Pyrrolizidine alkaloids from Cynoglossum furcatum

Two new pyrrolizidine alkaloids have been isolated from the roots of Cynoglossum furcatum. On the basis of chemical and spectroscopic evidence, structures of the compounds have been elucidated. They are lactodine (3), a monoster alkaloid and viridinatine (4), a pyrrolizidine diester alkaloid. The structure of lactodine is elucidated as 9-O-(-)lactyl heliotridine and viridinatine as 7-O-(-)viridifloryl echinatine.     

Pyrrolizidine alkaloids: Organohalogen derivative isolated from Senecio jacobaea (Tansy Ragwort)

Senecio jacobaea (Tansy Ragwort) has previously been reported to contain 6 hepatotoxic pyrrolizidine alkaloids (PAs). Utilizing high pressure liquid chromatography (HPLC) plus mass spectrometry, 3 additional pyrrolizidine alkaloids are described, including a second chlorinated pyrrolizidine alkaloid. These additional pyrrolizidine alkaloids, through a variety of products, appear to pose an increased human health hazard.     

吡咯里西啶生物碱的细胞毒性及致毒机制研究进展

吡咯里西啶生物碱广泛分布于6000多种高等植物中,是一类肝毒性很强的天然产物。吡咯里西啶生物碱在肝脏代谢成活性代谢物吡咯后产生肝毒性。利用体外细胞毒性研究方法评价吡咯里西啶生物碱的毒性,对于阐明吡咯里西啶生物碱的致毒机制,研究开发拮抗其毒性的药物及保证临床用药安全具有重要意义。本文对吡咯里西啶生物碱的细胞毒性及致毒机制的研究进展进行综述。     

含吡咯里西啶类生物碱植物与肝小静脉闭塞病

植物中的吡咯里西啶类生物碱(pyrrolizidine alkaloids,PAs)是引致肝小静脉闭塞病的主要原因之一。美国、英国和我国等许多国家都有与含PAs植物或草药相关的肝小静脉闭塞病或肝损害的报道。全球约有6000余种植物含PAs,主要为4个科某些属的植物,即(1)菊科的千里光属、橐吾属、泽兰属、菊三七属和蜂斗菜属;(2)紫草科的所有属;(3)豆科的猪屎豆属;(4)兰科的羊耳蒜属。我国有38种中草药含PAs,常用的有12种:千里光、狗舌草、菊三七、款冬、佩兰、泽兰、山紫菀、紫草、天芥菜、野百合、猪屎豆、羊耳蒜。PAs本身的毒性极低,但其代谢物有肝毒性。PAs致肝毒性的摄入量,成人通常为每日数毫克至数百毫克,但WHO认为致肝小静脉闭塞病的每日最低摄入量为0.015mg/kg,即相当于70kg体重成人每天1mg。肝小静脉闭塞病的主要临床表现为顽固性腹水、黄疸、肝大。肝小静脉闭塞病尚无特效疗法,主要为对症、支持治疗。近年有报道用糖皮质激素或肝素治疗,但疗效和安全性尚待研究。作者认为,我国应加强含PAs植物致中毒的教育和监测。     

Hepatotoxicity of Pyrrolizidine Alkaloid Compound Intermedine: Comparison with Other Pyrrolizidine Alkaloids and Its Toxicological Mechanism

Pyrrolizidine alkaloids (PAs) are common secondary plant compounds with hepatotoxicity. The consumption of herbal medicines and herbal teas containing PAs is one of the main causes of hepatic sinusoidal obstruction syndrome (HSOS), a potentially life-threatening condition. The present study aimed to reveal the mechanism underlying the cytotoxicity of intermedine (Im), the main PA in Comfrey. We evaluated the toxicity of the retronecine-type PAs with different structures to cell lines derived from mammalian tissues, including primary mouse hepatocytes, human hepatocytes (HepD), mouse hepatoma-22 (H₂₂) and human hepatocellular carcinoma (HepG2) cells. The cytotoxicity of Im to hepatocyte was evaluated by using cell counting kit-8 assay, colony formation experiment, wound healing assay and dead/live fluorescence imaging. In vitro characterization showed that these PAs were cytotoxic and induced cell apoptosis in a dose-dependent manner. We also demonstrated that Im induced cell apoptosis by generating excessive reactive oxygen species (ROS), changing the mitochondrial membrane potential and releasing cytochrome c (Cyt c) before activating the caspase-3 pathway. Importantly, we directly observed the destruction of the cell mitochondrial structure after Im treatment through transmission electron microscopy (TEM). This study provided the first direct evidence of Im inducing hepatotoxicity through mitochondria-mediated apoptosis. These results supplemented the basic toxicity data of PAs and facilitated the comprehensive and systematic evaluation of the toxicity caused by PA compounds.     

