Aconite Root Research Articles

Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products

The antinociceptive effects of crude Fuzei, the root of Aconitum carmichaeli and of Fuzei processed by three different methods were determined in mice and rats using the light tail-flick assay. A dose-dependent and significant increase in pain threshold was found at 60 min post treatment, with doses of 20–60 mg/kg crude Fuzei. The analgesic effects of processed Fuzei (20–60 mg/kg) exhibited a dose-dependent inhibition of tail-flick, but the effects were lower than those produced by crude Fuzei in the same tests. The analgesic effect of Yan-Fuzei, the salt baking product, was the most potent of the processed products and was nearly that provided by crude Fuzei. Although the concentrations of aconitine were significantly lower in the processed Fuzei than in the crude Fuzei, a higher oral LD 50 was found for all of the processed Fuzei formulations. Moreover, antinociception of crude Fuzei and its processed products was attenuated but not totally blocked by naloxone at doses sufficient to block opioid μ-receptors. Furthermore, the analgesic effect of crude Fuzei and its processed products was decreased in opioid μ-receptor knockout mice, but the effect remained unaltered in mice with opioid μ-receptors, indicating that the analgesic effect of Fuzei is centrally mediated. These results demonstrate that Fuzei processed by salt baking possesses analgesic effects within a large therapeutic range, probably via a mechanism involving central opioid receptors that mediate the antinociception.

A Multidisciplinary Approach to the Toxicologic Problems Associated with the Use of Herbal Medicines

In Hong Kong, a multidisciplinary team consisting of a pharmacist, a chemical pathologist, a scientific officer, and a physician has jointly provided an advisory service on herbal safety to healthcare professionals of all public hospitals since August 2000. This paper reports the first 2 years of experience of this team to emphasize the importance of a multidisciplinary approach to herbal poisoning. Twenty referrals received from the public hospitals from August 2000 to June 2002 were reviewed. The diagnosis of herbal toxicity was made after consideration of the temporal relationship between exposure to the herb and the occurrence of the adverse event and the exclusion of other causes. The causal relationship was seen as much stronger if the herb's pharmacological effects could fully explain the adverse event, if there were similar previous reports, and if the toxicological analysis findings were supportive. In 10 patients, the adverse events were deemed unlikely to be related to the use of herbal medicines. In 3 patients, it was concluded that the adverse events were possibly related to the use of herbal medicines. In 7 patients, the causal relationship was seen to be much stronger because the adverse events in these patients simply reflected the pharmacological effects of the herbs consumed and specific toxic ingredients were isolated from herbal residues and patients' urine or serum. The clinical problems arising from the use of herbal medicines included the Aristolochia species causing acute renal failure (n = 1), aconite roots causing aconitine poisoning (n = 2), the Datura species causing anticholinergic poisoning (n = 1), and "yulan" (Stephania sinica) causing tetrahydropalmatine poisoning (n = 3). The 4 patients with acute renal failure and tetrahydropalmatine poisoning received these toxic herbs, which were not listed in the prescriptions, as a result of poor dispensing practice or for other reasons. Toxicological problems associated with the use of herbal medicines are complex and may be easily overlooked. A multidisciplinary team of experts should be made available to provide advice to frontline healthcare professionals.

Determination of Arsenic and Mercury in Chinese Medicinal Herbs by Atomic Fluorescence Spectrometry with Closed‐Vessel Microwave Digestion

A simple method was developed for the determination of trace arsenic and mercury in Chinese medicinal herbs. The samples were digested in closed‐Teflon vessels in a microwave oven, and followed with hydride generation atomic fluorescence spectrometric measurements. The experimental conditions for the digestion were carefully optimized using an orthogonal design. The accuracy of the method was validated by recovery experiments, and the analytical results for arsenic in seven medicinal herbs (Codonopsis pilosula, Radix angelicae sinensis, Aconitum carmichaeli debx, crude aconite root, giant typhonium rhizome, Rhizoma typhonii, and Radix aconiti lateralis preparata) were found to agree well with those by inductively coupled plasma atomic emission spectrometry (ICP‐AES). The linear dynamic range of the calibration curve was in the range of 0.1–400 ng/mL for arsenic, and the correlation coefficient was better than 0.999. The limit of detection was 0.1 ng/mL for arsenic. For mercury, the determination was accomplished through mercury cold vapor generation in the same instrumental system. The linear dynamic range was 0.03–250 ng/mL, with a limit of detection of 0.03 ng/mL for mercury. This was a rapid, convenient, precise, and cost‐effective method.

