Aconitum Species Research Articles

Anatomy of stem‐node‐leaf continuum in Aconitum (Ranunculaceae) in the Eastern Carpathians

Studies of the anatomical structure of the stem and leaf, with special emphasis on the organization of the vascular system, has been carried out on 13 Aconitum species from Aconitum subgenera Aconitum, Anthora and Lycoctonum. All investigated species show a more or less mesomorphic anatomical structure, typical for other Ranunculaceae. Hence, these species have similar trilacunar three‐trace organization of the nodal vascular system. In the stem the vascular system is open (with weakly developed cambium) or closed collateral, and incomplete (consisting of the bundles were represented), large complete, middle‐size complete and small incomplete or with weakly developed xylem. The number of vascular bundles in petioles appear to have no taxonomical value. Nevertheless, it was found that the spatial organization of these vascular bundles in the petiole are of taxonomic importance. As a result, the investigated species can be divided into four main groups congruent with the current sectional and subgeneric division of the genus. The only exception was A. × cammarum (A. sect. Acomarum) in which the is identical to that of A. sect. Cammarum. The most primitive vascularization is found in A. anthora, while the most advanced one is found in A. variegatum. The highly differentiated and distinct nodal anatomy of A. anthora suggests a high, plausibly subgeneric, taxonomical rank of this species.

Clinical Aspects of Aconitum Preparations.

Aconite species have played an important role in human history. Aconitum species have been used worldwide as poisons as well as remedies. Their potential in targeting several ailments such as pain, rheumatism, and lethargy has been recognized by Western, Chinese, and Indian health care practitioners. Aconite use in herbal preparations has declined, especially in Europe and the United States, in the first half of the twentieth century due to several reported toxicity cases. The situation has changed with the application of new technologies for the accurate analysis of its toxic components and the development of efficient detoxification protocols. Some Asian countries started small clinical trials to evaluate the potency and safety of different marketed aconite preparations. The current review summarizes therapeutic uses of aconite preparations in China, Taiwan, India, and Japan. It also highlights clinical trial results with special emphasis on their limitations. Modern drugs and pharmacopoeial preparations derived from aconite are also discussed.

Discovery of characteristic chemical markers for classification of aconite herbs by chromatographic profile and probabilistic neural network

Most Aconitum species, also known as aconite, are extremely poisonous, so it must be identified carefully. Differentiation of Aconitum species is challenging because of their similar appearance and chemical components. In this study, a universal strategy to discover chemical markers was developed for effective authentication of three commonly used aconite roots. The major procedures include: (1) chemical profiling and structural assignment of herbs by liquid chromatography with mass spectrometry (LC-MS), (2) quantification of major components by LC-MS, (3) probabilistic neural network (PNN) model to calculate contributions of components toward species classification, (4) discovery of minimized number of chemical markers for quality control. The MS fragmentation pathways of diester-, monoester-, and alkyloyamine-diterpenoid alkaloids were compared. Using these rules, 42 aconite alkaloids were identified in aconite roots. Subsequently, 11 characteristic compounds were quantified. A component–species modeling by PNN was then established combining the 11 analytes and 26-batch samples from three aconite species. The contribution of each analyte to species classification was calculated. Selection of fuziline, benzoylhypaconine, and talatizamine, or a combination of more compounds based on a contribution order, can be used for successful categorization of the three aconite species. Collectively, the proposed strategy is beneficial to selection of rational chemical markers for the species classification and quality control of herbal medicines.

Identification of four Aconitum species used as "Caowu" in herbal markets by 3D reconstruction and microstructural comparison.

