aconitine and hypaconitine

aconitine has been researched along with hypaconitine* in 75 studies

Reviews

1 review(s) available for aconitine and hypaconitine

ArticleYear
Aconitine poisoning due to Chinese herbal medicines: a review.
    Veterinary and human toxicology, 1994, Volume: 36, Issue:5

    Both "chuanwu", the main root of Aconitum carmichaeli, and "caowu", the root of A kusnezoffii, are believed to possess anti-inflammatory, analgesic and cardiotonic effects and have been used in Chinese materia medica mainly for the treatment of musculoskeletal disorders. They contain the highly toxic C19 diterpenoid alkaloids of aconitine, mesaconitine and hypaconitine. After ingestion, patients may present with signs and symptoms that are typical of aconitine poisoning. Death may occur from ventricular arrhythmias, which are most likely to occur within the first 24 h. Management of aconitine poisoning is essentially supportive. There are no adequate studies in humans to indicate the most effective treatment of the ventricular arrhythmias. All clinicians should be alerted to the potential toxicity of "chuanwu" and "caowu".

    Topics: Aconitine; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Drugs, Chinese Herbal; Female; Heart Ventricles; Hong Kong; Humans; Male; Middle Aged; Neuromuscular Blocking Agents; Poisoning; Retrospective Studies; Sodium Channels

1994

Other Studies

74 other study(ies) available for aconitine and hypaconitine

ArticleYear
Investigation into the protective effects of hypaconitine and glycyrrhetinic acid against chronic heart failure of the rats.
    BMC complementary medicine and therapies, 2022, Jun-16, Volume: 22, Issue:1

    The present study aimed to determine the protective effects of hypaconitine (HA) and glycyrrhetinic acid (GA) against chronic heart failure (CHF) in the rats and to explore the underlying molecular mechanisms.. The CHF rat model was established by transverse-aortic constriction (TAC) operation. Transthoracic echocardiography and hematoxylin eosin (HE) staining were used to evaluate the pathophysiological and histopathological changes of CHF model. The total cholesterol (TCHO) and triglyceride (TG) levels were determined by ELISA assay. The protein expression of fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) in the rat ventricular tissues was determined by immunohistochemistry. The serum metabolites were determined by LC-MS/MS assay.. After applied the HA + GA, the cardiac tissue and structure were obviously improved, and the HA + GA treatment also significantly reduced the plasma levels of TCHO and TG in the CHF rats. The expression of FGF2 and VEGFA protein was up-regulated and the expression of eNOS protein was down-regulated in the ventricular tissues of CHF rats, which was significantly restored after HA + GA treatment. HA + GA treatment down-regulated serum isonicotinic acid, phosphatidylcholine, cardiolipin, estrogen glucuronide, and glycocholic acid, up-regulated serum sphingosine and deoxycholic acid in the CHF rats.. In conclusion, HA + GA showed protective effects on CHF in the rats, and the HA + GA may exert protective effects by reducing lipid levels, up-regulating the expression of FGF2 and VEGFA proteins, attenuating eNOS protein expression, and modulating metabolic pathways. However, the molecular mechanisms underlying HA + GA-mediated effects still require further examination.

    Topics: Aconitine; Animals; Chromatography, Liquid; Fibroblast Growth Factor 2; Glycyrrhetinic Acid; Heart Failure; Rats; Tandem Mass Spectrometry; Vascular Endothelial Growth Factor A

2022
[Comparative study on intestinal absorption kinetics of main active components in Sini Decoction and its separated recipes].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2022, Volume: 47, Issue:18

    This paper aims to study the difference in the intestinal absorption kinetics of main active components of Sini decoction and its separated recipes and explain the scientificity and rationality of the compatibility of Sini Decoction. A in situ intestinal perfusion rat model was established to evaluate the differences in the absorption of benzoylmesaconine, benzoylaconine, benzoylhypacoitine, mesaconitine, hypaconitine, glycyrrhizic acid, liquiritin and 6-gingerol from Sini Decoction and its separated recipes in the duodenum, jejunum and ileum by high performance liquid chromatography(HPLC). The results indicated that the Sini Decoction group was superior to the Aconiti Lateralis Radix Praeparata group in terms of absorption degree and rate for aconitum alkaloids. The absorption of benzoylmesaconine and hypaconitine in the duodenum, jejunum and ileum was faster and stronger in the Sini Decoction group(P<0.05). The absorption degree of glycyrrhizic acid in the duodenum was significantly higher in the Sini Decoction group than in the Glycyrrhizae Radix et Rhizoma group and the Glycyrrhizae Radix et Rhizoma-Zingiberis Rhizoma group(P<0.05). The absorption rate and degree of 6-gingerol in the ileum in the Sini Decoction group were significantly higher than those in the Zingiberis Rhizoma group(P<0.05). In short, Zingiberis Rhizoma and Glycyrrhizae Radix et Rhizoma can promote the absorption of aconitum alkaloids in different intestinal segments, which reflects the scientific composition of Sini Decoction.

    Topics: Aconitine; Aconitum; Alkaloids; Animals; Catechols; Drugs, Chinese Herbal; Fatty Alcohols; Glycyrrhizic Acid; Intestinal Absorption; Kinetics; Rats

2022
    Journal of natural products, 2021, 03-26, Volume: 84, Issue:3

    The lateral roots of

    Topics: Aconitine; Aconitum; Alkaloids; China; Chromatography, Liquid; Diterpenes; Drug Contamination; Drugs, Chinese Herbal; Mass Spectrometry; Medicine, Chinese Traditional; Molecular Structure; Plant Roots

2021
Pharmacokinetics-based chronoefficacy of Fuzi against chronic kidney disease.
    The Journal of pharmacy and pharmacology, 2021, Mar-08, Volume: 73, Issue:4

    Identifying drugs with time-varying efficacy or toxicity, and understanding the underlying mechanisms would help to improve treatment efficacy and reduce adverse effects. In this study, we uncovered that the therapeutic effect of Fuzi (the lateral root of Aconitum carmichaelii Debeaux) depended on the dosing time in mice with adenine-induced chronic kidney disease (CKD).. The Fuzi efficacy was determined by biomarker measurements [i.e. plasma creatinine (CRE), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG)], as well as inflammation, fibrosis and histological analyses. Circadian regulation of Fuzi pharmacokinetics and efficacy was evaluated using brain and muscle Arnt-like protein-1 (Bmal1)-deficient (Bmal1-/-) mice.. The Fuzi efficacy was higher when the drug was dosed at ZT10 and was lower when the drug was dosed at other times (ZT2, ZT6, ZT14, ZT18 and ZT22) according to measurements of plasma CRE, BUN and urinary NAG. Consistently, ZT10 (5 PM) dosing showed a stronger protective effect on the kidney (i.e. less extensive tubular injury) as compared to ZT22 (5 AM) dosing. This was supported by lower levels of inflammatory and fibrotic factors (IL-1β, IL-6, Tnf-α, Ccl2, Tgfb1 and Col1a1) at ZT10 than at ZT22. Pharmacokinetic analyses showed that the area under the curve (AUC) values (reflective of systemic exposure) and renal distribution of aconitine, hypaconitine and mesaconitine (three putative active constituents) for Fuzi dosing at ZT10 were significantly higher than those for herb dosing at ZT22, suggesting a role of circadian pharmacokinetics in Fuzi chronoefficacy. Drug efficacy studies confirmed that aconitine, hypaconitine and mesaconitine possessed a kidney-protecting effect. In addition, genetic knockout of Bmal1 in mice abolished the time-dependency of Fuzi pharmacokinetics and efficacy. This reinforced the existence of chronoefficacy for Fuzi and supported the role of circadian pharmacokinetics in Fuzi chronoefficacy.. The efficacy of Fuzi against CKD depends on the dosing time in mice, which is associated with circadian pharmacokinetics of the three main active constituents (i.e. aconitine, hypaconitine and mesaconitine). These findings highlight the relevance of dosing time in the therapeutic outcomes of herbal medicines.

    Topics: Aconitine; Alkaloids; Animals; Anti-Inflammatory Agents; ARNTL Transcription Factors; Chronopharmacokinetics; Diterpenes; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Kidney Function Tests; Mice; Mice, Knockout; Plant Roots; Protective Agents; Renal Insufficiency, Chronic; Treatment Outcome

2021
Circadian clock regulates metabolism and toxicity of Fuzi(lateral root of Aconitum carmichaeli Debx) in mice.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2020, Volume: 67

    Therapeutic applications of Fuzi (lateral root of Aconitum carmichaeli Debx) are seriously concerned with its toxic effects. Strategies and approaches to reducing toxicity are of great interest.. We aimed to characterize the diurnal rhythm of Fuzi toxicity, and to determine the role of metabolism and pharmacokinetics in generating toxicity rhythmicity.. Toxicity was determined based on assessment of heart injury and animal survival after dosing mice with Fuzi decoction at different circadian time points. Circadian clock control of pharmacokinetics and toxicity was investigated using Bmal1-deficient (Bmal1. Fuzi exhibited a diurnal rhythmicity in cardiotoxicity (reflected by plasma CK-MB and LDH levels). The highest level of toxicity was observed at ZT10 (5 PM), while the lowest level of toxicity occurred at ZT22 (5 AM). Also, a higher mortality rate was observed at ZT10 and lower mortality rates at other times of the day. ZT10 dosing of Fuzi generated higher systemic exposures of three toxic alkaloid ingredients aconitine (AC), hypaconitine (HA) and mesaconitine (MA) compared to ZT22. This was accompanied by reduced the formation of the metabolites (N-deethyl-AC, didemethyl-HA and 2‑hydroxyl‑MA) at ZT10. Bmal1 ablation resulted in an increased level of Fuzi toxicity at ZT22, while having no influences when drug was dosed at ZT10. As a consequence, circadian time-dependent toxicity of Fuzi was lost in Bmal1-deficient mice. In addition, Bmal1 ablation increased the plasma concentrations of AC, HA and MA in mice after oral gavage of Fuzi, and reduced formation of their metabolites (N-deethyl-AC, didemethyl-HA and 2‑hydroxyl‑MA). Moreover, Fuzi metabolism in wild-type liver microsomes was more extensive at ZT22 than at ZT10. Bmal1 ablation abrogated circadian time-dependency of hepatic Fuzi metabolism.. Fuzi chronotoxicity in mice was attributed to time-varying hepatic metabolism and systemic exposure regulated by circadian clock. The findings may have implications in reducing Fuzi toxicity with a chronotherapeutic approach.

    Topics: Aconitine; Aconitum; Animals; ARNTL Transcription Factors; Chromatography, High Pressure Liquid; Circadian Clocks; Diterpenes; Drugs, Chinese Herbal; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microsomes, Liver; Plant Extracts; Toxicity Tests

2020
A proton-coupled organic cation antiporter is involved in the blood-brain barrier transport of Aconitum alkaloids.
    Journal of ethnopharmacology, 2020, Apr-24, Volume: 252

    The herbs of Aconitum are the essential Traditional Chinese medicine and have played an indispensable role in many Asian countries for thousands of years to treat critical illnesses, and chronic, stubborn diseases. However, Aconitum may induce severe neurotoxicity and even death. So far the mechanism of Aconitum penetrating the blood-brain barrier (BBB) is still unclear.. To determine whether influx transporters contribute to the brain uptake of the highly toxic alkaloids in Aconitum including aconitine (AC), mesaconitine (MA) and hypaconitine (HA).. A novel proton-coupled organic cation antiporter plays a predominant role in the blood to brain influx of AC, MA and HA at the BBB, and thus affect the safety of Aconitum species.

    Topics: Aconitine; Aconitum; Animals; Antiporters; Blood-Brain Barrier; Cell Line; Humans; Male; Mice, Inbred ICR; Organic Cation Transport Proteins; Protons; RNA, Small Interfering

2020
Mdr1a, Bcrp and Mrp2 regulate the efficacy and toxicity of mesaconitine and hypaconitine by altering their tissue accumulation and in vivo residence.
    Toxicology and applied pharmacology, 2020, 12-15, Volume: 409

    Topics: Aconitine; Alkaloids; Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Biological Transport; Brain; Gene Knockout Techniques; Male; Mice; Mice, Knockout; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins

2020
The mechanism underlying hypaconitine-mediated alleviation of pancreatitis-associated lung injury through up-regulating aquaporin-1/TNF-α.
    The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2020, Volume: 31, Issue:11

    Acute pancreatitis-associated lung injury (APALI) is one of the most common and most dangerous form of extra-pancreatic organ damage in severe acute pancreatitis (SAP). The treatment options for SAP were limited thus far; as a result, approximately 60%-80% of patients with SAP would die within a week. Hypaconitine (HC), one of the most important active ingredients in a Mongolian traditional medicine Radix Aconiti Kusnezoffii has an excellent anti-inflammatory effect.. To ascertain whether HC has a protective effect against APALI, we investigated the therapeutic effects and the underlying mechanisms in vivo and in vitro and attempted to elucidate the mechanism in detail. In this study, APALI rats and human pulmonary microvascular endothelial cells were treated with therapeutic doses of HC after establishing a model with sodium taurocholate and lipopolysaccharide, respectively.. Serum amylase and lipase activity, lung wet/dry weight ratio, lung myeloperoxidase activity, and pancreatic and lung histopathological changes showed that HC alleviated APALI in a dose-dependent way, which can be abolished by an aquaporin-1 (AQP-1) knockdown. The results of the reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemical staining confirmed the expression of AQP-1, a kind of transmembrane protein that mainly distributed in the membranes of pulmonary cells and contributed to maintain water balance in the body by interacting with tumor necrosis factor-alpha (TNF-α), is negatively associated with APALI. On the contrary, HC treatment up-regulated AQP-1 expression and down-regulated the TNF-α expression as a consequence in APALI.. These results suggest that HC has a good anti-inflammatory therapeutic effect on APALI with a possible underlying mechanism that affects the AQP-1/TNF-α pathway.