Clinical features and management of herb-induced aconitine poisoning

Study objective We define the potential sources, clinical manifestations, and treatment of aconitine poisoning. Methods The database of the National Poison Center in Taiwan was retrospectively searched for the diagnosis of aconitine poisoning for 1990 to 1999. The reasons for taking the aconite roots, the clinical features, management, and possible predisposing factors were noted. Results A total of 17 cases occurred and consisted of 9 men and 8 women aged 30 to 70 years. Thirteen patients ingested aconite roots as treatment for rheumatism and wounds. Two patients volunteered to test the effects of aconite roots in a drug study. Two patients accidentally ingested the aconite roots. After a latent period of 10 to 90 minutes, patients developed a combination of neurologic (n=17), cardiovascular (n=14), gastrointestinal (n=9), and other (n=5) features typical of aconitine poisoning. Four patients developed ventricular tachycardia. All patients received supportive treatment. Patients with ventricular tachycardia were also treated with charcoal hemoperfusion. All patients made a complete recovery. Conclusion Life-threatening ventricular tachycardia can occur after the consumption of aconite roots. The risk is higher with inadequately processed aconite roots, large doses, or tincture preparations. With increasing popularity of herbal medicines, herb-induced aconitine poisoning may also be seen in Western countries.

The local anesthetic activity of Aconitum alkaloids can be explained by their structural properties: a QSAR analysis.

Alkaloids isolated from Aconitum roots exhibit anesthetic effects at peripheral nerves. We performed the present quantitative structure-activity relationship (QSAR) analysis in order to understand the mechanism of action as local anesthetics of 11 Aconitum alkaloids. The alkaloids with the highest anesthetic activity had an aroyl/aroyloxy group at R14 position while the weaker anesthetic alkaloids had the aroyloxy group at R4. The stable compounds exhibited a higher local anesthetic activity than the unstable compounds. In relation to the reactivity indexes of atoms on the aromatic ring, C2' was more reactive while C3' and C5' were less reactive in the compounds with the highest anesthetic activity. Reactivity of N, C1', C4' and C6' was similar between the two groups of alkaloids. The pKa was approximately 7.3 in both groups. The local anesthetic ED50 of alkaloids was significantly inversely related to molecular weight, core-core repulsion energy, steric energy and RI-C2', and directly related to electronic energy, total energy, RI-C5' and to the heat of formation. In conclusion, we identified a set of structural parameters that are related to the local anesthetic activity of Aconitum alkaloids. Our findings are useful to understand the mechanism of action of these alkaloids and to provide a rational for chemical manipulation of the compounds in order to obtain potent derivates with minor toxicity.

A QSAR analysis to explain the analgesic properties of Aconitum alkaloids

Aconitum roots are traditionally prescribed for the management of different types of painful affections in Asiatic countries. A quantitative structure-activity relationship (QSAR) analysis was performed to study the effect of chemical substitutes in the analgesic potency of alkaloids available in Chinese Aconitum roots. Using the CAChe program package for biomolecules, molecular modelling was performed in 12 alkaloids previously tested in a model of acetic acid-induced writhing in rats. The ED50 (micromol/kg) was used as the activity parameter. Structural parameters were compared between alkaloids with an aroyl/aroyloxy group at R14 and alkaloids with the aroyloxy group at R4. Single linear regression analyses were performed in order to find the parameters explaining activity. Alkaloids with an aroyl/aroyloxy group at R14 exhibited the highest potency (significantly less ED50). The stability parameters were different between groups, e.g. total energy was -8.0 +/- 0.4 in the potent analgesic alkaloids and -6.7 +/- 0.3 in the weak analgesic alkaloids (P = 0.001). The reactivity index of C2', C3' and C5' of the aromatic ring was also different between groups, e.g. the reactivity index of C5' was 40.8 +/- 0.6 in potent analgesic alkaloids and 48.1 +/- 0.6 in weaker analgesic alkaloids (P < 0.001). Several structural parameters explained analgesic activity of alkaloids, being the reactivity index of C5' on the aromatic group the most important factor (r = 0.89; P < 0.001).

