Cellular distribution of alkaloids and their translocation via phloem and xylem: the importance of compartment pH

The physico‐chemical background of alkaloid allocation within plants is outlined and discussed exemplarily for pyrrolizidine alkaloids (PAs) and nicotine. The trigger for this discourse is the finding that, for example, PAs, which are taken up from the soil, are translocated in the xylem, whereas – when genuinely present in plants – they are allocated as N‐oxides via phloem. Special emphasis is put on the impact of different pH values in certain compartments, as this entails significant changes in the relative lipophilic character of alkaloids: tertiary alkaloids diffuse readily through biomembranes, while the corresponding protonated alkaloids are retained in acidic compartments, i.e. vacuoles or xylem. Therefore, this phenomenon, well known as the ‘ion trap mechanism’, is also relevant for long‐distance transport of alkaloids. Any efficient allocation of typical tertiary alkaloids within the phloem can thus be excluded. In contrast, due to their strongly increased hydrophilic properties, alkaloid‐N‐oxides or quarternary alkaloids cannot diffuse through biomembranes and, consequently, would be retained in the acidic xylem during translocation. The major aim of this paper is to sharpen the mind for the chemical peculiarities of alkaloids and to consider them adequately in forthcoming investigations on allocation of alkaloids.     

Isoquinoline-derived alkaloids from the bark of Guatteria olivacea (Annonaceae)

Phytochemical investigation of the bark of Guatteria olivacea R. E. Fries (Annonaceae) led to the isolation and identification of ten isoquinoline-derived alkaloids, including three phenanthrenes, atherosperminine, argentinine, and atherosperminine N-oxide; three aporphines, asimilobine, puterine, and discoguattine; two oxoaporphines, liriodenine and oxoputerine; and two tetrahydroprotoberberines, corypalmine and discretine. All these alkaloids are described for the first time in G. olivacea and their chemotaxonomic significance was discussed. The structure elucidation of these isolated alkaloids was established by extensive analyses of 1D and 2D NMR spectroscopy in combination with MS. The NMR data for atherosperminine, argentinine, and atherosperminine N-oxide were reviewed.     

New alkaloids from Strychnos icaja

The alkaloids of Strychnos icaja (Loganiaceae) have been studied. An extract from Zaire leaf material yielded nine alkaloids, comprising novacine, the new base 21,22-α-epoxy-4,14-dihydroxy-3-methoxy-N-methyl-sec.-pseudostrychnine, and seven others of known structure previously obtained from the plant. Cameroun leaf material gave five alkaloids, of which one, 21,22-α-epoxy-3,4-dimethoxy-N-methyl-sec.-pseudostrychnine, is new. Fruits from Gabon afforded eight alkaloids; two of them are new and are formulated as 21,22-α-epoxy-4-methoxy-N-methyl-sec.-pseudostrychnine and the corresponding 14-hydroxy derivative.     

生物碱抗心律失常的作用及其分子机制

生物碱是广泛存在于生物体内尤其是天然植物中的碱性含氮有机化合物，部分生物碱具有抗心律失常、抗高血压、抗炎以及抗肿瘤等多种生理功能。心律失常是由心脏电生理活动紊乱引起的疾病，是心血管疾病高发病率和死亡率的主要原因，在世界范围内严重威胁人类生命健康。文中综述生物碱在抗心律失常中的作用和分子机制研究进展，并展望其开发应用前景。     

Erythrinoid and indol alkaloids isolated from the seeds of Erythrina rubrinervia Kunth: Chemotaxonomic significance

In the present work, we report the isolation of five alkaloids from the seeds of Erythrina rubrinervia. Four of the isolated alkaloids are erythrinoid type alkaloids which were identified as erysodine (1), erysovine (2), erythraline (3) and erysotrine (4), plus an indolic alkaloid which was identified as hypaphorine (5). The analysis of spectroscopic data for the alkaloid l-hypaphorine shows that the published structure (5a) must be revised, and the correct structure is that depicted as the structure 5c. The chemical structures were elucidated by full spectroscopic analysis. The chemotaxonomic significance of those findings in the genus Erythrina is also discussed.     