    Topics: Aconitine; Acute Disease; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Aquaporin 1; Dose-Response Relationship, Drug; Endothelial Cells; Humans; Lung; Male; Microvessels; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Respiratory Mucosa; Signal Transduction; Tumor Necrosis Factor-alpha; Up-Regulation

2020
Simultaneous high-performance liquid chromatography with tandem mass spectrometry quantification of six bioactive components in rat plasma after oral administration of Yougui pill.
    Journal of separation science, 2019, Volume: 42, Issue:10

    Yougui pills are a classic Chinese medicine that shows significant effects on nerve regeneration and neuroprotection in modern pharmacological studies. With a complex formula, Yougui pills have faced significant challenges in the fields of bioanalysis and pharmacokinetics in animals and human studies. In the present study, a specific and accurate high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the quantitative determination of the six bioactive components in rat plasma after oral administration of Yougui pills. Chromatographic separation was performed on a C18 column with a gradient elution system. Samples were analysed using positive ion mode with multiple reaction monitoring mode. The assay showed good linearity for all six bioactive components in the dynamic range of 0.50 to 50 ng/mL with acceptable intra- and inter-batch accuracy and precision. The lower limits of quantification were 0.50 ng/mL for all six bioactive components. The method was successfully applied to rat pharmacokinetics after oral administration of Yougui pills. All six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside, while some other target compounds were not detected, such as rhmannioside A, loganin, and cornuside I. After oral administration of Yougui pills at a dose of 2500 mg/kg, all six bioactive components were rapidly absorbed, resulting in t

    Topics: Aconitine; Administration, Oral; Alkaloids; Animals; Calibration; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Ions; Iridoid Glucosides; Male; Plant Extracts; Quality Control; Rats; Rats, Inbred Lew; Reproducibility of Results; Tandem Mass Spectrometry

2019
Rapid identification of herbal toxins using electrospray laser desorption ionization mass spectrometry for emergency care.
    Journal of food and drug analysis, 2019, Volume: 27, Issue:2

    The unintentional ingestion of toxic compounds in herbs is not uncommon in many parts of the world. To provide timely and life-saving care in the emergency department, it is essential to develop a point-of-care analytical method that can rapidly identify these toxins in herbs. Since electrospray laser desorption ionization mass spectrometry (ELDI/MS) has been successfully used to characterize non-volatile chemical compounds without sample preparation, it was used to identify toxic herbal compounds in this study. The herbal toxins were collected either by sweeping a metallic probe across the surface of a freshly cut herb section or by directly sampling extracts of ground herbal powder. The analytes on the probe were then desorbed, ionized and detected using ELDI/MS, wherein analysis of the herbal toxins was completed within 30 s. This approach allows for the rapid morphological recognition of herbs and early point-of-care identification of herbal toxins for emergency management and is promising in providing important toxicological information to ensure appropriate medical treatment.

    Topics: Aconitine; Emergency Medical Services; Flavanones; Humans; Plants, Toxic; Pyridoxine; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Toxins, Biological

2019
Circadian Cyp3a11 metabolism contributes to chronotoxicity of hypaconitine in mice.
    Chemico-biological interactions, 2019, Aug-01, Volume: 308

    Hypaconitine is an active and highly toxic constituent derived from Aconitum species. Here we aimed to determine the chronotoxicity of hypaconitine in mice, and to investigate a potential role of metabolism in hypaconitine chronotoxicity. Cardiac toxicity was assessed by measuring CK (creatine kinase) and LDH (lactate dehydrogenase) levels after hypaconitine administration to wild-type and Bmal1

    Topics: Aconitine; Animals; ARNTL Transcription Factors; Circadian Clocks; Creatine Kinase; Cytochrome P-450 CYP3A; Half-Life; HEK293 Cells; Humans; Liver; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Microsomes, Liver; RNA, Messenger

2019
Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion, migration, and invasion of lung cancer A549 cells.
    Chinese journal of natural medicines, 2017, Volume: 15, Issue:6

    Epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis and provides novel strategies for cancer therapy. Hypaconitine (HpA), a diester-diterpenoid alkaloid isolated from the root of the Aconitum species, exhibits anti-inflammatory, analgesic, and especially, cardiotoxic activities. Here, we reported the anti-metastatic potentials of HpA in transforming growth factor-β1 (TGF-β1)-induced EMT in lung cancer A549 cells. The cytotoxic effect of HpA was determined by MTT assay. A549 cells were treated with TGF-β1 with or without HpA co-treatment, and the morphological alterations were observed with a microscopy. The expression of E-cadherin, N-cadherin, and NF-κB was determined by both Western blotting and immunofluorescence analyses. The adhesion, migration, and invasion were detected with Matrigel, wound-healing, and transwell assays, respectively. The expression of Snail was determined by Western blotting. The expression of NF-κB p65, IκBα, and p-IκBα in nuclear and cytosolic extracts was assessed by Western blotting. The results showed that low concentration of HpA (<16 μmol·L

    Topics: A549 Cells; Aconitine; Active Transport, Cell Nucleus; Antineoplastic Agents, Phytogenic; Cadherins; Cell Adhesion; Cell Movement; Dose-Response Relationship, Drug; Epithelial-Mesenchymal Transition; Humans; Neoplasm Invasiveness; NF-kappa B; Transforming Growth Factor beta1

2017
Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury.
    Journal of Zhejiang University. Science. B, 2017, Volume: 18, Issue:7

    This study investigated the protective effect of the compatibility of hypaconitine (HA) and glycyrrhetinic acid (GA) on H9c2 cells under oxygen and glucose deprivation (OGD)-induced injury, and the possible mechanisms. We found that HA+GA significantly improved pathology and morphology of the nucleus and ultrastructure of H9c2 cells under OGD as determined by Hoechst 33342 staining and transmission electron microscopy (TEM) tests. It also reduced the releases of lactate dehydrogenase (LDH), creatine kinase-myocardial band isoenzyme (CK-MB), and aspartate transaminase (AST) from the cultured supernatant of H9c2 cells, which were tested by enzyme-linked immune sorbent assay (ELISA) kits. In addition, it lessened the apoptotic rate as determined by a fluorescein isothiocyanate-annexin V/propidium iodide (FITC-AV/PI) double staining assay. It was also found that HA+GA might regulate the protein expression associated with the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Overall, the study demonstrated that HA+GA protected H9c2 cells against OGD-induced injury, and the signaling mechanism might be related to the PI3K/Akt signaling pathway.

    Topics: Aconitine; Aconitum; Animals; Anti-Inflammatory Agents; Apoptosis; Cell Survival; Creatine Kinase, MB Form; Enzyme-Linked Immunosorbent Assay; Glucose; Glycyrrhetinic Acid; Heart Diseases; L-Lactate Dehydrogenase; Microscopy, Electron, Transmission; Necrosis; Oxygen; Phosphatidylinositol 3-Kinases; Rats; Signal Transduction

2017
Histone deacetylase-high mobility group box-1 pathway targeted by hypaconitine suppresses the apoptosis of endothelial cells.
    Experimental biology and medicine (Maywood, N.J.), 2017, Volume: 242, Issue:5

    Hypaconitine is an active component of Aconitum carmichaelii Debx, a Chinese medicinal herb for the treatment of cardiovascular diseases, but the mechanism underlying its effect remains elusive. In this study, we found that hypaconitine, rather than aconitum alkaloids in A. carmichaelii (e.g. aconitine, mesaconitine and benzoylaconitine), prevented endothelial cells from damage due to oxidized low-density lipoprotein (oxLDL) challenge. Cleaved caspase 3 expression in endothelial cells was up-regulated by oxLDL and markedly attenuated by hypaconitine, suggesting that hypaconitine inhibited the oxLDL-induced cell apoptosis. Microarray analysis revealed that histone deacetylase 3 (HDAC3) was significantly increased by hypaconitine. The cytoplasmic relocation and extracellular release of high-mobility group box 1 (HMGB1, an HDAC3 downstream effector) in endothelial cells were significantly increased by oxLDL and markedly decreased by hypaconitine. The effect of hypaconitine on the oxLDL-induced apoptosis and HMGB1 release in endothelial cells was significantly reduced by the suppression of HDAC3 by siRNA or a specific inhibitor. Thus, this study proves that the histone deacetylase-HMGB1 pathway targeted by hypaconitine suppresses the apoptosis of endothelial cells. Our findings are of therapeutic significance and provide the potential of hypaconitine exploitation. Impact statement First, our study shows the antiapoptosis effect of Aconitum carmichaelii and its active component hypaconitine on endothelial cells. It may provide new strategies for the treatment of diseases involving endothelium damage. Second, this finding indicates the function of hypaconitine in regulating HDAC3-HMGB1 pathway, which suggests a new anti-inflammatory therapy. Third, due to its poisonousness, A. carmichaelii is always used with caution in clinics. Thus, the identification of hypaconitine as an active component of A. carmichaelii could contribute to the development of toxicity-decreasing procedure for A. carmichaelii.

    Topics: Aconitine; Aconitum; Apoptosis; Blotting, Western; Cell Line; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Histone Deacetylases; HMGB1 Protein; Humans; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; Signal Transduction

2017
Comparative pharmacokinetics of hypaconitine after oral administration of pure hypaconitine, Aconitum carmichaelii extract and Sini Decoction to rats.
    Molecules (Basel, Switzerland), 2015, Jan-16, Volume: 20, Issue:1

    Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii (AC), which is considered to be effective on cardiovascular disease, although it also has high toxicity. Sini Decoction (SND), composed of Aconitum carmichaelii, Glycyrrhiza uralensis and Zingiber officinale, is a traditional Chinese multi-herbal formula for recuperating the depleted yang. The aim of this study was to compare the pharmacokinetics of HC in rat plasma after oral administration of HC, AC extract and SND, and investigate the effect of other two herbal ingredients on absorption, metabolism and elimination of HC. A sensitive and specific LC-MS/MS method was developed to determine HC in rat plasma. Eighteen male Sprague-Dawley rats were randomly assigned to three groups: HC, AC and SND group. Plasma concentrations of HC were determined at designated points after oral administration, and main pharmacokinetic parameters were estimated. It was found that there was obvious difference (p < 0.05) on the pharmacokinetic parameters among three groups. Compared with AC group, Tmax, Cmax, k, AUC(0-24) and AUC(0-∞) decreased in SND group, while t1/2 and MRT had been lengthened, which indicated that the ingredients in other two herbs could influence the pharmacokinetic behavior of HC.

    Topics: Aconitine; Aconitum; Administration, Oral; Animals; Drugs, Chinese Herbal; Male; Plant Extracts; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Time Factors

2015
Pharmacokinetics of aconitine-type alkaloids after oral administration of Fuzi (Aconiti Lateralis Radix Praeparata) in rats with chronic heart failure by microdialysis and ultra-high performance liquid chromatography-tandem mass spectrometry.
    Journal of ethnopharmacology, 2015, May-13, Volume: 165

    Fuzi [the lateral root of Aconitum carmichaeli Debx (Ranunculaceae)] is a well-known traditional medicinal herb used to treat chronic heart failure (CHF). Aconitine-type alkaloids are major alkaloids that are responsible for the pharmacological activity and toxicity of this herb.To investigate therapeutic effects and pharmacokinetic profiles of aconitine-type alkaloids in CHF rats.. The plasma pharmacokinetic profiles of aconitine, mesaconitine, and hypaconitine were investigated after once treatment of Fuzi extract (containing aconitine 0.086 mg/g, mesaconitine 0.84 mg/g, and hypaconitine 1.97 mg/g) using a rapid and sensitive combinative method of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and microdialysis (MD). The cardiac function and antioxidant enzyme activities were also evaluated.. Recoveries of MD sampling ranged from 35.06% to 45.74% with RSD below 6.05%. Fuzi extract improved the myocardial function and antioxidant enzymatic activities of rats with CHF. Aconitine, mesaconitine, and hypaconitine exhibited slower absorption into the bloodstream, and yielded 11-fold less values of area under concentration-time curve (AUC) in the CHF rats than those in normal rats. The plasma AUC showed that the maximum blood concentration (Cmax) was 5.561 ng/mL for aconitine, 17.30 ng/mL for mesaconitine, and 17.78 ng/mL for hypaconitine in normal rats, while these were 0.6059 ng/mL, 2.430, and 0.7461 ng/mL in CHF rats, respectively.. Aconitine-type alkaloids associated with Fuzi׳s efficacy have lower intake and slower elimination in the CHF rats, indicating a non-interdependent relationship between its efficacy and toxicity. It may contribute to the depth understanding of the toxicological and pharmacological profiles of Fuzi and further benefit the herbal drug development with safety and efficacy for CHF treatment.