Pyrrolizidine alkaloids from Eupatorium portoricense

Three pyrrolizidine alkaloids were isolated from Eupatorium portoricense and their structures elucidated by spectroscopic methods as (-)-viridifloryl-supinidine (amabiline), (-)-viridifloryl-heliotridine (echinatine), and C12- O-acetyl-(-)-viridifloryl-heliotridine (O(12)-acetylechinatine).     

Toxicity of Senecio jacobaea and pyrrolizidine alkaloids in various laboratory animals and avian species

The chronic toxicity of tansy ragwort (Senecio jacobaea) to several herbivorous laboratory animals and to chicks and turkey poults was examined by feeding the dried plant as a component of a mixed diet. Gerbils, hamsters and guinea pigs were resistant to chronic toxicity. Gerbils were highly resistant, consuming over 3500% of their body weight of the dried plant, whereas susceptible species succumb to a tansy ragwort intake of 5–20% of their body weight. Guinea pigs and gerbils were resistant to the acute toxicity of injected monocrotaline, a pyrrolizidine alkaloid (PA). They were moderately resistant to acute toxicity of injected tansy ragwort alkaloids. Both chicks and turkey poults were susceptible to chronic toxicity of dietary tansy ragwort.     

橐吾属植物中肝毒吡咯里西啶生物碱的LC/MSn检测

目的橐吾属植物中微量成分肝毒吡咯里西啶生物碱(HPA)的检测。方法采用薄层色谱法(TLC)、液相色谱与多级质谱联用法(LC/MSⁿ)。结果对橐吾属22种植物进行了HPA的LC/MSⁿ法检测，其中18种橐吾属植物中检测到了HPA。结论利用LC/MSⁿ法首次检测到东俄洛橐吾等15种橐吾属植物含有不同类型和种类的HPA，应进一步进行提取、分离与鉴定，并研究其毒性与活性；对不同种类、不同来源的橐吾属植物材料应分别检测其HPA。     

Pyrrole alkaloids from Bolbostemma Paniculatum

Three pyrrole alkaloids were isolated from Bolbostemma paniculatum. Their structures were elucidated as 4-(2-formyl-5-methoxymethylpyrrol-1-yl)butyric acid methyl ester (1), 2-(2-formyl-5-methoxymethylpyrrol-1-yl)-3-phenylpropionic acid methyl ester (2) and α-methyl pyrrole ketone (3) by spectroscopic techniques. Among them, 1 and 2 are new compounds.     

Pyrrolizidine alkaloids in Pulmonaria obscura

Leaves, roots and rhizomes, and inflorescenses of Pulmonaria obscura from two localities and of two different growth forms within one site were analyzed by GC-MS for their content in pyrrolizidine alkaloids (PAs). In roots and rhizomes PAs of the lycopsamine type typical for the Boraginaceae could be detected, e. g. intermedine, lycopsamine, and their O(7)-derivatives. The total PA concentrations in roots and rhizomes lay between 0.026 and 0.158 mg/g dry weight. In leaves and inflorescenses, on the other hand, only trace amounts of PAs (below 0.4 ng/mg dry weight) could be detected. No significant differences in total concentration of PAs could be found between the two sites.     