Five new alkaloids from Aconitum apetalum (Ranunculaceae)

Twenty-one alkaloids, including five new ones, acoapetaldines A–E (1–5), were isolated from the whole plants of Aconitum apetalum. Among them, 1 is an aconitine-type diterpenoid alkaloid, 2 and 3 are aporphine alkaloids and 4 and 5 are napelline-type diterpenoid alkaloids. The structures of the new alkaloids were elucidated by spectroscopic data analysis and that of acoapetaldine D (4) was confirmed by single crystal X-ray crystallography. Acoapetaldine A (1) and aconorine (12) exhibited moderate anti-tobacco mosaic virus (anti-TMV) activity, while corydine (15) displayed moderate antimicrobial activity against Pseudomonas aeruginosa.     

Quaternary alkaloids of Thalictrum foliolosum

The isolation and identification of eleven alkaloids from the quaternary alkaloid fraction of a root extract of Thalictrum foliolosum are described     

Distribution of Benzylisoquinolines in Magnoliidae and Other Taxa

Based on the analysis of benzylisoquinoline alkaloids of 323 samples in 11 families, 50 genera and 181 species of the Chinese flora discussed in this paper are the biogenesis, evolution, distribution pattern and botanical sources as well as the pharmacological action of this specific category of alkaloids. Benzylisoquinoline alkaloids are found mainly in Magnoliidae, in which aporphines, bisbenzylisoquinolines and protoberberines are the three major types of the alkaloids. More specifically, aporphines appeare more concentrated in primitive woody plants such as the Annonaceae, while bisbenzylisoquinolines are especially common in the Menispermaceae, Thalictrum (the Ranunculaceae) and Berberis (the Berberidaceae). As to protoberberines, the quaternary ones occur mainly in the families Ranunculaceae and Berberidaceae, whereas the tertiary ones mainly in the relatively advanced families Menispermaceae and Papaveraceae within Magnoliidae. As a whole, a general rule can be drawn that the simpler the chemical structure of the benzylisoquinolines is, the more widely they are distributed in primitive groups; more specific ones only have a limited distribution in more advanced groups or even within one family or one to several genera. This general pattern of distribution of benzylisoquinoline alkaloids in plants may be of value as a taxonomic criterion for plant systematics. Furthermore, this group of alkaloids covers the gamut of pharmacologic responses, such as the antibacterial effect and the effect to cardiovascular and nervous systems, and consequently the correlation between benzylisoquinoline alkaloids and their pharmacologicactivities within Magnoliidae may worthily be applied for the finding of new drugs.     

异甾体生物碱类化合物及药理活性研究进展

异甾体生物碱类结构多变,药理活性多样,主要分布于百合科贝母属和藜芦属植物中。近十五年内共报道了80个新发现的异甾体生物碱类成分,药理活性涉及抗炎、镇痛、降压、平喘、抗血栓、胆碱酯酶抑制、抗病毒和抗肿瘤等作用。本文综述了2006至2020年间该类化合物的植物来源、化学结构及药理活性,并对该类化合物的未来研究探索进行了讨论与展望。     

Biodiversity of Convolvulaceous species that contain ergot alkaloids,indole diterpene alkaloids,and swainsonine

Convolvulaceous species have been reported to contain several bioactive principles thought to be toxic to livestock including the calystegines, swainsonine, ergot alkaloids, and indole diterpene alkaloids. Swainsonine, ergot alkaloids, and indole diterpene alkaloids are produced by seed transmitted fungal symbionts associated with their respective plant host, while the calystegines are produced by the plant. To date, Ipomoea asarifolia and Ipomoea muelleri represent the only Ipomoea species and members of the Convolvulaceae known to contain indole diterpene alkaloids, however several other Convolvulaceous species are reported to contain ergot alkaloids. To further explore the biodiversity of species that may contain indole diterpenes, we analyzed several Convolvulaceous species (n = 30) for indole diterpene alkaloids, representing four genera, Argyreia, Ipomoea, Stictocardia, and Turbina, that had been previously reported to contain ergot alkaloids. These species were also verified to contain ergot alkaloids and subsequently analyzed for swainsonine. Ergot alkaloids were detected in 18 species representing all four genera screened, indole diterpenes were detected in two Argyreia species and eight Ipomoea species of the 18 that contained ergot alkaloids, and swainsonine was detected in two Ipomoea species. The data suggest a strong association exists between the relationship of the Periglandula species associated with each host and the occurrence of the ergot alkaloids and/or the indole diterpenes reported here. Likewise there appears to be an association between the occurrence of the respective bioactive principle and the genetic relatedness of the respective host plant species.     