    Topics: Aconitine; Aconitum; Administration, Oral; Animals; Chromatography, High Pressure Liquid; Diterpenes; Drugs, Chinese Herbal; Heart Failure; Male; Microdialysis; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

2015
Hypaconitine-induced QT prolongation mediated through inhibition of KCNH2 (hERG) potassium channels in conscious dogs.
    Journal of ethnopharmacology, 2015, May-26, Volume: 166

    Hypaconitine is one of the main aconitum alkaloids in traditional Chinese medicines prepared with herbs from the genus Acotinum. These herbs are widely used for the treatment of cardiac insufficiency and arrhythmias. However, Acotinum alkaloids are known for their toxicity as well as their pharmacological activity, especially cardiotoxicity including QT prolongation, and the mechanism of this toxicity is not clear.. In this study, hypaconitine was administered orally to conscious Beagle dogs, and electrocardiograms were recorded by telemetry. Pharmacokinetic studies (6h) were conducted to evaluate the relationship between QT prolongation and exposure level. HEK293 cells stably transfected with KCNH2 (hERG) cDNA were used to examine the effects of hypaconitine on the KCNH2 channel by using the manual patch clamp technique.. In the conscious dogs, all doses of hypaconitine induced QTcV (QT interval corrected according to the Van de Water formula) prolongation by more than 23% (67ms) of control in a dose-dependent manner. The maximum QTcV prolongation was observed at 2h after dosing. Maximum prolongation percentages were plotted against plasma concentrations of hypaconitine and showed a strong correlation (R(2)=0.789). In the in vitro study in HEK293 cells, hypaconitine inhibited the KCNH2 currents in a concentration-dependent manner with an IC50 of 8.1nM.. These data suggest that hypaconitine inhibits KCNH2 potassium channels and this effect might be the molecular mechanism underlying QT prolongation in conscious dogs.

    Topics: Aconitine; Animals; Cell Line; DNA, Complementary; Dogs; Electrocardiography; Ether-A-Go-Go Potassium Channels; Female; HEK293 Cells; Humans; Male; Medicine, Chinese Traditional; Potassium Channel Blockers; Potassium Channels

2015
Analgesic activity of diterpene alkaloids from Aconitum baikalensis.
    Bulletin of experimental biology and medicine, 2014, Volume: 157, Issue:4

    We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation.

    Topics: Acetic Acid; Aconitine; Aconitum; Alkaloids; Analgesics; Animals; Animals, Outbred Strains; Arthritis, Experimental; Dipyrone; Freund's Adjuvant; Injections, Intraperitoneal; Mice; Pain; Plant Extracts; Rats; Seizures; Vocalization, Animal

2014
Distribution of toxic alkaloids in tissues from three herbal medicine Aconitum species using laser micro-dissection, UHPLC-QTOF MS and LC-MS/MS techniques.
    Phytochemistry, 2014, Volume: 107

    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.

    Topics: Aconitine; Aconitum; Alkaloids; Drugs, Chinese Herbal; Molecular Structure; Plant Roots

2014
Study on intestinal absorption and pharmacokinetic characterization of diester diterpenoid alkaloids in precipitation derived from fuzi-gancao herb-pair decoction for its potential interaction mechanism investigation.
    Journal of ethnopharmacology, 2013, May-02, Volume: 147, Issue:1

    Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating.. In present study, we focus on Fuzi-Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi-Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated.. Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed.. In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1(st) order absorption and lag time.. Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi-Gancao herb-pair.

    Topics: Aconitine; Aconitum; Administration, Oral; Alkaloids; Animals; Biological Transport; Chemical Precipitation; Diterpenes; Drugs, Chinese Herbal; Esters; Intestinal Absorption; Intestine, Small; Male; Medicine, Chinese Traditional; Models, Biological; Perfusion; Phytotherapy; Plants, Medicinal; Rats; Rats, Sprague-Dawley

2013
[Rationality of the processing methods of aconiti lateralis radix (Fuzi) based on chemical analysis].
    Yao xue xue bao = Acta pharmaceutica Sinica, 2013, Volume: 48, Issue:2

    In this study, we explored the rationality of processing methods and mechanism of Aconiti Lateralis Radix (Fuzi) through comparing the chemical contents of diester alkaloids (DAs) and monoester alkaloids (MAs) in the raw material of Fuzi and its processed products. The results showed that the toxicity potency of MAs is at least lower than 1/64 to 1/180 of the toxicity potency of DAs. The contents of DAs in processed Fuzi decreased to 1/76.5 to 1/38.3 of the value of raw Fuzi. The contents of MAs in processed Fuzi significantly increased by 4.6 to 5.2 fold or basically the same as that of the raw Fuzi. The values of MAs/DAs of processed Fuzi were enhanced by 30 to 390 fold of the raw Fuzi. It was found that the contents of DAs were insignificantly different between "Wu dan fu pian" (steaming or stir-frying without Danba) and "Dan fu pian" (steaming or stir-frying with Danba). The result suggested that the abilities of "eliminating toxicity" of different processing methods were equivalent at all. In contrast, the contents of MAs contained in "Wu dan fu pian" were of 5.3 to 8.7 fold higher than the values in "Dan fu pian". This result suggested the processing method by steaming or stir-frying without Danba might have better effect for "conserving property" than the method processed with Danba stipulated by China Pharmacopoeia. We believe that the new processing method without Danba can be recommended in further application due to it offers a simple procedure and it will not introduce inorganic impurities in the products.

    Topics: Aconitine; Aconitum; Animals; Chromatography, High Pressure Liquid; Cluster Analysis; Drugs, Chinese Herbal; Male; Rats; Rats, Sprague-Dawley; Technology, Pharmaceutical

2013
The effects of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids in herb couple of Radix Aconiti Lateralis-Rhizoma Zingiberis.
    Journal of ethnopharmacology, 2013, Jul-09, Volume: 148, Issue:2

    Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy.. In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi-Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi-Ganjiang aqueous extract was carried out.. A sensitive, specific and rapid LC-MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi-Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0).. Comparing with Fuzi group, both T1/2 and AUC0-t of AC and HA decreased (P<0.05), while T1/2, AUC0-t and Cmax of BAC, BHA increased (P<0.05) in Fuzi-Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA.. The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi-Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi-Ganjiang to decrease toxicity and increase efficacy.

    Topics: Aconitine; Aconitum; Alkaloids; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Diterpenes; Drugs, Chinese Herbal; Male; Mass Spectrometry; Medicine, Chinese Traditional; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley; Rhizome; Tandem Mass Spectrometry; Zingiber officinale

2013
[Determination of aconitine, hypaconitine and mesaconitine in Shenfu injection].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2013, Volume: 38, Issue:10

    To establish a method for the content determination of indexes for measuring aconitic compounds contained in Shenfu injection, in order to provide basis for the evaluation of the curative effect of monkshood in Shenfu injection. The sample were purified and enriched with HF-LPME. ACQUITY UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was adopted and eluted with a gradient program, with acetonitrile-10 mmol x L(-1) NH4HCO3 (pH 10) as the mobile phases. The flow rate was 0.45 mL x min(-1). The content was determined with ESI and MRM. The results showed that aconitine, hypaconitine and mesaconitine showed a good linear relationship, with r > 0.999, within the range of 0.1-100 ng x L(-1). The recoveries were detected to be 100.1%, 97.4%, 97.5%, with RSD being 1.2%, 1.1%, 1.5%, respectively. This method was used to prove the safety of Shenfu injection, and provide scientific basis for correct evaluation of curative effect of monkshood, as well as a reliable, simple and practical means for quality control of monkshood-containing Chinese materia medica preparations.

    Topics: Aconitine; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Mass Spectrometry; Quality Control

2013
[Case of fatal aconite poisoning, and its background].
    Shokuhin eiseigaku zasshi. Journal of the Food Hygienic Society of Japan, 2013, Volume: 54, Issue:6

    Two people out of three who accidentally ate boiled aconite leaves died in 2012. This was a typical case of aconite poisoning in Japan: Aconite (Aconitum spp.) was mistakenly collected instead of Anemone flaccida, an edible wild plant. The leaves of these plants are quite similar to each other. Chemical analyses of the aconite plant left at the scene suggested intake of a fatal amount of aconitine alkaloids by each person. The collector, who died, had missed the botanical differences between the two plants, even though he owned a wild plant guidebook. A. flaccida should be collected with its flowers in order to aid positive indentification and avoid aconite poisoning.

    Topics: Aconitine; Aconitum; Adult; Aged; Chromatography, High Pressure Liquid; Fatal Outcome; Female; Heart Arrest; Humans; Male; Middle Aged; Plant Leaves; Shock, Cardiogenic; Tachycardia, Ventricular; Tandem Mass Spectrometry

2013
Enhancement by Glycyrrhizae Radix of hepatic metabolism of hypaconitine, a major bioactive and toxic component of Aconiti Laterlis Radix, evaluated by HPLC-TQ-MS/MS analysis.
    Biomedical chromatography : BMC, 2013, Volume: 27, Issue:5

    Glycyrrhizae Radix (GR) is often prescribed together with Aconiti Laterlis Radix (ALR) (a so-called compatible drug pair) in traditional Chinese medicinal practice to reduce toxicity of ALR. However, the mechanisms involved remain to be addressed. In this study, the metabolic interactions between GR-ALR drug pair were investigated for the first time. First, an HPLC-TQ-MS/MS method was developed to analyze hypaconitine, a major bioactive and toxic component of ALR, in rat liver S9. Then the in vitro metabolic rates of hypaconitine by different rat liver S9 were compared using the established method. The experiments were designed in four groups: pure hypaconitine (group I) and ALR extract (group II) incubated with liver S9 of normal rats, and pure hypaconitine (group III) and ALR extract (group IV) incubated with liver S9 of GR-pretreated rats. When incubated for more than 4 h, the metabolic rates of hypaconitine in group III were significantly higher than those in group I, and when incubated for more than 2 h, the metabolic rates of hypaconitine in group IV were significantly higher than those in group II, suggesting that GR can enhance metabolic rate of hypaconitine, the mechanism of which might be related to hepatic metabolizing enzyme induction by GR.

    Topics: Aconitine; Aconitum; Animals; Chromatography, High Pressure Liquid; Drug Interactions; Drug Stability; Drugs, Chinese Herbal; Glycyrrhiza; Liver; Male; Methanol; Rats; Rats, Sprague-Dawley; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

2013
The role of efflux transporters on the transport of highly toxic aconitine, mesaconitine, hypaconitine, and their hydrolysates, as determined in cultured Caco-2 and transfected MDCKII cells.
    Toxicology letters, 2013, Feb-04, Volume: 216, Issue:2-3

    Aconitum alkaloids including aconitine (AC), mesaconitine (MA), hypaconitine (HA), are highly toxic. Their hydrolysates, such as benzoylaconine (BAC), benzoylmesaconine (BMA), benzoylhypaconine (BHA), aconine, and mesaconine, are considerably less toxic. Efflux transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein isoform 2 (MRP2), act as a first line of defence and play key roles in toxicity prevention. The aim of the present study was to determine the role of efflux transporters in the transport of Aconitum alkaloids using cultured Caco-2, MDR1-MDCKII and BCRP-MDCKII cells. Bidirectional transport assays of the Aconitum alkaloids were performed with or without P-gp (cyclosporine A and verapamil), BCRP (Ko143) and MRP2 (MK571) inhibitors. The efflux ratios (Er) of AC, MA, and HA in Caco-2 cells were 34.6±4.2, 29.7±2.1, and 15.6±2.1, respectively; those of BAC, BMA, and BHA were approximately 4, and those of aconine and mesaconine were equal to 1. The Er values of AC, MA, and HA in MDR1-MDCKII and BCRP-MDCKII cells were significantly higher than those in parental MDCKII cells. Taken together the results of Er values and intracellular amounts in the presence of inhibitors, P-gp and BCRP were involved in the transport of AC, MA and HA; and MRP2 might transport AC, MA, HA, BAC, BMA and BHA.