Authentication is the first priority when evaluating the quality of Chinese herbal medicines, particularly highly toxic medicines. The most commonly used authentication methods are morphological identification and microscopic identification. Unfortunately, these methods could not effectively evaluate some herbs with complex interior structures, such as root of Aconitum species with a circular conical shape and an interior structure with successive changes. Defining the part that should be selected as the standard plays an essential role in accurate microscopic identification. In this study, we first present a visual 3D model of Aconitum carmichaeli Debx. constructed obtained from microscopic analysis of serial sections. Based on this model, we concluded that the point of largest root diameter should be used as the standard for comparison and identification. The interior structure at this point is reproducible and its shape and appearance can easily be used to distinguish among species. We also report details of the interior structures of parts not shown in the 3D model, such as stone cells and cortical thickness. To demonstrate the usefulness of the results from the 3D model, we have distinguished the microscopic structures, at their largest segments, of the other three Aconitum species used for local habitat species of Caowu. This work provides the basis for resolution of some debate regarding the microstructural differences among these species. Thus, we conclude that the 3D model composed of serial sections has enabled the selection of a standard cross-section that will enable the accurate identification of Aconitum species in Chinese medicine.

The influences of aconitine, an active/toxic alkaloid from aconitum, on the oral pharmacokinetics of CYP3A probe drug buspirone in rats.

Aconitine (AC), an active/toxic alkaloid from Aconitum species, is commonly present in Traditional Chinese Medicine (TCM) prescriptions because of the great effectiveness of Aconitum for the treatment of rheumatoid arthritis, cardiovascular diseases, and tumors in clinic. Buspirone (BP) is a sensitive CYP3A probe drug that is administered through oral/intravenous routes as recommended by the U.S. Food and Drug Administration. This study aims to investigate the influences of AC (0.125 mg/kg, oral) on first-pass (intestinal and hepatic) CYP3A activity by using oral BP as the probe in rats. The pharmacokinetics of oral buspirone hydrochloride at different doses (12.5, 25, and 50 mg/kg) were conducted. The pharmacokinetics of oral BP in rats pretreated with single dose or multiple doses (7-day) of AC were investigated. The plasma concentrations of BP and its major metabolites [1-(2-pyrimidinyl)piperazine (1-PP) and 6'-hydroxybuspirone (6'-OH-BP)] were determined. The formation ratios of 1-PP and 6'-OH-BP from BP (AUC0-∞ of 1-PP/AUC0-∞ of BP and AUC0-∞ of 6'-OH-BP/AUC0-∞ of BP values) showed no alternation when the dose of BP changed. Single dose of AC decreased the AUC0-∞ of BP by 53% but increased the formation ratio of 6'-OH-BP by 74% (P<0.05). Multiple AC exposure increased the AUC0-∞ of BP by 110%, and the formation ratios of 1-PP and 6'-OH-BP from BP were increased by 229% and decreased by 95%, respectively (P<0.05). Conclusively, single/multiple AC exposure did not alter the first-pass CYP3A activity when using oral BP as probe in rats. Nevertheless, multiple AC exposure had markedly changed the production of BP metabolites.

In vivo and in vitro metabolites from the main diester and monoester diterpenoid alkaloids in a traditional chinese herb, the aconitum species.

Diester diterpenoid alkaloids (DDAs), such as aconitine (AC), mesaconitine (MA), and hypaconitine (HA), are both pharmacologically active compounds and toxic ingredients in a traditional Chinese herb, the Aconitum species. Many DDA metabolism studies have been performed to explore mechanisms for reducing toxicity in these compounds and in Aconitum species extracts for safe clinical administration. In this review, we summarize recent progress on the metabolism of toxic AC, MA, and HA and corresponding monoester diterpenoid alkaloids (MDAs) in the gastrointestinal tract and liver in different animal species and humans in vivo and/or in vitro, where these alkaloids are primarily metabolized by cytochrome P450 enzymes, carboxylesterases, and intestinal bacteria, which produces phase I metabolites, ester hydrolysed products, and lipoalkaloids. Furthermore, we classify metabolites detected in the blood and urine, where the aforementioned metabolites are absorbed and excreted. Less toxic MDAs and nontoxic alcohol amines are the primary DDA metabolites detected in the blood. Most other DDAs metabolites produced in the intestine and liver detected in the urine have not been reported in the blood. We propose an explanation for this nonconformity. Finally, taking AC, for instance, we generalize a process of toxicity reduction in the body after oral AC administration for the first time.