Alkaloids of turkish papaver tauricola

The major alkaloids of Papaver tauricola collected in three different parts of Anatolia have proved to be of the rhoeadine type. The three collections possessed different major alkaloids and the existence of chemical strains containing rhoeadine-type alkaloids, is indicated. In addition to the rhoeadine-type alkaloids (rhoeagenine, rhoeadine, oreogenine, oreodine, glaucamine, glaudine and epiglaudine), tetrahydroprotoberberine-(sinactine, scoulerine) and isopavine- (amurensinine) type alkaloids have been isolated as minor products. These findings contrast with the previous literature in which 1-benzyltetrahydroisoquinoline- and proaporphine types were reported to be the major alkaloids.     

Pyrrolizidine alkaloids and other constituents from Emilia fosbergii Nicolson

Emilia fosbergii is a member of the tribe Senecioneae (Asteraceae), most species of which contain pyrrolizidine alkaloids. Notwithstanding, the phytochemistry of E. fosbergii is poorly understood, and pyrrolizidine alkaloids produced by this species have yet to be characterized. In this work, the presence of 11 pyrrolizidine alkaloids, three caffeoylquinic acid derivatives, and six flavonoids were detected by liquid chromatography coupled to high-resolution mass spectrometry analyses. Pyrrolizidine alkaloids of otonecine, retronecine, and platynecine bases are annotated in different parts of the plant. Furthermore, emiline was isolated, possibly indicating that E. fosbergii has a close phylogenetic relationship with E. coccinea. The chemophenetic implications of the presence of pyrrolizidine alkaloids in E. fosbergii and tribe Senecioneae are discussed.     

Kokusaginine and evolitrine from Acronychia pedunculata

Kokusaginine and evolitrine are the major alkaloids present in Sri Lankan Acronychia pedunculata. The Indian variety of Acronychia laurifolia collected in Madras does not contain these alkaloids.     

Induction of apoptosis in a human erythroleukemic cell line K562 by Tylophora alkaloids involves release of cytochrome c and activation of caspase 3

Tylophora alkaloids are plant products known for their antiasthamatic and antiproliferative activities. The underlying cellular changes resulting from inhibition of proliferation were investigated. Tylophora alkaloids induced apoptosis in K562 cells with characteristic apoptotic features like nuclear condensation, apoptotic body formation, flipping of membrane phosphatidylserine, activation of caspase 3 and release of mitochondrial cytochrome c. These studies suggest that the Tylophora alkaloids, in addition to their antiproliferative effects also induce apoptosis in erythroleukemic cells. These observations imply that Tylophora alkaloids could be useful molecules for their antiproliferative activity and for induction of apoptosis in tumor cells.     

Norditerpene and diterpene alkaloids from Aconitum variegatum

Aerial parts of Aconitum variegatum L. from the Pyrenees furnished four norditerpene alkaloids, 16 beta-hydroxycardiopetaline, 8-ethoxysachaconitine, 14-acetylgenicunine B, N-deethyl-N-19-didehydrosachaconitine, five diterpene alkaloids 15-veratroyldictizine, 15-veratroyl-17-acetyldictizine, 15-veratroyl-17-acetyl-19-oxodictizine, N-ethyl-1 alpha-hydroxy-17-veratroyldictizine, variegatine and the known alkaloids sachaconitine, 14-O-acetylsachaconitine, karakoline, talatizamine, 10-hydroxytalatizamine, 14-acetyltalatizamine, 14-acetyl-10-hydroxytalatizamine, N-methylarmepavine, pengshenin B, delsoline, dihydrodelsoline, delcosine and genicunin B. Structures of the alkaloids were established by MS, 1D- and 2D-NMR techniques.     

禾草内生真菌生物碱的研究进展

综述了国内外近20a以来在禾草内生真菌生物碱方面的研究进展。目前,已发现至少4大类10余种生物碱与内生真菌有关。各类生物碱中典型代表物的分子结构已完全清楚,部分内生真菌在离体条件下可产生除黑麦草碱外的生物碱,但产碱量较其在植物体中所产生的低很多,可相差150余倍之多。随着生物技术的发展,美国、新西兰等国在波胺、麦角碱和loline的生物合成途径方面已有了初步的进展,对个别具有重要功能基因以及其所编码的酶已有了深入研究。各种生物碱的致毒机理尚未完全清楚,除饱和吡咯化合物为新陈代谢类毒素和神经性毒素外,其余3类生物碱均为神经性毒素。生物碱可增加禾草对40余种害虫的抗性,并可增加对某些线虫和病害的抗性。诸多因素均可影响寄主植株中生物碱的种类和浓度,包括寄主植株：种群和生态型,植物品种和基因型,植株的部位和生长期;环境：气候因素,土壤养分,季节和年度变化;内生真菌菌株和草地管理利用方式等。用于生物碱检测的主要方法为预分离检测法和直接检测法,其中高效液相色谱法以其分离能力强、选择性高、测定灵敏度高,操作简单,可在室温下进行,应用范围极广的优点而广泛应用。目前,国际关于禾草内生真菌生物碱研究的重点包括创造不含对家畜有毒素的有益禾草-内生真菌共生体,开展基因工程研究以及合理利用生物碱,使其成为新一代的“生物农药”。     