    Topics: Aconitine; Adenosine; Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Transport; Caco-2 Cells; Cyclosporine; Diketopiperazines; Dogs; Heterocyclic Compounds, 4 or More Rings; Humans; Intestinal Absorption; Madin Darby Canine Kidney Cells; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Propionates; Quinolines; Transfection; Verapamil

2013
Development and validation of a highly sensitive UPLC-MS/MS method for simultaneous determination of aconitine, mesaconitine, hypaconitine, and five of their metabolites in rat blood and its application to a pharmacokinetics study of aconitine, mesaconiti
    Xenobiotica; the fate of foreign compounds in biological systems, 2012, Volume: 42, Issue:6

    A rapid, specific and sensitive method was developed for the simultaneous determination of eight Aconitum alkaloids: aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA), benzoylhypaconine (BHA), aconine and mesaconine in rat blood by ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS). The UPLC-MS/MS system coupled with an electrospray ionization (ESI) source was operated in a positive mode via multiple-reaction monitoring (MRM). Samples were treated with methanol to remove protein prior to analysis by UPLC-MS/MS. The analytes were separated with a Waters C18 column (1.7 µm, 50 × 2.1 mm) and a gradient elution using acetonitrile and 0.1% formic acid-water as the mobile phases. The linear response range was from 0.125 to 1000 nmol/L for these eight alkaloids and the correlation coefficients (r(2) values) were all higher than 0.997. The method was validated with respect to precision, accuracy, recovery, matrix effect, carryover effect and sample stability, and found to be within the acceptable limits. The developed and validated method was successfully applied to simultaneously determine the eight Aconitum alkaloids in rats blood after intravenous administration of a mixture of AC, MA and HA.

    Topics: Aconitine; Alkaloids; Animals; Anti-Inflammatory Agents; Chromatography, High Pressure Liquid; Female; Male; Rats; Rats, Wistar; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

2012
Intestinal transport of pure diester-type alkaloids from an aconite extract across the Caco-2 cell monolayer model.
    Planta medica, 2012, Volume: 78, Issue:7

    Aconitine (AC), mesaconitine (MA), and hypaconitine (HA) are the active alkaloids identified in aconite tuber, an important traditional Chinese medicine. The study is aimed to investigate their intestinal transport profiles and potential interaction during the intestinal absorption using the Caco-2 cell monolayer model. All three alkaloids had good permeability with P(app) values greater than 1 × 10 (-6) cm · s (-1). However, AC, MA, and HA in a mixture and as an extract, in both cases with the same content of alkaloids, showed higher transport efficiency in the apical to basolateral, and lower transport efficiency in the basolateral to apical directions. Digoxin, as a P-glycoprotein (P-gp) substrate, was substantially effluxed in the basolateral to apical direction but inhibited by the three alkaloids. Furthermore, the backwards transport of MA and HA was inhibited by the P-gp inhibitor verapamil. These observations indicated that the three alkaloids may not only be P-gp inhibitors but also its substrates; they interact with each other and can potentially enhance their own bioavailability when taken concomitantly.

    Topics: Aconitine; Aconitum; Biological Availability; Biological Transport; Caco-2 Cells; Digoxin; Drug Interactions; Humans; Intestinal Absorption; Phytotherapy; Plant Extracts; Verapamil

2012
Preparation of Fe3O4 nanoparticle enclosure hydroxylated multi-walled carbon nanotubes for the determination of aconitines in human serum samples.
    Analytica chimica acta, 2012, Apr-29, Volume: 724

    A magnetic carbon nanomaterial for Fe(3)O(4) enclosure hydroxylated multi-walled carbon nanotubes (Fe(3)O(4)-EC-MWCNTs-OH) was prepared by the aggregating effect of Fe(3)O(4) nanoparticle on MWCNTs-OH, and combined with high-performance liquid chromatography (HPLC)/diode array detection (DAD) to determine the aconitines (aconitine, hypaconitine and mesaconitine) in human serum samples. Compared with other extraction modes investigated in experiment, Fe(3)O(4)-EC-MWCNTs-OH sorbents showed a good affinity to target analytes. Some important parameters that could influence extraction efficiency of aconitines, including the extraction mode, amounts of Fe(3)O(4)-EC-MWCNTs-OH, pH of sample solution, extraction time, desorption solvent and desorption time, were optimized. Under optimal conditions, the recoveries of spiked serum samples were between 98.0% and 103.0%; relative standard deviations (RSDs) ranged from 0.9% to 6.2%. The correlation coefficients varied from 0.9996 to 0.9998. The limits of detection ranged from 3.1 ng mL(-1) to 4.1 ng mL(-1) at a signal-to-noise ratio of 3. The experimental results showed that the proposed method was feasible for the analysis of aconitines in serum samples.

    Topics: Aconitine; Adsorption; Chromatography, High Pressure Liquid; Ferrosoferric Oxide; Humans; Hydrogen-Ion Concentration; Limit of Detection; Microscopy, Electron, Transmission; Nanoparticles; Nanotubes, Carbon; Serum; Signal-To-Noise Ratio; Solid Phase Extraction; Solvents

2012
Regeneratory characteristics of complex extract and isolated diterpene alkaloids of Aconitum baikalense.
    Bulletin of experimental biology and medicine, 2012, Volume: 152, Issue:4

    The effects of complex extract from Aconitum baikalense on reparative regeneration of a plane dorsal skin wound were studied. Treatment with Aconitum baikalense tincture stimulated reparation and skin regeneration. The effects of the Aconitum baikalense alkaloids on functional activity of fibroblast precursors were studied in vitro by cultural methods. Mesaconitine, hypaconitine, songorine, napelline, and 12-epinapelline N-oxide significantly stimulated the growth of colonies from fibroblast precursors. This indicated direct stimulation of fibroblasts by aconite alkaloids, which could be a mechanism of reparative activity of the complex extract.

    Topics: Aconitine; Aconitum; Alkaloids; Animals; Cell Proliferation; Cells, Cultured; Colony-Forming Units Assay; Female; Fibroblasts; Mice; Mice, Inbred CBA; Plant Components, Aerial; Plant Extracts; Regeneration; Skin; Wound Healing

2012
Identification and determination of Aconitum alkaloids in Aconitum herbs and Xiaohuoluo pill using UPLC-ESI-MS.
    Molecules (Basel, Switzerland), 2012, Aug-27, Volume: 17, Issue:9

    A rapid, specific, and sensitive ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) method to examine the chemical differences between Aconitum herbs and processed products has been developed and validated. Combined with chemometrics analysis of principal component analysis (PCA) and orthogonal projection to latent structural discriminate analysis, diester-diterpenoid and monoester-type alkaloids, especially the five alkaloids which contributed to the chemical distinction between Aconitum herbs and processed products, namely mesaconitine (MA), aconitine (AC), hypaconitine (HA), benzoylmesaconitine (BMA), and benzoylhypaconitine (BHA), were picked out. Further, the five alkaloids and benzoylaconitine (BAC) have been simultaneously determined in the Xiaohuoluo pill. Chromatographic separations were achieved on a C₁₈ column and peaks were detected by mass spectrometry in positive ion mode and selected ion recording (SIR) mode. In quantitative analysis, the six alkaloids showed good regression, (r) > 0.9984, within the test ranges. The lower limit quantifications (LLOQs) for MA, AC, HA, BMA, BAC, and BHA were 1.41, 1.20, 1.92, 4.28, 1.99 and 2.02 ng·mL⁻¹, respectively. Recoveries ranged from 99.7% to 101.7%. The validated method was applied successfully in the analysis of the six alkaloids from different samples, in which significant variations were revealed. Results indicated that the developed assay can be used as an appropriate quality control assay for Xiaohuoluo pill and other herbal preparations containing Aconitum roots.

    Topics: Aconitine; Aconitum; Alkaloids; Diterpenes; Drugs, Chinese Herbal; Plant Roots; Principal Component Analysis; Spectrometry, Mass, Electrospray Ionization

2012
Effect of hypaconitine combined with liquiritin on the expression of calmodulin and connexin43 in rat cardiac muscle in vivo.
    The Journal of pharmacy and pharmacology, 2012, Volume: 64, Issue:11

    To study the effects of hypaconitine used alone and combined with liquiritin on calmodulin (CaM) expression and connexin43 (Cx43) phosphorylation on serine368 (Ser368), as well as to investigate the intervention of liquiritin on these hypaconitine-induced effects.. Adult Wistar rats were orally administered hypaconitine (0.23, 0.69, 2.07 mg/kg per day), liquiritin (20 mg/kg per day), or hypaconitine (2.07 mg/kg per day) plus liquiritin (20 mg/kg per day) for seven consecutive days. The mRNA expression levels of CaM and Cx43 in rat myocardial tissue were determined by real-time quantitative PCR. The protein contents of CaM and phosphorylated Cx43 (Ser368) were determined by Western blot.. The results indicated that the mRNA and protein expression levels of CaM were significantly decreased by hypaconitine used alone and combined with liquiritin. Although CaM mRNA expression level was inhibited by liquiritin, its protein expression level was upregulated. Meanwhile, although no obvious effect on Cx43 mRNA expression was observed after the drug administration, the phosphorylation level of Cx43 (Ser368) was significantly inhibited. Furthermore, the coadministration of hypaconitine and liquiritin significantly reduced hypaconitine-induced inhibitory action on Cx43 (Ser368) phosphorylation.. The study indicated that hypaconitine could inhibit CaM expression and Cx43 (Ser368) phosphorylation, and liquiritin could interfere with this kind of effect by synergistically inhibiting CaM expression and by antagonizing Cx43 (Ser368) dephosphorylation induced by hypaconitine.

    Topics: Aconitine; Administration, Oral; Animals; Blotting, Western; Calmodulin; Connexin 43; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Flavanones; Gene Expression Regulation; Glucosides; Male; Myocardium; Phosphorylation; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA, Messenger

2012
Mechanisms of regeneratory effects of baikal aconite diterpene alkaloids.
    Bulletin of experimental biology and medicine, 2012, Volume: 153, Issue:6

    Regeneratory activities of Baikal aconite alkaloids were studied on the excision skin wound model. Manifest wound healing effects of songorine, napelline, and hypaconitine were detected. The therapeutic efficiency was based on activation of residual mesenchymal progenitor elements. The development of this phenomenon was explained by the direct effects of alkaloids on precursors and by higher production of growth factors by the skin stromal cells. Songorine exhibited the most pronounced specific activity due to more significant stimulation of progenitor cell differentiation associated with maximum activation of the secretory function of the microenvironment cells.

    Topics: Aconitine; Aconitum; Alkaloids; Animals; Animals, Outbred Strains; Cell Differentiation; Cellular Microenvironment; Diterpenes; Intercellular Signaling Peptides and Proteins; Male; Mesenchymal Stem Cells; Mice; Regeneration; Skin; Stromal Cells; Wound Healing; Wounds and Injuries

2012
Neutral fragment filtering for rapid identification of new diester-diterpenoid alkaloids in roots of Aconitum carmichaeli by ultra-high-pressure liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry.
    PloS one, 2012, Volume: 7, Issue:12

    A rapid and effective method was developed for separation and identification of diester-diterpenoid alkaloids (DDA) in the roots of Aconitum carmichaeli by ultra-high-pressure liquid chromatography coupled with high resolution LTQ-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS(n)). According to accurate mass measurement and the characteristic neutral loss filtering strategy, a total of 42 diester-diterpenoid alkaloids (DDA) were rapidly detected and characterized or tentatively identified. Meanwhile, the proposed fragmentation pathways and the major diagnostic fragment ions of aconitine, mesaconitine and hypaconitine were investigated to trace DDA derivatives in crude plant extracts. 23 potential new compounds were successfully screened and characterized in Aconitum carmichaeli, including 16 short chain fatty acyls DDA, 4 N-dealkyl DDA and several isomers of aconitine, mesaconitine and hypaconitine.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Diterpenes; Esters; Fatty Acids; Filtration; Isomerism; Plant Roots; Reference Standards; Tandem Mass Spectrometry

2012
Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid.
    European journal of pharmacology, 2011, Jan-25, Volume: 651, Issue:1-3

    Ulcerative colitis involves complicated etiology and presents diverse symptoms including intestine inflammation, bowel pain and diarrhea. Anti-inflammatory drugs are the mainstay in patient care, accompanied with antidiarrhea and analgesic agents used as symptomatic treatment. A classic traditional Chinese medicine formula, Fructus Mume pill (FMP), showed remarkable therapeutic efficacy in treating ulcerative colitis. However, since it contains many herbs and countless chemicals, the underlying mechanism is not clear. In this study, we selected three alkaloids from FMP, namely, berberine, hypaconitine and skimmianine to study the individual drug effect and compare these results with the BHS combination on: 1) The recovery of ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. 2) Mice with xylene-induced acute exudative edema and acetic acid-induced writhing. 3) Gastrointestinal transit inhibition, and 4) the response of HT29 cells after treatment with lipopolysaccharide. We found that the compound hypaconitine showed a potent analgesic effect, while skimmianine acted as an antidiarrhea agent and the component berberine was the key agent exerting anti-inflammatory effect. However, since berberine killed the commensal bacteria and induced lipopolysaccharide release, it could at the same time aggravate colon inflammation. The three-alkaloid combination BHS produced complementary and synergistic effects in colon inflammation recovery, relieving acetic acid-induced bowel pain and xylene-induced acute exudative edema. BHS also decreased lipopolysaccharide production and enhanced the therapeutic efficacy. It is hoped that this study will lay the foundation to further dissect and understand the FMP formula to improve the treatment with simplified and well defined drug combinations for this dreadful disease.