AFLP analysis reveals infraspecific phylogenetic relationships and population genetic structure of two species of Aconitum in Central Europe

The genetic diversity of two &lt;em&gt;Aconitum&lt;/em&gt; species endemic to the Carpathian Mountains and Sudetes was studied. A reticulate evolution between them was earlier postulated as an effect of secondary contact. The genetic diversity at the individual and taxonomic levels was examined across the entire geographical ranges of the taxa in 11 populations based on 247 AFLP markers found in 112 individuals in the Sudetes and Western Carpathians. The overall genetic differentiation was greater within the Sudetic &lt;em&gt;A. plicatum&lt;/em&gt; (&lt;em&gt;F&lt;/em&gt;&lt;span&gt;&lt;sub&gt;ST&lt;/sub&gt;&lt;/span&gt; = 0.139, &lt;em&gt;P&lt;/em&gt; &amp;lt; 0.001) than within the Carpathian &lt;em&gt;A. firmum&lt;/em&gt; (&lt;em&gt;F&lt;/em&gt;&lt;span&gt;&lt;sub&gt;ST&lt;/sub&gt;&lt;/span&gt; = 0.062, &lt;em&gt;P&lt;/em&gt; &amp;lt; 0.001), presumably due to the long-lasting geographic isolation between the Giant Mts and Praděd (Sudetes) populations of the species. Interestingly, relatively distant and presently isolated populations of &lt;em&gt;A. plicatum&lt;/em&gt; and &lt;em&gt;A. f.&lt;/em&gt; subsp. &lt;em&gt;maninense&lt;/em&gt; share a part of their genomes. It could be an effect of their common evolutionary history, including past and present reticulations. The introgression among infraspecific taxa of &lt;em&gt;Aconitum&lt;/em&gt; is common, probably as a result of seed dispersal within a distance of ca. 20 km (Mantel’s &lt;em&gt;r&lt;/em&gt; = 0.36, &lt;em&gt;P&lt;/em&gt; = 0.01). &lt;em&gt;Aconitum f.&lt;/em&gt; subsp. &lt;em&gt;maninense&lt;/em&gt; had the highest genetic diversity indices: Nei’s &lt;em&gt;h&lt;/em&gt; and rarefied &lt;em&gt;FAr&lt;/em&gt;, and divergence index &lt;em&gt;DW&lt;/em&gt; (&lt;em&gt;P&lt;/em&gt; ≤ 0.05), pointing to its presumably ancient age and long-term isolation.

Studies on Vegetative and Reproductive Ecology of Paris polyphylla Smith: A Vulnerable Medicinal Plant

Paris polyphylla Smith is an important medicinal plant that is considered vulnerable in many parts of the world. The species exhibits poor adaptability to changed environment and susceptible to climatic conditions for reproductive vigor. During the present study the species was studied in four different natural niches as well as synthetic habitats to check the adaptability to artificial conditions, its morphological and physiological characters and its interaction in its community so that conservation strategies could be worked out. The present study indicates that P. polyphylla exhibits healthy growth as well as reproduction in undisturbed area with canopy covers over 80%. The plant grows in well-drained rich humus soil and grows well with certain key associated species such as Quercus species, Taxus baccata, Aconitum species, Eupatorium adenophorum, Smilax species etc. Many plants were non-flowering and more than 60% were found non-flowering in its habitat during its flowering season in any particular year. There are clear morphological changes as the flowers stages from pre-fertilization to post-fertilization. Arrangement of anthers in two whorls shows a distinct and unique floral display. Light is an important factor during seed setting and less than 50% shade lowers the seed productivity very significantly. Predators such as slugs and snails are found on the plant. Urgent conservation and new innovative ways are necessary to propagate this economically important plant to ensure its continuity.

Paper chromatography of anthocyanins in two species of Aconitum from the Tatry .Mts.: A. variegatum (L.) Rchb., and A. napellus ssp. skerisorae (Gayer) Seitz.