Analysis of Chinese medicine preparations by capillary electrophoresis–mass spectrometry

In Chinese medicines, herbs are usually prepared before use by patients. Since the preparation procedures convert the original component into one or more products, study of the procedures is usually complex and involves several compounds. On-line coupling of capillary electrophoresis (CE) to mass spectrometry (MS) allows both the efficient separation of CE and the specific and sensitive detection of MS to be achieved. In this study, CE–MS was applied to the determination of alkaloids in Maqianzi (the seed of Strychnos pierrian) and Wutou (aconite root, Radix aconiti praeparata) during the preparation procedure. With optimal CE–MS conditions, alkaloids in both prepared and unprepared Maqianzi were determined successfully in the total ion current (TIC) mode. However, single ion monitoring (SIM) had to be applied for the separation of aconitum alkaloids and their hydrolysis products. Quantification data indicated that MS detection under SIM mode is more sensitive than UV detection. Based on the CE–MS method developed, the hydrolysis of aconitum alkaloids in water and methanol was also studied.

Exploring the ester‐exchange reactions of diester‐diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry

The chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester-exchange reactions for aconitine-type diester-diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of mesaconitine and hypaconitine standards with liquorice root. It was found that diester-diterpenoid aconitines were converted into lipo-alkaloids as well as monoester alkaloids by the decoction of aconite.

Two Survival Cases Of Severe Aconite Poisoning By Percutaneous Cardiopulmonary Support System And Cardiopulmonary Bypass For Fatal Arrhythmia: A Case Report

Objective: to propose adequate treatment of fatal aconite poisoning using percutaneous cardiopulmonary support system and cardiopulmonary bypass. Design: case study. Setting: cardiac care unit in a university hospital. Patient: a 17-yr-old man ingested aconite roots to commit suicide and a 41-yr-old man eaten aconite tubers by accident. Intervention: immediate application of percutaneous cardiopulmonary support system and cardiopulmonary bypass for fatal arrhythmia caused by aconite. Measurements and main results: continuous ecg monitoring was performed. Concentrations of aconites in blood were measured by gas chromatography selected ion monitoring during institution of percutaneous cardiopulmonary support system and cardiopulmonary bypass. The changes of aconite concentration in blood showed that these concentrations are decreased under critical level 24 hours later from ingestion. At the same time fatal arrhythmias were also disappeared. The patients improved fatal arrhythmia and systemic circulation and discharged without neurological deficit. Conclusion: immediate application of percutaneous cardiopulmonary support system and cardiopulmonary bypass enable to survive fatal aconite poisoning patients.

Two Survival Cases Of Severe Aconite Poisoning By Percutaneous Cardiopulmonary Support System And Cardiopulmonary Bypass For Fatal Arrhythmia: A Case Report

Objective: to propose adequate treatment of fatal aconite poisoning using percutaneous cardiopulmonary support system and cardiopulmonary bypass. Design: case study. Setting: cardiac care unit in a university hospital. Patient: a 17-yr-old man ingested aconite roots to commit suicide and a 41-yr-old man eaten aconite tubers by accident. Intervention: immediate application of percutaneous cardiopulmonary support system and cardiopulmonary bypass for fatal arrhythmia caused by aconite. Measurements and main results: continuous ecg monitoring was performed. Concentrations of aconites in blood were measured by gas chromatography selected ion monitoring during institution of percutaneous cardiopulmonary support system and cardiopulmonary bypass. The changes of aconite concentration in blood showed that these concentrations are decreased under critical level 24 hours later from ingestion. At the same time fatal arrhythmias were also disappeared. The patients improved fatal arrhythmia and systemic circulation and discharged without neurological deficit. Conclusion: immediate application of percutaneous cardiopulmonary support system and cardiopulmonary bypass enable to survive fatal aconite poisoning patients.

Norditerpenoid Alkaloids from the Roots of Aconitum leave Royle

AbstractFor Abstract see ChemInform Abstract in Full Text.

Electrospray ionization tandem mass spectrometric study of the aconitines in the roots of aconite.

Fragmentation pathways of aconitine-type alkaloids were investigated by electrospray ionization/ion trap multistage tandem mass spectrometry. Low-energy collision-induced dissociation of protonated aconitines follows a dominant first step, the elimination of the C(8)-substituent as acetic acid or fatty acid in MS(2) spectra. Successive losses of 1-4 CH(3)OH molecules, 1-3 H(2)O, CO, benzoic acid, and CH(3) or C(2)H(5) (N-substituents) are all fragmentation pathways observed in MS(3) and MS(4) spectra. By applying knowledge of these fragmentation pathways to the aconitines in the ethanolic extract of aconite roots, all the known aconitines were detected and also 23 unknown aconitine-type alkaloids, in which the lipo-alkaloids containing residues of 15C, 17C and 19C saturated or unsaturated fatty acids were characterized. These odd-carbon-number fatty acid substituents have not been reported previously.