    Topics: Acetic Acid; Aconitine; Alkaloids; Analgesics; Animals; Antidiarrheals; Behavior, Animal; Berberine; Colitis, Ulcerative; Colon; Drug Evaluation, Preclinical; Drug Synergism; Edema; Epithelial Cells; Gastrointestinal Transit; HT29 Cells; Humans; Inflammation; Male; Mice; NF-kappa B; Prunus; Quinolines; Rats; Toll-Like Receptor 4; Trinitrobenzenesulfonic Acid; Xylenes

2011
Effect of (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate on transdermal delivery of Aconitum alkaloids.
    Drug development and industrial pharmacy, 2011, Volume: 37, Issue:3

    The aim of this work was to evaluate the percutaneous absorption of Aconitum alkaloids using (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate (M-OA) as an enhancer as well as to investigate the effect of M-OA in isopropyl palmitate (IPP) solution (5% ethanol in IPP, w/v), with or without an enhancer, on the stratum corneum (SC) barrier properties in vitro.. The in vitro permeation studies of Aconitum alkaloids were conducted in isopropyl myristate (IPM) solution in side-by-side diffusion cells. In addition, scanning electron microscopy (SEM) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the M-OA biophysical changes in SC barrier function in vitro.. The in vitro permeation studies indicated that M-OA had significant enhancing effect on the permeation of mesaconitine (MA) and hypaconitine (HA); however, aconitine (AC) was too low to be detected on the receiver side, and L-menthol had no effect on the penetration of all the Aconitum alkaloids. Morphological changes in the skin after enhancer treatment demonstrated that the extraction of the SC lipids by the enhancers led to disruption of the SC and the desquamation of SC flake. ATR-FTIR spectra of C-H asymmetric/symmetric stretching peak shifts and amide II stretching vibrations were indicative of SC lipid fluidization and changes in protein conformation, respectively.. The results showed that M-OA was worthy of further investigation as a potential candidate for inclusion in transdermal formulations as a penetration enhancer.

    Topics: Aconitine; Aconitum; Administration, Cutaneous; Animals; Excipients; Lipids; Male; Oleic Acids; Permeability; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility

2011
Microsomal cytochrome P450-mediated metabolism of hypaconitine, an active and highly toxic constituent derived from Aconitum species.
    Toxicology letters, 2011, Jul-04, Volume: 204, Issue:1

    Hypaconitine (HA), an active and highly toxic constituent derived from Aconitum species, is widely used to treat rheumatism. Little is known about the hepatic cytochrome P450-catalyzed metabolism of HA. The present study investigated the metabolism of HA in vitro using male human liver microsomes (MHLMS). Chemical inhibitors of specific CYP enzymes, CYP-specific inhibitory monoclonal antibodies (mAbs), and cDNA-expressed CYP enzymes were used to confirm the enzyme subtypes involved in the metabolism. Liquid chromatography-high resolution mass spectrometry (LC-MS) was used to detect and identify metabolites. A total of 11 metabolites were identified in MHLMS incubations. The major metabolic pathways included demethylation (M1-M3), demethylation-dehydrogenation (M4-M6), hydroxylation (M7, M8), and didemethylation (M9-M11). M8 was identified as mesaconitine (MA), another active and highly toxic constituent of Aconitum. The results of chemical inhibition, monoclonal antibody inhibition, and cDNA-expressed CYP enzyme studies showed that the primary contributors toward HA metabolism were CYP3A4 and 3A5, with secondary contributions by CYP2C19, 2D6, and CYP2E1. CYP1A2 and 2C8 provided minor contributions.

    Topics: Aconitine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Gas Chromatography-Mass Spectrometry; Humans; Hydroxylation; Microsomes, Liver

2011
CE-electrochemiluminescence with ionic liquid for the facile separation and determination of diester-diterpenoid aconitum alkaloids in traditional Chinese herbal medicine.
    Electrophoresis, 2011, Volume: 32, Issue:12

    A CE-electrochemiluminescence(CE-ECL) detection system, CE/tris(2,2'-bipyridyl) ruthenium(II)ECL with ionic liquid, was established for the determination of diester-diterpenoid aconitum alkaloids (aconitine (AC), mesaconitine (MA) and hypaconitine (HA)) in traditional Chinese herbal medicine. Running buffer containing 25 mM borax-20 mM 1-ethyl-3-methylimidazolium tetrafluoroborate at pH 9.15 was used, which resulted in significant changes in separation and obvious enhancement in ECL intensity for AC, MA and HA with similar structures. End-column detection was achieved in 50 mM phosphate buffer with 5 mM Ru(bpy)₃²⁺ (pH 9.15) at applied detection voltage of 1.20 V when the distance between the Pt working electrode and outlet of capillary (50 cm × 25 μm id) was set at 150 μm. One single quantitative analysis of three alkaloids was achieved at a separation voltage of 15 kV within 10 min. Moreover, two extraction processes (ethanol extraction and ethyl ether extraction after basification) were investigated. The result showed that ethanol extraction process has higher extraction efficiency than ethyl ether extraction process. Under the optimized conditions, the detection limits of AC, MA and HA were 5.62 × 10(-8) , 2.78 × 10(-8) and 3.50 × 10(-9) mol/L (S/N=3), respectively. The method was successfully applied to determine the amounts of AC, MA and HA in the aconitum herbal samples.

    Topics: Aconitine; Aconitum; Drugs, Chinese Herbal; Electrophoresis, Capillary; Ethanol; Ether; Hydrogen-Ion Concentration; Ionic Liquids; Linear Models; Luminescent Measurements; Reproducibility of Results; Sensitivity and Specificity

2011
[Comparison of intracorporal absorption of hypaconitine in Heishunpian decoction and its compound recipe decoction by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry].
    Se pu = Chinese journal of chromatography, 2011, Volume: 29, Issue:5

    An ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was developed for the determination of hypaconitine in the plasma of the rats administered with Heishunpian (HSP) decoction, Zhufu (ZF) decoction and Gancaofuzi (GF) decoction, separately. Hypaconitine and the internal standard were separated on a ZORBAX Extend-C18 column. The concentration-time curve of hypaconitine in the plasma was protracted, and pharmacokinetic parameters were calculated, then the pharmacokinetic comparison of hypaconitine between HSP, ZF and GF was carried out for the first time. The results of the methodological test showed that the plasma concentration of hypaconitine presented good linear relationship in the range of 0.02-10 ng/mL. The results of the sample determination showed that the absorptive degree of ñfrom ZF decoction in the plasma was lower than that from HSP decoction, while the absorptive degree of hypaconitine from GF decoction in plasma was higher than that from HSP decoction. It was deduced that some components in ZF decoction can restrain the absorption of hypaconitine in plasma, and some components in GF decoction may promote the absorption of hypaconitine in plasma, and the difference in drug effects between ZF decoction and GF decoction may derive from the different absorptive degrees of hypaconitine in plasma. The pharmacokinetic property of hypaconitine was proposed to be non-linear dynamics on the basis of the drug elimination half life (T(1/2)) and the area under the plasma concentration-time curve (AUC).

    Topics: Absorption; Aconitine; Aconitum; Animals; Chromatography, High Pressure Liquid; Drug Compounding; Drugs, Chinese Herbal; Female; Male; Mass Spectrometry; Rats

2011
[Isolation and structure identification of C19 diterpenoid alkaloids from Aconitum carmichaeli by high-speed counter-current chromatography].
    Se pu = Chinese journal of chromatography, 2011, Volume: 29, Issue:5

    Three C19 diterpenoid alkaloids were isolated and purified from the lateral roots of Aconitum carmichaeli Debx. (Fuzi in Chinese) by high-speed counter-current chromatography (HSCCC). A mixture of n-hexane-ethyl acetate-methanol-water (3:5:4:5, v/v/v/v) was used as the two phase solvent system. The lower phase was used as the mobile phase and was operated at a flow rate of 2.0 mL/min, while the apparatus was rotated at 850 r/min, and the detection wavelength was at 235 nm. Under these conditions, 15.3 mg of beiwutine, 35.1 mg of mesaconitine and 22.7 mg of hypaconitine were obtained from 90 mg of crude extract in one-step separation with the purities of 97.9%, 96.2% and 99.2%, respectively, determined by high performance liquid chromatography. The structures of these three compounds were identified by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H-NMR) and 13C-NMR. The results indicate that HSCCC is a powerful technique for the purification of diterpenoid alkaloids from the lateral roots of Aconitum carmichaeli Debx.

    Topics: Aconitine; Aconitum; Alkaloids; Countercurrent Distribution; Diterpenes; Drugs, Chinese Herbal

2011
[The effect of the compatibility of Radix Aconiti Laterlis and radix glycyrrhizae on pharmacokinatic of aconitine, mesaconitine and hypacmitine in rat plasma].
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2011, Volume: 34, Issue:6

    To established an HPLC-MS assay to determine aconitine, mesaconitine and hypaconitine simultaneously in rat plasma and be used to investigate the pharmacokinetics of the three alkaloids.. Three groups of rats were orally administered respectively with three decoctions including decoction of Radix Aconiti Laterlis, blend decoction of Radix Aconiti Laterlis and Radix Glycyrrhizae which decocted separately, decoction of Radix Aconiti Laterlis and Radix Glycyrrhizae which decocted together,the dosage of Radix Aconiti Laterlis was 1.5 g/kg. The contents of aconitine, mesaconitine and hypaconitine in rat plasma were detected using a liquid Chromatography-electrospray ionization/tandem mass spectrometry method. Pharmacokinetic parameters were estimated using DAS 2.0.. The pharmacokinetic parameters of the three compounds obtained showed that Cmax and AUC of aconitine, mesaconitine and hypaconitine were decreased. MRT, t1/2 were prolonged and there was no obviously change in Tmax when Radix Aconiti Lateralis was combined with Radix Glycyrrhizae. The effect of decoction which decocted together was more prominent than which decocted separately.. There are obvious effects on pharmacokinetic of Aconitine, Mesaconitine and Hypaconitine in Rat Plasma when Radix Aconiti Laterlis is combined with Radix Glycyrrhizae.

    Topics: Aconitine; Aconitum; Administration, Oral; Animals; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glycyrrhiza; Male; Mass Spectrometry; Pharmacokinetics; Plant Roots; Plants, Medicinal; Rats

2011
[UPLC-TOF/MS based chemical profiling approach to evaluate toxicity-attenuated chemical composition in combination of ginseng and radix aconiti praeparata].
    Yao xue xue bao = Acta pharmaceutica Sinica, 2011, Volume: 46, Issue:12

    In the present study, an ultra performance liquid chromatography coupled with time-of-fight mass spectrometry (UPLC-TOF/MS) based chemical profiling approach was used to evaluate chemical constitution between co-decoction and mixed decoction of ginseng and Radix Aconiti Praeparata. Two different kinds of decoctions, namely co-decoction of ginseng and Radix Aconiti Praeparata: water extract of mixed two herbs, and mixed decoction of ginseng and Radix Aconiti Praeparata: mixed water extract of each individual herbs, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC-TOF/MS analysis. The datasets of t(R) m/z pairs, ion intensities and sample codes were processed with supervised partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between these two decoction samples. Significant difference between the two decoction samples was showed in the results of positive ion mode. The contents of hypaconitine and deoxyaconitine decreased, while that of benzoylmesaconine, benzoylhypaconine and dehydrated benzoylmesaconine increased in the samples of co-decoction of ginseng and Radix Aconiti Praeparata. The content of diester-diterpenoid alkaloids decreased, while that of monoester-diterpenoid alkaloids increased, which is probably the basis of toxicity-attenuated action when combined ginseng with Radix Aconiti Praeparata.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Panax; Plants, Medicinal; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

2011
[Determination of content changes of three diester-diterpenoid alkaloids in compatibility of radix aconiti laterlis preparata and Rhizoma pinelliae, Fructus trichosanthis, Bulbus fritillariae, Radix ampelopsis, Rhizoma bletillae by HPLC].
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2011, Volume: 34, Issue:12

    To analyze the three diester-alkaloids content in the decoctions before and after Radix aconiti lateralis preparata combined with Rhizoma pinelliae, Fructus trichosanthis, Bulbus fritillariae, Radix ampelopsis, Rhizoma bletillae, respectively.. HPLC analysis was performed on a Agilent Extend C18 column,eluted with a mobile phase consisted of acetonitrile/methanol - 35 mmol/L ammonium acetate and gradient elution,with a flow rate of 0.6 ml/min and the detection wavelength of 235 nm.. The contents of three diester-alkaloids in the co-decoctions of Radix aconiti laterlis preparata combined with Rhizoma pinelliae, Fructus trichosanthis, Bulbus fritillariae, Rhizoma bletillae were more than that of single Radix aconiti laterlis preparata decoction, expect the Bulbus fritillariae cirrhosae,Radix ampelopsis and Rhizoma pinelliae praeparatum. From the result,we can found that the content of three diester-alkaloids in decoctions was correlated with the decoction pH.. The pH of decoction is one of the most important factors to relate the three diester-alkaloids content in the decoctions.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Fritillaria; Hot Temperature; Hydrogen-Ion Concentration; Orchidaceae; Pinellia; Plant Roots; Plants, Medicinal; Reproducibility of Results; Trichosanthes; Vitaceae

2011
[Extraction technology of diester-type alkaloids from Radix Aconiti lateralis].
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2011, Volume: 34, Issue:11

    To determine the suitable extraction technology of diester-type alkaloids, such as mesaconitine, aconitine and hypaconitine from the roots of Aconitum carmichaeli (Radix Aconiti lateralis).. The contents of mesaconitine, aconitine and hypaconitine were determined by HPLC. Single-factor experiment was used to study the extraction factors.. The suitable extraction technology for diester-type alkaloids was as follows: coarse sizings of Radix Aconiti lateralis was extracted by 10 times ethanol for 3 times (each time for 1 day) at 15 degrees C. The total yield of diester-type alkaloids was 0.57%, including 0.16% aconitine, 0.032% mesaconitine and 0.38% hypaconitine, and the purity was 18.81%.. The extraction technology is efficient, harmfulless, economical, convenient and can be used for industrial production.