The results of studies on phenolic compounds occurence and variation in the two Aconitum species were reported in our previous paper (Szweykowski, Krzakowa, 1977a and b). A modified extraction method allowed us to get additional data on anthocyanin variation in flowers of the same species. In addition one albino plant of&lt;i&gt; A. variegatum&lt;/i&gt; was also investigated in this respect.

Śodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants.

Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Śodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanābha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, β–asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Śodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process.

Phytochemical and pharmacological research on Chinese and European Aconitum species

Phytochemical and pharmacological research on Chinese and European Aconitum species

Aconitum alkaloid poisoning related to the culinary uses of aconite roots.

Aconite roots (roots or root tubers of the Aconitum species) are eaten as root vegetables and used to prepare herbal soups and meals, mainly for their purported health benefits. Aconite roots contain aconitine and other Aconitum alkaloids, which are well known cardiotoxins and neurotoxins. To better understand why Aconitum alkaloid poisoning related to the culinary uses of aconite roots can occur and characterize the risks posed by these “food supplements”, relevant published reports were reviewed. From 1995 to 2013, there were eight reports of aconite poisoning after consumption of these herbal soups and meals, including two reports of large clusters of cases (n = 19–45) and two reports of cases (n = 15–156) managed by two hospitals over a period of 4.5 to 5 years. The herbal formulae used did not adhere to the suggested guidelines, with regarding to the doses (50–500 g instead of 3–30 g per person) and types (raw instead of processed) of aconite roots used. The quantities of Aconitum alkaloids involved were huge, taking into consideration the doses of aconite roots used to prepare herbal soups/meals and the amounts of aconite roots and herbal soups/meals consumed. In a large cluster of cases, despite simmering raw “caowu” (the root tuber of A. kusnezoffii) in pork broth for 24 h, all 19 family members who consumed this soup and boiled “caowu” developed poisoning. Severe or even fatal aconite poisoning can occur after consumption of herbal soups and foods prepared from aconite roots. Even prolonged boiling may not be protective if raw preparations and large quantities of aconite roots are used. The public should be warned of the risk of severe poisoning related to the culinary and traditional medicinal uses of aconite roots.

Distribution of toxic alkaloids in tissues from three herbal medicine Aconitum species using laser micro-dissection, UHPLC–QTOF MS and LC–MS/MS techniques

Aconite poisoning continues to be a major type of poisoning caused by herbal drugs in many countries. Nevertheless, despite its toxic characteristics, aconite is used because of its valuable therapeutic benefits.The aim of the present study was to determine the distribution of toxic alkaloids in tissues of aconite roots through chemical profiling. Three species were studied, all being used in traditional Chinese Medicine (TCM) and traditional Indian medicine (Ayurveda), namely: Aconitum carmichaelii, Aconitum kusnezoffii and Aconitum heterophyllum.Laser micro-dissection was used for isolation of target microscopic tissues, such as the metaderm, cortex, xylem, pith, and phloem, with ultra-high performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC–QTOF MS) employed for detection of metabolites. Using a multi-targeted approach through auto and targeted LC–MS/MS, 48 known compounds were identified and the presence of aconitine, mesaconitine and hypaconitine that are the biomarkers of this plant was confirmed in the tissues. These results suggest that the three selected toxic alkaloids were exclusively found in A. carmichaelii and A. kusnezoffii. The most toxic components were found in large A. carmichaelii roots with more lateral root projections, and specifically in the metaderm, cork and vascular bundle tissues. The results from metabolite profiling were correlated with morphological features to predict the tissue specific distribution of toxic components and toxicity differences among the selected species. By careful exclusion of tissues having toxic diester diterpenoid alkaloids, the beneficial effects of aconite can still be retained and the frequency of toxicity occurrences can be greatly reduced.Knowledge of tissue-specific metabolite distribution can guide users and herbal drug manufacturers in prudent selection of relatively safer and therapeutically more effective parts of the root. The information provided from this study can contribute towards improved and effective management of therapeutically important, nonetheless, toxic drug such as Aconite.