The effects of higenamine on LPS-induced experimental disseminated intravascular coagulation (DIC) in rats.

The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation (DIC), was investigated using an experimental DIC rat model. The oral administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin degradation product (FDP) level, and the prolongation of prothrombin time (PT) induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of activated partial thrombin time (aPTT) and the decrease of platelet count were suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were also significantly prevented with higenamine. The above results are suggestive that higenamine has therapeutic potential for DIC and/or accompanying multiple organ failure (MOF).

Incidence of herb-induced aconitine poisoning in Hong Kong: impact of publicity measures to promote awareness among the herbalists and the public.

In Hong Kong 'chuanwu' (the main root of Aconitum carmichaeli) and 'caowu' (the root of Aconitum kusnezoffii) are used by herbalists to treat patients with various musculoskeletal disorders. These aconite roots contain aconitine, mesaconitine and hypaconitine, which are neurotoxins and cardiotoxins. During 1989 to 1991, 31 patients were treated in public hospitals because of poisoning by aconite roots and there were two deaths from ventricular arrhythmias. In late 1991, healthcare officials together with cardiologists held a press conference to warn the public, healthcare professionals and herbalists of the potential toxicity of aconite roots. The risk of ventricular arrhythmias and the need for urgent medical attention were highlighted. An information leaflet was also sent to hospital doctors. Since 1992, the topic was covered periodically in the local newspapers, medical journals and continuing medical education programmes. The objective of this study was to assess the impact of these publicity measures on the incidence of herb-induced aconitine poisoning in the New Territories East, based on the number of admissions to the Prince of Wales Hospital. During 1989 to 1993 and 1996 to 1998, all patients admitted to our medical wards because of herb-induced aconitine poisoning were identified by on-going surveillance of medical patients, searching our computerised medical record system and reviewing reports received by the 24-hour Drug and Poisons Information Bureau. The number of hospitalisations due to aconitine poisoning markedly decreased from four to six per year in 1989 to 1991 to one to two per year in 1992 to 1993. The annual incidence of aconitine poisoning showed a marked decrease from 0.49 to 0.69 [overall 0.60, 95% confidence intervals (CI) 0.34 to 0.99] to 0.10 to 0.22 (overall 0.16, 95% CI 0.03 to 0.46) per 100,000 population (p = 0.024). During 1996 to 1998, herb-induced aconitine poisoning remained uncommon, with zero to two hospital admissions per year or an annual incidence of zero to 0.33 (overall 0.17, 95% CI 0.05 to 0.43) per 100,000 population (p = 0.016). It is possible that the herbalists could have used smaller doses of 'chuanwu' and 'caowu' than before. Patients could be more compliant with the instructions on how to prepare the herbal decoction at home. However, our experience suggested that publicity measures to promote awareness, among the herbalists and the public, may reduce the incidence of poisoning due to toxic herbs such as aconite roots.

“Anhydrolycaconitine”, a new diterpene alkaloid fromAconitum septentrionale K

A new alkaloid, anhydrolycaconitine (C36H46N2O9), was isolated from roots ofAconitum septentrionale K. Based on the results of1H and13C NMR and IR spectroscopy and mass spectrometry of the alkaloid and the product of its alkaline hydrolysis and on the data of X-ray diffraction analysis of the hydrolysis product, the structure of 1α, 6β, 14α, 16β-tetramethoxy-7-oxo-18-succinylanthranoyloxy-17-(7→8)abeo-aconane was assigned to anhydrolycaconitine.

Counter Effects of Higenamine and Coryneine, Components of Aconite Root, on Acetylcholine Release from Motor Nerve Terminal in Mice

The counter effects of higenamine and coryneine, components of aconite root, on acetylcholine (ACh) release from motor nerve terminals in the mouse phrenic nerve–diaphragm muscle preparation were studied by a radioisotope method. Both nerve-evoked release and spontaneous release of [3H]-ACh from the preparation preloaded with [3H]-choline were measured. The change in the tetanic tension of muscle was simultaneously recorded in the same preparation. Higenamine (10 μM) augmented both the nerve-evoked and spontaneous ACh releases, and the muscle tension. The effects were inhibited by pretreatment with propranolol (10 μM), a β-adrenoceptor antagonist. Coryneine reduced the nerve-evoked release of ACh, accelerated the decay of tetanic tension (tetanic fade) at 30 μM, and it depressed the peak amplitude of tetanic tension at a higher concentration of 100 μM. These results suggest that of the two components contained in aconite root, higenamine increases ACh release via activation of β-adrenoceptor, and conversely coryneine depresses ACh release by preferentially acting at motor nerve terminal.