Safety concerns of herbal products and traditional Chinese herbal medicines: dehydropyrrolizidine alkaloids and aristolochic acid

In many countries, including the United States, herbal supplements, tisanes and vegetable products, including traditional Chinese medicines, are largely unregulated and their content is not registered, monitored or verified. Consequently, potent plant toxins including dehydropyrrolizidine alkaloids and other potential carcinogens can contaminate these products. As herbal and food supplement producers are left to their own means to determine the safety and purity of their products prior to marketing, disturbingly often good marketing practices currently in place are ignored and content is largely undocumented. Historical examples of poisoning and health issues relating to plant material containing dehydopyrrolizidine alkaloids and aristolochic acids were used as examples to demonstrate the risk and potential toxicity of herbal products, food supplements, or traditional medicines. More work is needed to educate consumers of the potential risk and require the industry to be more responsible to verify the content and insure the safety of their products. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.     

The effect of pyrrolizidine alkaloids (Senecio vulgaris) on the liver mixed-function oxidase system

A model system to detect the toxicity of pyrrolizidine alkaloids (PAs) was explored. Using the liver S-10 fraction, the effect of PAs on aniline hydroxylase and aminopyrine N-demethylase was examined. PAs were toxic to the aminopyrine N-demethylase enzyme system while exerting no toxicity on the aniline hydroxylase enzyme system.     

天然产物中抗HIV生物碱类化合物的研究进展

近年来,从天然产物中寻找高效低毒的先导化合物已成筛选抗HIV药物的重要研究方向。生物碱类化合物作为一类重要的天然产物,数量众多,结构类型复杂,其中有多种抑制和阻断HIV感染的有效成分,通过实验室研究工作和临床用药观察,有望从中获得抗HIV的有效药物。以生物碱类化合物的化学结构为基础,将生物碱类化合物分为异喹啉类、喹啉类、大环类、哌啶类、莨菪烷类、吲哚类、咔唑类、海洋多环胍类、萜类、manzamine型生物碱等10类,对其抗HIV活性进行综述。     

Dehydroxysenkirkinium Chloride,a Quarternary Pyrrolium Salt from the Pyrrolizidine Alkaloid Senkirkine

Treatment of the otonecine alkaloid senkirkine with acetyl chloride affords several unstable substances which form a blue dye with Ehrlich reagent and thus allow the photometric determination of otonecines. The title compound could be isolated and shown to have a quarternary pyrrolium salt structure.     

Life history parameters of the two-spotted spider mite (Tetranychus urticae Koch) feeding on bean leaves treated with pyrrolizidine alkaloids

In this study we assess the effect of pyrrolizidine alkaloids (PAs) extracted from Lithospermum canescens on the biology of the two-spotted spider mite (Tetranychus urticae Koch). Lithospermum canenscens (Michaux) Lehm. (Boraginaceae) is a common prairie plant also known as Indian paint or hoary puccoon. A mixture of seven PAs with known chemical structures was used in this investigation. Mites treated with PAs showed a high mortality of juveniles, a decrease in female fecundity and a shortened longevity. The intrinsic rate of population increase (r(m)) was used as an indicator of T. urticae population performance after treatment with PAs. The r(m) value obtained with alkaloid-treated leaves was lower than that for mites developing on untreated leaves, which indicates that the mite population would develop much slower on treated plants. The results suggest that further studies should be performed to assess the possible use of PA extracts for spider mite control.     

Diterpenoid alkaloids from Aconitum kirinense

A new C₁₈-diterpenoid alkaloid, kirinenine A (1), was isolated from the root of Aconitum kirinense, along with eight known diterpenoid alkaloids. The structures of all compounds were characterized on the basis of extensive NMR and MS analyses and by comparison with literature values, and the new one was further confirmed by X-ray crystallographic diffraction. All the compounds were isolated from the title plant for the first time.     

Comparison of the toxicities of Senecio jacobaea,Senecio vulgaris and Senecio glabellus in rats

The toxicity of Senecio jacobaea, S. vulgaris and S. glabellus to rats was assessed in a feeding trial. The plants were of similar toxicity, with a plant dry matter intake of about 20% of initial body weight being a lethal dose. Gas chromatography-mass spectrometry analysis demonstrated the presence of seneciphylline, jacobine, jacozine and jacoline in S. jacobaea, senecionine and seneciphylline in S. vulgaris, and senecionine in S. glabellus. An unidentified alkaloid was also found in all three plants.