    Topics: Aconitine; Aconitum; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Ethanol; Plant Roots; Plants, Medicinal; Technology, Pharmaceutical; Temperature; Time Factors

2011
[Evaluation of the accumulation of dry substance and active componentsevaluation of the accumulation of dry substance and active components of Radix Aconiti Lateralis Praeparata].
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2010, Volume: 33, Issue:4

    To study the accumulation rules of dry substance and active components in the Radix Aconiti Lateralis Praeparata for providing the basic evidences to collection time.. The Roots were collected periodically and their fresh weight and dry weight were measured. The contents of total alkaloids and three diester aconitum alkaloids aconitine, hypaconitine and mesaconitine were determined by titration and HPLC respectively.. During the stage of root inflation, the content of total alkaloids was at a certain level, while the content of diester aconitum alkaloids were increased gradually. The total amount of alkaloid and diester aconitom alkaloids were increased rapidly from the last third of April to the middle third of June, and then maintained at relative constant levels and were decreased from the first third of July.. It is more preferable to collect the Radix Aconiti Lateralis Praeparata during the period from the last third of June to first third of July.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Plant Roots; Quality Control; Seasons

2010
Determination of aconitine, hypaconitine and mesaconitine in urine using hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2010, Oct-15, Volume: 878, Issue:28

    Hollow fiber liquid-phase microextraction (HF-LPME) coupled with high-performance liquid chromatography was used to simultaneously determine three Aconitum alkaloids, including aconitine (AC), hypaconitine (HA) and mesaconitine (MA) in human urine sample. Analytes were extracted from 5mL urine sample containing 1.0mmol/L NaOH into 1-octanol membrane phase impregnated in the pores of hollow fiber wall, and then back extracted into acidified aqueous solution in the lumen of the hollow fiber. After extraction, 10μL of the acceptor phase was analyzed directly by HPLC. In this method, some important extraction parameters, such as organic solvent, extraction time, stirring rate, pH of donor phase and acceptor phase, temperature, and the volume of acceptor phase were optimized. This method provided 98- to 288-fold enrichment factors within 60min of extraction and good repeatability with RSDs of 0.99-7.22%. The calibration curves were linear over the ranges of 16.0-128.0μg/L for AC, 11.0-88.0μg/L for HA and 8.1-64.8μg/L for MA in human urine sample, with correlation coefficients of 0.9949, 0.9969 and 0.9904, respectively. Limits of detection were from 0.7 to 1.5μg/L, and recoveries from spiked urine sample varied from 84.4% to 106.2% for AC, 77.3% to 85.6% for HA and 90.1% to 100.8% for MA.

    Topics: Aconitine; Aconitum; Alkaloids; Chemical Fractionation; Chromatography, High Pressure Liquid; Humans; Hydrogen-Ion Concentration; Linear Models; Reproducibility of Results; Sensitivity and Specificity; Temperature

2010
[Difference of hypaconitine concentration in serum between cold-deficiency and normal mice].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2010, Volume: 35, Issue:15

    To investigate the difference of hypaconitine concentration in serum between normal and cold-deficiency mice after administration of aconite decoction. To analyze how the toxic dose of aconite decoction correlate to the metabolic environment.. Prepared cold-deficiency mice model, treated normal and cold-deficiency mice with aconite decoction for 14 days continuously, and then detected hypaconitine concentration in serum by HPLC along with survival ratio of mice on the first, seventh and fourteenth day.. After administration of aconite decoction for 14 days, the hypaconitine concentration in serum of cold-deficiency mice is close to that in normal mice. It showed aconite decoction has the ability of regulating metabolism environment, the hypaconitine concentration in serum of normal mice was higher on the seventh and fourteenth day than that on first day. It showed that aconite decoction can disturb metabolism environment of normal mice. It was also been observed that the range of variation of hypaconitine concentration in cold-deficiency mice was minor than that in normal mice during the fourteen days' administration.. The difference of serum concentration in normal and cold-deficiency mice showed that there were different metabolic environments in two mice models, and the metabolic environment changed during administration. These results showed that the different toxic doses of aconite decoction were partially due to the different metabolic environments.

    Topics: Aconitine; Aconitum; Animals; Cold Temperature; Drugs, Chinese Herbal; Male; Mice; Mice, Inbred ICR

2010
[Analysis of chemical composition in the combination of monkshood and pinellia by UPLC/Q-TOFMS with multivariate statistical analysis].
    Yao xue xue bao = Acta pharmaceutica Sinica, 2010, Volume: 45, Issue:10

    In the present study, an ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/Q-TOFMS) based on chemical profiling approach to evaluate chemical constitution between mixed decoction and co-decoction of monkshood-pinellia combination of the eighteen incompatible medications (Shi Ba Fan) was proposed. Two different kinds of decoctions, namely monkshood-pinellia co-decoction: water extract of the two herbs together, and monkshood-pinellia mixed decoction: water extract of each individual herbs mixed together, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC/Q-TOFMS analysis, the datasets were processed with MassLynx 4.1 to holistically compare the difference between these two kinds of decoction samples. The most changed components during decocting were analyzed. Using the proposed approach, global chemical difference was found between co-decoction and mixed decoction, mesaconitine, aconitine and hypaconitine were identified as the most changed components (changed most significantly) during decocting. Result shows significant difference between two kinds of decoction samples, and the significant differences are probably related to the incompatibility of monkshood and pinellia.

    Topics: Aconitine; Aconitum; Chromatography, High Pressure Liquid; Drug Combinations; Drug Incompatibility; Multivariate Analysis; Pinellia; Plant Roots; Plant Tubers; Plants, Medicinal; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

2010
[Determination of aconitine and hypaconitine in Gucixiaotong Ye by capillary electrophoresis with field-amplified sample injection].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2010, Volume: 35, Issue:24

    To set up a capillary electrophoresis method with field-amplified sample injection for the determination f aconitine and hypaconitine in Gucixiaotong Ye.. An uncoated fused-silica capillary column (50 microm x 50 cm, effective length 42 cm) was used as the separation channel. The running buffer was 50 mmol x L(-1) phosphate electrolyte solution (pH 9)-m nol (90:10) , the running voltage was 10 kV and the capillary inlet was dipped in methanol for 5 s prior to electrokinetic injection (12 kV, 30 s), the detection wavelength was set at 235 nm.. Aconitine and hypaconitine were linear in the concentration ranges of 17.2-275 microg x L(-1) and 34. 4-550 microg x L(-1), respectively. The average recovery was more than 93.9% with the RSD of 3.8%. This method could enrich 500 fold of aconitine alkaloid.. The method is simple, rapid and specific with high stacking efficiency, it provides a new reliable means for production and quality control of Gucixiaotong Ye.

    Topics: Aconitine; Buffers; Electricity; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Injections; Solutions; Time Factors

2010
Application of experimental design and radial basis function neural network to the separation and determination of active components in traditional Chinese medicines by capillary electrophoresis.
    Analytica chimica acta, 2009, Apr-06, Volume: 638, Issue:1

    Orthogonal design has been used to the optimization of separation and determination of two active components in traditional Chinese medicines by capillary electrophoresis. The concentration of phosphate, applied voltage, organic modifier content and buffer pH were selected as variable parameters. Their different effects on peak resolution were studied by the experimental design method. Optimized separation conditions were obtained and successfully applied to the separation and determination of aconitine and hypaconitine in Aconitum medicinal herbs. Good separation was achieved within 7 min using a buffer system composed of 20 mmol L(-1) phosphate and 35% acetonitrile at pH 9.5. The applied voltage was 14 kV and the detection was set at 235 nm. In addition, a radial basis function neural network with a "4-18-1" structure was developed based on the experimental results of orthogonal design and uniform design, and was applied to the prediction of peak resolution of the two active components under the optimum separation conditions given by orthogonal design. The predicted results were in good agreement with the experimental values, indicating that radial basis function neural network is a potential way for the selection of separation conditions in capillary electrophoresis.

    Topics: Aconitine; Aconitum; Algorithms; Drugs, Chinese Herbal; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Neural Networks, Computer; Plant Extracts; Research Design; Solvents

2009
Metabolomic analysis of biofluids from rats treated with Aconitum alkaloids using nuclear magnetic resonance and gas chromatography/time-of-flight mass spectrometry.
    Analytical biochemistry, 2009, Dec-15, Volume: 395, Issue:2

    The Aconitum alkaloids aconitine, mesaconitine, and hypaconitine are the main toxic components in a commonly used traditional Chinese herbal medicine Fu Zi. To provide guidelines for the safe use of this medicine, metabolic changes in Wistar rats caused by these compounds were investigated by means of integrated analysis of two metabonomic approaches: (1)H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). Rats were given a single dose of aconitine, mesaconitine, hypaconitine, or vehicle. The largest metabolic changes were observed 6 h after treatment. Every group receiving a dose had higher urine concentrations of glucose, acetate, dimethylglycine, succinate, and alanine and had lower concentrations of creatinine, citrate, 2-oxoglutarate, N-acetylated metabolites, and trimethylamine-N-oxide (TMAO) than did the control group. These results may reflect the perturbation of renal tubular function within the first 24 h after treatment. The results also revealed a larger perturbation of metabolic profiles in the aconitine group than in the mesaconitine and hypaconitine groups, illustrating how these alkaloids exhibit different toxicities. An analysis of plasma samples collected 7 days postdose showed that there were higher levels of lactate, alanine, and lipids along with lower levels of glucose, beta-hydroxybutyrate, and creatine in the plasma of the aconitine and mesaconitine groups than there were in the control and hypaconitine groups. The GC/TOF-MS data from the plasma samples showed that the number of metabolites, with significant changes or with a tendency to change, in the aconitine and mesaconitine groups were dissimilar, suggesting a possible difference in the acute toxicity mechanisms of these alkaloids.

    Topics: Aconitine; Aconitum; Alkaloids; Animals; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Metabolome; Metabolomics; Nuclear Magnetic Resonance, Biomolecular; Rats; Rats, Wistar; Time Factors; Urinalysis

2009
[Changes of DDAs content affected by different processing time and its relationship with safety of processed Fuzi].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2009, Volume: 34, Issue:9

    To study the correlation between content changes of Diester diterpenoid alkaloids (DDAs) content and safety of the processed Fuzi.. Sequential and Bliss methods were used to evaluate the safety of 7 kinds of Fuzi processed with different processing time. The relationship between ED50, TD50, TI and content changes of DDAs of those processed Fuzi was studied, the correlation between the content changes and effect of different processed Fuzi was analyzed, and the toxicity of those processed Fuzi with multiple linear regression was tested.. Fuzi with good efficiency and safety contains proper hypaconitine (HA) and mesaconitine (MA). Aconitine (AC) interfered efficacy of Fuzi (negative correlation), HA showed positive correlation with toxicity and efficacy of Fuzi.. HA and MA kept in determinate proportion are very important for the safety and effectivity of processed Fuzi.