Alkaloids ofAconitum tuberosum

The new alkaloid tuberanine has been isolated from the roots ofAconitum tuberosum together with the known alkaloids mesaconitine, aconitine, and flaconitine. The structure of tuberanine has been established on the basis of its spectral characteristics and correlations with mesaconitine. It has been shown that the roots of this plant can serve as a source of raw material for obtaining the alkaloid mesaconitine.

The effects of Aconitum alkaloids on the central nervous system

Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the central nervous system. The pharmacological effects of preparations of Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na + channels by binding to neurotoxin binding site 2 of the α-subunit of the channel protein. In this article the pharmacology of several structurally related Aconitum alkaloids is highlighted and their therapeutic vs toxic potential is discussed. Neurochemical and neurophysiological studies will be reviewed with emphasis on the effects of the alkaloids in regions of the brain that have been implicated in pain transmission and generation of epileptic activity. Considering the chemical structure of the Aconitum alkaloids as well as their mechanism of action, a subdivision in three groups becomes obvious: the first group comprises such alkaloids which possess high toxicity due to two ester boundings at the diterpene skeleton. The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake. Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties. The second group comprises less toxic monoesters which have been shown to possess strong antinociceptive, antiarrhythmic and antiepileptiform properties due to a blockade of the voltage-dependent sodium channel. Electrophysiological studies have revealed a use-dependent inhibition of neuronal activity by these alkaloids. They seem to be competitive antagonists of the group I-alkaloids. The third group of Aconitum alkaloids are lacking an ester side chain in the molecule. Toxicity is markedly reduced when compared with the two other groups. They fail to affect neuronal activity, but are reported to have antiarrhythmic actions suggesting that they may have different affinities to various subtypes of the α-subunit of the Na + channel in brain and heart.

A study ofaconitum alkaloids from aconite roots inAconitum carmichaeli Debx using matrix-assisted laser desorption/ionization mass spectrometry

In the present paper a study of C19-diterpene type of aconitum alkaloids, extracted from aconite roots in Aconitum carmichaeli Debx has been made using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOFMS). The results demonstrated that the aconitum alkaloids from aconite roots can be determined simultaneously by this method, which was found to be superior to other analytical methods with regard to speed and sensitivity. Fourteen known aconitum alkaloids, including aconitines, benzoylaconitines and lipoaconitines, were assigned in the methanol extract and three compounds not reported before have been targeted separation. The evaluation of the efficiency of different extractions has been studied. These results suggested that the differences of the polarity and basicity of aconitine, and benzoylaconitines and lipoaconitines result from the C-8 constituent groups that are easily lost under MALDI. © 1998 John Wiley & Sons, Ltd.

A Case of Aconite Intoxication and Recurrent Ventricular Arrhythmia without Apparent Myocardial Damage after 20,680 Joules DC Shock

The aconite root has been used in oriental medicine to improve metabolism of debilitated patient and to cure acute dysuria, cardiac weakness, gout, neuralgias and rheumatism. The crude drug “ bu-shi” or “ cho-oh” , which is obtained from the Aconitum roots, contains the potent poisons aconitine, mesaconitine, jesaconitine, and hypaconitine, which are C19 diterpenoid ester alkaloids. These alkaloids have been known to induce fatal cardiac arrhythmias, such as ventricular tachycardia, and ventricular fibrillation. In ventricular tachycardia or fibrillation, cardioversion/defibrillation are the most effective treatment of choice to terminate reentrant arrhythmias. Through animal experiments, it has been known that repeated delivery of high energy DC shocks cause some myocardial damage, and the severity of myocardial damage is proportional to the delivered energy. The paddle size, defibrillation interval and total delivered energy have also been known to be associated with the severity of injury. But in humans, the amount of energy that causes myocardial damage or dysfunction has not been studied. Therefore it is necessary that a quantitative study on this issue in conjunction with the amount of each delivered energy and the interval between electrical shocks should be done. We experienced a 36 year old man who complained nausea, vomiting, dizziness and generalized weakness and showed hemodynamic compromise with recurrent ventricular tachyarrhythmias such as bidirectional ventricular tachycardia, Torsades de pointes and ventricular fibrillation. This patient was resuscitated with repeated cardioversion/defibrillation of 20,680 Joules for 8 hours and 30 minutes, but did not show significant myocardial damage.