中毒相关死亡案件生前服毒或死后染毒的判别提供参考依据。方法将24只家兔经气管夹闭处死1 h后,以生川乌水煎液灌胃(以生川乌水煎液中乌头碱的LD50计算)。灌胃后将家兔以仰卧位保存于25℃气候箱中,分别于0 h、4 h、8 h、12 h、24 h、48 h、72 h、96 h随机各取3只进行解剖,取心血、外周血、尿液、心脏、肝、脾、肺和肾组织,采用高效液相色谱-串联质谱法对乌头生物碱及其代谢物在各生物检材中的含量进行检测。结果灌胃后4 h,乌头生物碱及其代谢物在心血、外周血和主要器官组织中均可检出,且含量随保存时间的延长发生动态变化。其中,脾、肝和肺中乌头生物碱及其代谢物含量均较高,尤其距离胃较近的脾中乌头生物碱及其代谢物含量最高。灌胃后48 h,家兔脾中代谢物苯甲酰新乌头原碱的平均质量分数最高;肾中乌头生物碱及其代谢物含量均偏低;尿液中未检出乌头生物碱及其代谢物。结论乌头生物碱及其代谢物在中毒家兔体内存在死后弥散现象,且从含量高的器官(胃)扩散到其他主要器官组织及心血中,其主要机制是顺浓度梯度的弥散,而尿液不受死后弥散的影响,可考虑将其作为乌头生物碱生前服毒和死后染毒的鉴别依据。