    Topics: Aconitine; Alkaloids; Animals; Diterpenes; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Magnoliopsida; Male; Rats; Time Factors

2009
[Distribution of aconitum alkaloids in the corpse died of acute aconite intoxication].
    Fa yi xue za zhi, 2009, Volume: 25, Issue:3

    To investigate the distribution of aconite alkaloids in biological fluids and tissues in the corpse died of acute aconite intoxication and to provide information for sample selection and result evaluation in forensic identification.. The content of aconite alkaloids in biological fluids and tissues were determined by liquid chromatography-tandem mass spectrometry.. The content of aconite displayed in decending order of urine, bile, gastric content, heart blood, pancreas, heart, intestine, liver, kidney, stomach, lung, gallbladder and spleen, with no aconite detected in the brain.. It was indicated that urine, bile and blood are the best specimens for the determination of aconite in body of the acute aconite intoxication.

    Topics: Aconitine; Aconitum; Acute Disease; Bile; Chromatography, Liquid; Drugs, Chinese Herbal; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Gastric Mucosa; Humans; Liver; Male; Middle Aged; Tissue Distribution

2009
Simultaneous quantitation of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetics evaluation of "SHEN-FU" injectable powder.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2008, Oct-01, Volume: 873, Issue:2

    A rapid, specific and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids, i.e. aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA) in human plasma collected from 18 healthy volunteers after intravenous drop infusion of "SHEN-FU" injectable powder in three different dosages. Lappaconitine was selected as the internal standard (IS). LC/MS/MS system coupled with an electrospray ionization (ESI) source was performed in multiple-reaction monitoring (MRM) mode. The transitions of the Aconitum alkaloids executed as following: m/z 646.3-->586.0 for AC; m/z 632.4-->573.1 for MA; m/z 616.2-->556.1 for HA; m/z 604.2-->104.8 for BAC; m/z 590.1-->104.8 for BMA; m/z 574.1-->104.8 for BHA; m/z 585.2-->161.8 for IS. Sample preparation was performed with solid-phase extraction (SPE) on a 1 mL HLB cartridge prior to analysis. The separation was applied on a Waters C(18) column (1.7 microm, 2.1 mm x 100 mm) and a gradient elution of methanol and 0.1% formic acid-water was used as mobile phase. The retention time was less than 4.5 min. The concentrations ranged from 0.1 to 1000 ng/mL for all six Aconitum alkaloids and showed a good linearity with the correlation coefficient (r(2)) >0.995. The validated method was employed to simultaneous quantitation and successfully used for the first time for the pharmacokinetic evaluation of the six Aconitum alkaloids after intravenous drop administration of "SHEN-FU" injectable powder in phase I clinical trial.

    Topics: Aconitine; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Sensitivity and Specificity; Tandem Mass Spectrometry

2008
A new norditerpenoid alkaloid from Aconitum taipaicum.
    Yao xue xue bao = Acta pharmaceutica Sinica, 2008, Volume: 43, Issue:9

    To investigate the chemical constituents of the roots of Aconitum taipaicum, silica gel column chromatography was used for the isolation and purification of compounds. A new norditerpenoid alkaloid, isodelelatine (1), along with five known alkaloids, atisine (2), delfissinol (3), liangshanine (4), hypaconitine (5) and delelatine (6) were isolated and identified. The structure of the new compound was elucidated on the basis of spectral data.

    Topics: Aconitine; Aconitum; Alkaloids; Diterpenes; Molecular Structure; Plant Roots; Plants, Medicinal

2008
[Simultaneous determination of aconitine analogues in Aconitum plants and foods that caused food poisoning by liquid chromatography with tandem mass spectrometry].
    Shokuhin eiseigaku zasshi. Journal of the Food Hygienic Society of Japan, 2008, Volume: 49, Issue:2

    A simple method for the simultaneous determination of four aconitine analogues (AC; aconitine, HA; hypaconitine, MA; mesaconitine, JA; jesaconitine) in Aconitum plants (Aconitum subcuneatum NAKAI) and a food that caused food poisoning was developed, using liquid chromatography tandem mass spectrometry (LC/MS/MS). Aconitine analogues were extracted with 1 mmol/L HCl and then cleaned up with an Oasis HLB cartridge. The LC separation was performed with an octadecylated silica column (Develosil ODS-HG-5, 2.0 mm i.d. x 50 mm) at a flow rate of 0.2 mL/min, using A solution (5 mmol/L ammonium acetate dissolved in 0.1% acetic acid) and B solution (acetonitrile-THF=1 : 3), 90%A (0 min)-->60%A (15 min)-->const. (2 min). Mass spectral acquisition was performed in the positive mode and the analogues were targeted using multiple reaction monitoring (MRM) with electrospray ionization (ESI). The recoveries of aconitine analogues were 93-99% from Aconitum plants. The detection limits of AC, HA, MA and JA were 0.4, 0.4, 0.3 and 0.5 ng/g, respectively. The aconitine analogues, except JA, were detected in food that caused food poisoning at the level of 2.6-29.7 microg/g. These results indicate that the developed method is suitable for the determination of aconitine analogues in Aconitum plants and foods that cause food poisoning.

    Topics: Aconitine; Aconitum; Chromatography, Liquid; Food Analysis; Foodborne Diseases; Tandem Mass Spectrometry

2008
Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.
    Journal of ethnopharmacology, 2006, Feb-20, Volume: 103, Issue:3

    Processed Aconiti tuber (PAT) is a herbal medicine that has been widely used as an analgesic since ancient times. We investigated effects of subanalgesic doses of PAT on morphine tolerance in mice. Mice received subcutaneous morphine (10 mg/kg) and oral PAT at subanalgesic doses (0.1 or 0.3 g/kg), once a day for 7 days. Mechanical nociceptive thresholds were measured using the tail pressure test, at 60 min after the daily s.c. morphine injections. In the placebo-treated group, repeated administration of s.c. morphine resulted in development of analgesic tolerance. In the PAT-treated groups, oral PAT attenuated morphine tolerance, dose-dependently. The main ingredient alkaloid of PAT causing its tolerance-attenuating activity was mesaconitine, but other ingredient alkaloids, such as aconitine and hypaconitine, also contributed to this activity. In addition, repeated treatment with PAT could reverse already-developed morphine tolerance. Subanalgesic doses of oral PAT thus can attenuate and reverse morphine tolerance in mice.

    Topics: Aconitine; Aconitum; Alkaloids; Analgesics; Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Drug Tolerance; Drugs, Chinese Herbal; Male; Mice; Morphine; Pain; Pain Measurement; Pain Threshold; Plant Tubers; Time Factors

2006
Quantitative determination of diterpenoid alkaloids in four species of Aconitum by HPLC.
    Journal of pharmaceutical and biomedical analysis, 2006, Mar-03, Volume: 40, Issue:4

    A high performance liquid chromatography (HPLC) method has been developed for the determination of five principal alkaloids (benzoylmesaconine, mesaconitine, aconitine, hypaconitine and deoxyaconitine) found in four species of genus Aconitum. The five alkaloids were analyzed simultaneously with an XTerraRP18 column by gradient elution using 0.03 M ammonium hydrogen carbonate-acetonitrile as mobile phase. The recovery of the method was 94.6-101.9%, and all the alkaloids showed good linearity (gamma = 0.9999) in a relatively wide concentration range. The results indicated that contents of alkaloids in Aconitum varied significantly from species to species; hence quality control of Aconitum drugs is very necessary.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Diterpenes; Drugs, Chinese Herbal; Plant Roots; Regression Analysis; Reproducibility of Results

2006
Sensitive analysis of aconitine, hypaconitine, mesaconitine and jesaconitine in human body fluids and Aconitum tubers by LC/ESI-TOF-MS.
    Journal of mass spectrometry : JMS, 2006, Volume: 41, Issue:6

    The Aconitum species (Ranunculaceae) are widely distributed in northern Asia and North America. Their roots are popularly used in herbal medicines in China and Japan. Many cases of accidental, suicidal and homicidal intoxication with this plant have been reported; some of these were fatal because the toxicity of Aconitum is very high. It is thus important to detect and quantify Aconitum alkaloids in body fluids, with high sensitivity. We have developed a simple and sensitive method for measuring four kinds of Aconitum alkaloids (aconitine, hypaconitine, jesaconitine and mesaconitine) by LC/electrospray (ESI)-time-of-flight (TOF)-MS. For all of them, only molecular ions were observed at an orifice voltage of 75 V; at 135 V, base peaks corresponding to [M - 60 + H]+ ions were observed. These four compounds and methyllycaconitine (internal standard) in human plasma samples were purified by solid-phase extraction. The four extracted compounds were completely separated in mass chromatograms; the calibration curves showed good linearity in the range 10-300 ng/ml, and the detection limits were estimated to be 0.2-0.5 ng/ml. Using our method, we also determined the amounts of these compounds in tuber samples. The present method is applicable in clinical and forensic toxicology.

    Topics: Aconitine; Aconitum; Blood Chemical Analysis; Chromatography, High Pressure Liquid; Humans; Plant Tubers; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

2006
[Determination of three kind of diester diterpenoid alkaloids (DDAs) in Aconitum carmichaeli and its processed products by HPLC].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2006, Volume: 31, Issue:14

    To establish an HPLC method for the determination of three kind of diester diterpenoid alkaloids (DDAs) in Aconitum carmichaeli and its processed products namely mesaconitine, aconitine and hypaconitine.. A Zorbax Eclipse XDB C18 column was used, and ammonium acetate solution-acetonitrile as the mobile phase, with a flow rate of 1.0 mL x min(-1) and a detection wavelength of 230 nm.. Mesaconitine, aconitine and hypaconitine, were separated, and the calibration curves of them were in good linearity over the range of 0.035 7-1.784 microg (r = 0.9999), 0.0126-0.632 microg (r = 0.9997) and 0.0334-1.672 microg (r = 0.9997) respectively.. This method is simple and accurate. It can be used in the identification and quality control of A. carmichaeli.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Hot Temperature; Plant Roots; Plants, Medicinal; Quality Control; Reproducibility of Results; Technology, Pharmaceutical

2006
Tissue distribution of Aconitum alkaloids extracted from Radix aconiti preparata after oral administration to rats.
    Yao xue xue bao = Acta pharmaceutica Sinica, 2005, Volume: 40, Issue:6

    To develop an HPLC method for the determination of Aconitum alkaloids extracted from Radix aconiti preparata in rats.. Waters 2690@996 PAD system was used. The analytical column was a Halsil 100 C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase was water, methanol and diethyl amine at the ratio of 75:25:0.1. The flow rate was 0.9 mL.min(-1). The wavelength of the detector was 240 nm.. The linear ranges of aconitine in the heart, spleen, lung and kidney were 0.4-100 microg.mL(-1), the correlation coefficients were 0.9972, 0.9986, 0.9993 and 0.9994, respectively. The linear range of aconitine in liver was 2-200 microg.mL(-1) and the correlation coefficient was 0.9990. The linear ranges of hypaconitine in heart, liver, spleen, lung, kidney, brain and spinal cord were 5-100 microg.mL(-1), the correlation coefficients were 0.9994, 0.9997, 0.9998, 0.9984, 0.9998, 0.9998 and 0.9997, respectively. Detection limits (S/N = 3) of aconitine and hypaconitine were 0.4 microg.mL(-1). The recoveries of aconitine and hypaconitine ranged from 88.7% to 102.2% and 86.5% to 101.3%, respectively, and the RSD of precision of aconitine and hypaconitine was 10%.. It appears to be an accurate and effective method that can offer reference basis for in toxication of Radix aconiti preparata clinically.

    Topics: Aconitine; Aconitum; Administration, Oral; Animals; Drugs, Chinese Herbal; Kidney; Liver; Male; Myocardium; Plant Roots; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Spleen; Tissue Distribution

2005
Alkaloidal constituents from Aconitum jaluense.
    Archives of pharmacal research, 2003, Volume: 26, Issue:9

    Aconitum jaluense Komar. (Ranunculaceae) is one of the Aconitum plants growing in Korean peninsula. An investigation of the alkaloidal constituents of this species led to the isolation of seven C19-norditerpenoid and a C20-diterpenoid alkaloid. Three of them have been identified as neoline, mesaconitine, and hypaconitine, which were isolated from this plant collected from Mt. Bultasan in the north part. The other five alkaloids were determined as lipomesaconitine, lipohypaconitine, 15alpha-hydroxyneoline, hokbusine A, and napelline, which have not been found in this plant. Structures of those alkaloids were determined on the basis of their spectral data. It is of interest to note that a comparison of the present work and the previous report showed some differences in the alkaloidal contents.