Nectar production and carbohydrate composition across floral sexual phases: contrasting patterns in two protandrous Aconitum species (Delphinieae, Ranunculaceae)

In dichogamous species, it is necessary that pollinators are attracted both to male- and female-phase flowers in order to achieve effective cross-pollination. We investigated, over a two-year period, how nectar production and composition differs in protandrous flowers of Aconitum lycoctonum L. and Aconitum carmichaelii Debeaux, two species originating from different geographical regions. Flowers of A. carmichaelii secreted approx. 2.5-fold more nectar than flowers of A. lycoctonum. The nectar of A. carmichaelii was sucrose-dominant (87.6:9.5:2.9, sucrose:fructose:glucose), whereas sucrose-rich nectar, lacking glucose, occurred in A. lycoctonum (39.9:60.1, sucrose:fructose). Total sugar concentration was similar (53%, on average) in both species. These species also showed contrasting patterns in nectar production and composition between the floral sexual phases. On average, in A. carmichaelii, male-phase flowers produced 2.4-fold more nectar than female-phase flowers in the two years of study, and nectar was sucrose-dominant, irrespective of sexual phase. By contrast, nectar production in A. lycoctonum was biased towards the male phase in one year of study and towards the female phase in the other, and whereas nectar was sucrose-dominant during the male-phase, it was fructose-rich during the female phase, indicating sucrose re-absorption. Although the characteristics of nectar in these Aconitum species indicate pollination by bumblebees, it is possible that their biogeographical history, and not pollinator selection alone, is important in understanding the lack of glucose in A. lycoctonum nectar. Variability in nectar production and/or carbohydrate composition between sexual phases suggests indirectly that nectar traits complement each of the latter. Nevertheless, further research is required if we are to understand the significance of these disparities in pollination ecology, i.e. for promoting pollinator movements between flowers and plants in order to achieve cross-pollination and avoid inbreeding.

The antidiarrheal and C19/C20 diterpenoid alkaloid constituents of high altitude Himalayan Aconitum heterophyllum

The plants of Aconitum genus are natives of cold region wherever found in the world. In India, these plants are found to grow in the high altitudes of Himalayan region above 10,000ft to snow lines. These plants are of great interest because of their pharmacological importance. Extracts of Aconitum species are being used all over the world for the treatment of hypertension, neuralgia, rheumatism and arthritis. Aconitum heterophyllum Wall known as Atis, Atibisha is a highly prized Himalayan herb being used since ages in Indian Systems of medicine (ISM) as febrifuge, bitter tonic especially in combating debility after malaria and other fevers. It is specially efficacious for the treatment of diarrea, dysentery, cough, dyspepsia and chronic enteritis.

English

Alpine and subalpine regions of Kumaun Himalaya were surveyed qualitatively and quantitatively for the population study to determine the status of Aconitum ferox and A. heterophyllum. Low population density across the surveyed populations and restricted distribution to specific pockets indicates poor availability of the species in the study area. Illegal and over exploitation of these species pose threat to their existence. The present study clarifies the population structure of identified aconite species in Kumaun Himalaya. Observations reveal that on the basis of six attributes (that is habitat preference, distribution range, population size, use pattern, extraction trend, native and endemic species) used to assign threat categories, both the Aconitum species are endangered. Key words: Endangered, Himalaya, Aconitum heterophyllum, Aconitum ferox, medicinal plant.

A case report of cardiotoxicity due to homeopathic drug overdose

Aconite is one of the most toxic plants. Aconitine and related alkaloids found in the Aconitum species are highly toxic cardiotoxins and neurotoxins. Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots. The toxic components of Aconitum as aconitine and related alkaloids cause cardiotoxicity, neurotoxicity and gastrointestinal toxicity through their actions on sodium channels. Cardiac manifestations include hypotension and ventricular tachyarrhythmias. Ventricular tachyarrhythmias and refractory cardiovascular collapse, such as in the case of this patient account for lifethreatening toxicities in severe aconite poisoning. In general, vagal slowing is seen in 10 to 20% of fatal intoxications. If higher concentrations are present, supraventricular tachycardia, ventricular tachycardia, torsades de pointes, and other conduction disturbances may be seen. Ventricular fibrillation may be seen, and is often the cause of death. Available clinical evidence suggests that drugs like amiodarone and flecainide are reasonable firstline treatment.