Pregnane alkaloids from Sarcococca ruscifolia and their cytotoxic activity

Six pregnane alkaloids were isolated from the root of Sarcococca ruscifolia. The structures of three new alkaloids, namely, sarcorucinine E–G (1–3), were elucidated using spectroscopic methods, while three known alkaloids, namely, epipachysamine D, pachysamine M, and sarcovagine D, were identified by comparing their spectral data with those of the compounds reported earlier. All compounds were evaluated for their inhibitory activities against multiple types of cancer cells.     

Alkaloid profiles of Dermatophyllum arizonicum,Dermatophyllum gypsophilum,Dermatophyllum secundiflorum,Styphnolobium affine,and Styphnolobium japonicum previously classified as Sophora species

Sophora arizonica, Sophora gypsophila, Sophora secundiflora, Sophora affinis, and Sophora japonica were recently reclassified as Dermatophyllum arizonicum, Dermatophyllum gypsophilum, Dermatophyllum secundiflorum, Styphnolobium affine, and Styphnolobium japonicum, respectively. Some legumes of the sub family Papilionoideae including Sophora species are reported to contain a variety of quinolizidine alkaloids. The quinolizidine alkaloid profiles of D. arizonicum, D. gypsophilum, D. secundiflorum, S. affine, and S. japonicum were investigated qualitatively and quantitatively using field collections and herbarium specimens throughout their range of geographical distribution for the native species. This is the first report of the alkaloid profiles of D. arizonicum and D. gypsophilum. Alkaloid profiles of the other species were compared to previous reports. The Dermatophyllum species contain quinolizidine alkaloids, and the teratogen anagyrine (11), while the Styphnolobium species do not contain quinolizidine alkaloids. The chemotaxonomic data are consistent with the reclassification of each species.     

托烷类生物碱生物合成机理及其生物工程研究进展

托烷类生物碱主要包括阿托品、莨菪碱、山莨菪碱、东莨菪碱和樟柳碱,是主要抗胆碱类药物。解析药用茄科植物托烷类生物碱合成的分子调控机制以及研发高产托烷类生物碱的植物生物反应器一直是近几年的研究热点。该文对近年来国内外有关托烷类生物碱在不同茄科植物中的合成部位、分子调控和利用转基因技术研发高产托烷类生物碱的发根生物反应器的研究进展进行综述,并对可能存在的问题以及应用前景进行了展望。     

Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants

Alkaloids represent a large and diverse group of compounds that are related by the occurrence of a nitrogen atom within a heterocyclic backbone. Unlike other types of secondary metabolites, the various structural categories of alkaloids are unrelated in terms of biosynthesis and evolution. Although the biology of each group is unique, common patterns have become apparent. Opium poppy ( Papaver somniferum ), which produces several benzylisoquinoline alkaloids, and Madagascar periwinkle ( Catharanthus roseus ), which accumulates an array of monoterpenoid indole alkaloids, have emerged as the premier organisms used to study plant alkaloid metabolism. The status of these species as model systems results from decades of research on the chemistry, enzymology and molecular biology responsible for the biosynthesis of valuable pharmaceutical alkaloids. Opium poppy remains the only commercial source for morphine, codeine and semi-synthetic analgesics, such as oxycodone, derived from thebaine. Catharanthus roseus is the only source for the anti-cancer drugs vinblastine and vincristine. Impressive collections of cDNAs encoding biosynthetic enzymes and regulatory proteins involved in the formation of benzylisoquinoline and monoterpenoid indole alkaloids are now available, and the rate of gene discovery has accelerated with the application of genomics. Such tools have allowed the establishment of models that describe the complex cell biology of alkaloid metabolism in these important medicinal plants. A suite of biotechnological resources, including genetic transformation protocols, has allowed the application of metabolic engineering to modify the alkaloid content of these and related species. An overview of recent progress on benzylisoquinoline and monoterpenoid indole alkaloid biosynthesis in opium poppy and C. roseus is presented.