    Topics: Aconitine; Aconitum; Alkaloids; Diterpenes; Korea; Plant Extracts; Plant Roots; Spectrophotometry, Infrared

2003
[Determination of aconitine alkaloids in a pesticide--0.25% aconitine alkaloids mixed with emulsion by high performance liquid chromatography].
    Se pu = Chinese journal of chromatography, 2002, Volume: 20, Issue:3

    The raw root of Aconitum, an important Chinese traditional medicine, contains some very toxic alkaloids such as aconitine, mesaconitine and hypaconitine etc. They are usually processed to lower the alkaloid content before used as a drug. The extract of crude drug (aconite) can be made into a plant pesticide by means of mixing with some emulsion. In order to evaluate the quality of the pesticide, we developed a rapid, specific and precise method using high performance liquid chromatography (HPLC) for the separation and quantitation of the alkaloids in the aconite extract and the mixed products (the aconite extract is mixed with emulsion). Before the determination by HPLC, the sample must be acidified with 2% (mass percentage) HCl at first. Extract the acid liquid with CHCl3. Alkalize the extract with ammonia, and add a little of 0.1 mol/L NaHCO3 and 0.1 mol/L Na2CO3 till pH 9. Extract it with CHCl3. Evaporate the extract and add a certain amount of methanol. Add the internal standard into the sample. Inject the combined sample solution onto a column of chemically bonded octadecylsilane phase and develop the chromatogram with MeOH-H2O-CHCl3-triethylamine (68:32:2:0.1, volume ratio). Aconitine, mesaconitine, hypaconitine and medroxyprogesteroni acetas (internal standard) were on base line separated. Quantify the alkaloids by peak area ratio (aconitine alkaloids vs internal standard). This method has high recovery (> 92%) and good reproducibility (RSD < 3.2%).

    Topics: Aconitine; Aconitum; Chromatography, High Pressure Liquid; Emulsions; Insecticides; Reproducibility of Results

2002
[The method for determination of aconitum alkaloids in Radix Aconiti Kusnezoffii].
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials, 2002, Volume: 25, Issue:12

    The methods for the determination of Aconitum alkaloids in Radix Aconiti Kusnezoffii were established. Volumetric analysis with the indicator of methyl red-bromcresol green and colorimetric analysis with acid dye of bromecresol green under the wavelength of 416 nm were used for the assay of total alkaloids. Colorimetric analysis of hydroxamic acid-Fe was for the assay of total ester-diterpene type Aconitum alkaloids. Three kinds of diester-diterpene type Aconitum alkaloids (aconitine, hypaconitine and mesaconitine) were determined by HPLC method. The HPLC system consisted of C18 as the stationary phase and acetonitrile: buffer (acetic acid-triethylamine, pH 6.25) = 71:29 as the mobile phase. The wavelength was 235 nm.

    Topics: Aconitine; Aconitum; Alkaloids; Chromatography, High Pressure Liquid; Colorimetry; Coloring Agents; Drugs, Chinese Herbal; Pharmacognosy

2002
[Determination of the aconitine alkaloids in traditional Chinese medicine chuanwu and caowu by high performance capillary electrophoresis(HPCE)].
    Se pu = Chinese journal of chromatography, 1999, Volume: 17, Issue:1

    A simple and rapid method for the simultaneous assay of three aconitine alkaloids (mesaconitine (MA), hypaconitine (HA) and aconitine (A) in the traditional Chinese medicines, Chuanwu and Caowu, by high performance capillary electrophoresis has been established, using tetracaine as an internal standard. The experimental conditions were as follows, the electrophoretic medium was composed of V[70 mmol/L Tris-borate (pH 8.49)]: V(methanol) = 60:40, uncoated capillary used was 50 cm x 50 microns i.d. and detection was carried out with a UV monitor at 235 nm. The separation was achieved by optimizing the cartridge temperature, the applied voltage, and the pH as well as the concentration of the buffer, and organic modifier. The calibration curve showed a good linearity in the mass concentration range of 0.0115-0.8330 g/L (r = 0.9996) for MA, 0.0089-0.6440 g/L (r = 0.9997) for HA, and 0.0083-0.6000 g/L(r = 0.9997) for A. The recoveries ranged from 93.0% to 104.0% with relative standard deviations from 0.68% to 1.7%. The total time for separation and determination was within 23 min. By means of this method, three aconitine alkaloids in Chuanwu and Caowu have been determined.

    Topics: Aconitine; Aconitum; Electrophoresis, Capillary; Ranunculaceae

1999
Determination of Aconitum alkaloids in blood and urine samples. I. High-performance liquid chromatographic separation, solid-phase extraction and mass spectrometric confirmation.
    Journal of chromatography. B, Biomedical sciences and applications, 1997, Apr-11, Volume: 691, Issue:2

    Determination of four toxic Aconitum alkaloids, aconitine, mesaconitine, hypaconitine and jesaconitine, in blood and urine samples has been established using high-performance liquid chromatography (HPLC) combined with ultraviolet absorbance detection, solid-phase extraction and mass spectrometry (MS). These alkaloids were hydrolyzed rapidly in alkaline solution (half lives (t1/2)five months) and were unstable in solutions of methanol and ethanol (t1/2

    Topics: Aconitine; Alkaloids; Chromatography, High Pressure Liquid; Drug Stability; Humans; Plants, Medicinal; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Ultraviolet

1997
[Optimization of technical parameters for processing radix Aconiti coreani].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 1997, Volume: 22, Issue:10

    Based on the determination of guanfu A, hypaconitine, and total alkaloids, along with the experiment of acute toxicity of sliced Radix Aconiti Coreani and in compliance with the quality standard stipulated in pharmacopeia-surface features cross section colour and odor of sliced Radix Aconiti Co-reani the technology of processing Radix Aconiti Coreani has been optimized to be steaming the drug for four hours.

    Topics: Aconitine; Alkaloids; Drugs, Chinese Herbal; Heterocyclic Compounds, 4 or More Rings; Hot Temperature; Magnoliopsida; Plants, Medicinal; Quality Control; Technology, Pharmaceutical

1997
[Influence of processing on the content of hypaconitine in the roots of Aconitnum coreanum (Lévl.) Rapaics].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 1997, Volume: 22, Issue:5

    In this paper, the contents of hypaconitine in the roots of Aconitum coreanum and its processed products were determined by high performance liquid chromatography. The result provides scientific basis for processing the roots of Aconitum coreanum.

    Topics: Aconitine; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hot Temperature; Magnoliopsida; Pharmacognosy; Plants, Medicinal; Technology, Pharmaceutical

1997
A case of aconitine poisoning with analysis of aconitine alkaloids by GC/SIM.
    Forensic science international, 1996, Aug-15, Volume: 81, Issue:2-3

    Described here is a fatal case of accidental aconitine poisoning following the ingestion of aconite, Torikabuto, mistaken for an edible grass, Momijigasa. A 61-year-old man developed symptoms of nausea, diarrhea, and discomfort of the body about 2 h after the ingestion and was taken to an emergency room. Resuscitation and antiarrhythmic drugs were ineffective, and ventricular tachycardia and fibrillation developed and lasted for 6 h. He was transferred to a coronary care unit and complete sinus rhythm was obtained on an electrocardiogram 30 h after his admission. The patient fell into a coma and died of brain edema diagnosed by CT on the 6th day. Consent for autopsy was denied by the family but was given for gas chromatography/selected ion monitoring (GC/SIM) to analyze the toxicity of aconitine alkaloids in the blood and the urine. Only a faint amount of jesaconitine was detected, while aconitine, mesaconitine and hypaconitine were not detectable in the blood 24 h after ingestion. On the other hand, aconitine and its related alkaloids such as mesaconitine, jesaconitine, and hypaconitine were clearly detected in the urine.

    Topics: Aconitine; Chromatography, Gas; Fatal Outcome; Forensic Medicine; Humans; Ion-Selective Electrodes; Male; Middle Aged; Plants, Edible; Poaceae; Poisoning

1996
[Construction and application of all-solid-state aconitine electrochemical detector in flow injection analysis].
    Yao xue xue bao = Acta pharmaceutica Sinica, 1992, Volume: 27, Issue:4

    A new kind of all-solid-state electrochemical detector for very toxic alkaloids such as aconitine, mesaconitine and hypaconitine has been studied. It exhibits Nernstian response for these alkaloids with a slope of 56 mV/decade over the concentration range of 3 x 10(-5)-1 x 10(-2) mol/L at pH 2-7 under the flow condition. Direct potentiometry for the determination of aconitine in Aconitum kusnezoffii Reichb., Aconitum carmichaeli Debx. and Xiaohuoluo Wan showed average recoveries of 98.5, 98.3 and 96.8% and relative standard deviations of 1.8, 2.4 and 3.5%, respectively. It can be used for the determination of very toxic alkaloids in the above mentioned samples by flow injection analysis. It also can be used for the study of the hydrolytic kinetics of aconitine.

    Topics: Aconitine; Drugs, Chinese Herbal; Electrochemistry; Flow Injection Analysis; Neuromuscular Blocking Agents

1992
[Determination of the main alkaloids in wu tou (aconite) by TLC-densitometry].
    Yao xue xue bao = Acta pharmaceutica Sinica, 1990, Volume: 25, Issue:5

    A method of TLC densitometry was established in order to determine the main alkaloids: mesaconitine, aconitine and hypaconitine in Aconite root. The powdered sample was alkalinized by ammonia and macerated with ether for 24 h. The mixture was then centrifuged, the residue was washed three times each with 2 ml of fresh ether, the combined ether extract was evaporated to dryness and then dissolved in 1 ml of dichloromethane. Standard solution and sample solution were spotted on a sillca gel GF254 plate, and developed with cyclohexane-ethyl acetate-diethylamine (8:1:1), the chromatogram was observed under UV light as dark spots. A Shimazu TLC model 910 was used for scanning at lambda s 236 nm and lambda R 350 nm by reflection mode. Linear calibration curves were obtained for the 3 constituents in the range of 2-6 micrograms. The average recoveries of masaconitine, aconitine and hypaconitine were 97.3, 96.4, 99.1% and the variation coefficients were 1.81, 1.72, 1.18%, respectively. The spots were stable for more than 24 h. Samples from various sources were analyzed.

    Topics: Aconitine; Aconitum; Chromatography, Thin Layer; Densitometry; Drugs, Chinese Herbal; Neuromuscular Blocking Agents

1990
Blocking effects of hypaconitine and aconitine on nerve action potentials in phrenic nerve-diaphragm muscles of mice.
    Neuropharmacology, 1990, Volume: 29, Issue:6

    The mechanisms of neuromuscular blockade by hypaconitine and aconitine were investigated electrophysiologically in isolated phrenic nerve-diaphragm muscles of mice. Hypaconitine (0.08-2 microM) and aconitine (0.3-2 microM) depressed the nerve-evoked twitch tension, without affecting the contraction evoked by stimulation of the muscle. At the concentrations of hypaconitine (up to 5 microM) and aconitine (up to 2 microM) that depressed the nerve-evoked twitch tension, the resting membrane potential of the muscle cells was unchanged. Hypaconitine (0.1-2 microM) and aconitine (2 microM) blocked the end-plate potential (epp), without affecting the amplitude of the miniature epp (mepp). The quantal content of end-plate potentials was decreased by these agents in parallel with the decrement in amplitude. The nerve compound action potential was inhibited by hypaconitine (5 microM) and aconitine (2-10 microM), as well as by 1 microM tetrodotoxin (TTX). When the nerve compound action potential was completely blocked by 2 microM aconitine, the muscle action potential was unaffected, although 1 microM TTX suppressed both potentials to the same degree. These results indicate the neuromuscular blockade produced by hypaconitine and aconitine were caused by reducing the evoked quantal release. The mechanism of this effect was attributed mainly to blocking of the nerve compound action potential.

    Topics: Aconitine; Aconitum; Action Potentials; Animals; Male; Membrane Potentials; Mice; Mice, Inbred Strains; Microelectrodes; Motor Endplate; Muscle Contraction; Neuromuscular Blocking Agents; Neurons; Phrenic Nerve; Respiratory Muscles; Synapses

1990
[Determination of alkaloids in Aconite roots by HPLC].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 1990, Volume: 15, Issue:2

    Three alkaloids contained in Aconite roots, aconitine, mesaconitine and hypaconitine, were determined by HPLC. 15 samples (8 species) of Aconite roots were analysed. The results reveal that most of them contain the three alkaloids in different contents, and some of them contain one or two alkaloids.

    Topics: Aconitine; Aconitum; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal

1990
Hypaconitine, the dominant constituent responsible for the neuromuscular blocking action of the Japanese-sino medicine "bushi" (aconite root).
    Japanese journal of pharmacology, 1988, Volume: 48, Issue:2

    The neuromuscular blocking actions of several constituents extracted from Japanese-sino medicine, aconite, were compared in mouse phrenic nerve-diaphragm muscle preparations. Hypaconitine (HAT) was more potent than aconitine (ATN), mesaconitine (MAT) and deoxyaconitine. Lipohypaconitine, coryneine and lipodeoxyaconitine were less effective. Lipoaconitine, benzoylmesaconine, higenamine, kobusine and chasmanine were not effective. The blockades by HAT, ATN and MAT were not recovered by neostigmine. The mechanisms of blockade were similar to that of aconite crude extract. These results suggest that aconite action is dependent on HAT, a main constituent.

    Topics: Aconitine; Aconitum; Animals; In Vitro Techniques; Japan; Male; Mice; Neuromuscular Blocking Agents; Neuromuscular Junction; Phytotherapy; Plants, Medicinal

1988