Flowering, pollen production and insect visitation in two Aconitum species (Ranunculaceae)

Flowering phenology, diurnal dynamics of blooming, insect visitation and pollen production in &lt;em&gt;Aconitum lycoctonum &lt;/em&gt;L. and &lt;em&gt;Aconitum carmichaelii &lt;/em&gt;Debeaux were investigated in 2012–2013 in the Lublin area, SE Poland. Flowering of &lt;em&gt;A. lycoctonum &lt;/em&gt;occurred in June/July, whereas &lt;em&gt;A. carmichaelii &lt;/em&gt;bloomed in September/October. Both &lt;em&gt;Aconitum &lt;/em&gt;species differed in terms of the diurnal pattern of flowering. The flowers of &lt;em&gt;A. lycoctonum &lt;/em&gt;started opening at 5.00, whereas those of &lt;em&gt;A. carmichaelii &lt;/em&gt;started blooming at 8.00 (GMT+2h). The species differed in the number of anthers per flower, the size of anthers, and the mass of pollen produced in anthers. As a result, the flowers of &lt;em&gt;A. lycoctonum &lt;/em&gt;produced less pollen (mean = 1.0 mg per 10 flowers) than the flowers of &lt;em&gt;A. carmichaelii &lt;/em&gt;(mean = 8.2 mg per 10 flowers). The estimated pollen yield was 0.2 g per m&lt;sup&gt;2&lt;/sup&gt; for &lt;em&gt;A. lycoctonum &lt;/em&gt;and 1.6 g per m&lt;sup&gt;2&lt;/sup&gt; for &lt;em&gt;A. carmichaelii&lt;/em&gt;. The flowers of both &lt;em&gt;Aconitum &lt;/em&gt;species were foraged exclusively by bumblebees with the predominance of the long-tongued &lt;em&gt;Bombus hortorum&lt;/em&gt;. Nectar was a more attractive floral reward than pollen. The propagation of &lt;em&gt;Aconitum lycoctonum &lt;/em&gt;and &lt;em&gt;A. carmichaelii&lt;/em&gt; in ornamental gardens may support the conservation of bumblebees whose populations are steadily declining.

Aconitum qianxiense,a New Speceis of Ranunculaceae from Hebei

A species of the genus Aconitum(Ranunculaceae),Aconitum qianxiense,is described as new from Hebei Province.In shape of leaves and flower it bears obvious resemblance to A.carmichaeli Debx.,and from the latter differs in its bifurcate tubers,humile zigzag glabrous stem,smaller glabrous leaves,solitary terminal flower,and glabrous pedicel,outer surfaces of sepals and carpels.

Gymnaconitum, a new genus of Ranunculaceae endemic to the Qinghai–Tibetan Plateau

AbstractThe monophyly of traditional Aconitum remains unresolved, owing to the controversial systematic position and taxonomic treatment of the monotypic, Qinghai–Tibetan Plateau endemic A. subg. Gymnaconitum. In this study, we analyzed two datasets using maximum likelihood and Bayesian inference methods: (1) two markers (ITS, trnL–F) of 285 Delphinieae species, and (2) six markers (ITS, trnL–F, trnH–psbA, trnK–matK, trnS–trnG, rbcL) of 32 Delphinieae species. All our analyses show that traditional Aconitum is not monophyletic and that subgenus Gymnaconitum and a broadly defined Delphinium form a clade. The SOWH tests also reject the inclusion of subgenus Gymnaconitum in traditional Aconitum. Subgenus Gymnaconitum markedly differs from other species of Aconitum and other genera of tribe Delphinieae in many non–molecular characters. By integrating lines of evidence from molecular phylogeny, divergence times, morphology, and karyology, we raise the monotypic A. subg. Gymnaconitum to generic status.