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1.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3695-3704, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602941

RESUMO

Aconitums,represented by Aconite Radix,Aconiti Lateralis Radix Praeparata and Aconiti Kusnezoffh Folium,is a kind of traditional Chinese medicine with a long medicinal history in China. They possess the significant toxicity and therapeutic effects simultaneously. Their potent effects of rescuing from dying,curing rheumatism,anti-inflammation,and analgesia make Aconitums highly regarded by physicians and pharmacists of various dynasties. However,countless poisoning cases caused by an irrational use of Aconitums were reported. In case of improper application and exceeding the therapeutic window,the acute cardiotoxicity and neurotoxicity would be caused,seriously threatening health and even life of the users. Therefore,the clinical application of Aconitums is limited to some extent. To avoid its toxicity and ensure the safety of medicinal use,Aconitums is usually used in a form of its processed products instead of the crude herbs,or combined with some other traditional Chinese medicines in a normal prescription. A proper processing and compatibility method can detoxicate its severe toxicity,reduce the adverse reactions,and also significantly broaden the indications and application range of Aconitums. This provides a guarantee for the secondary exploitation and utilization of Aconitums. In this paper,the traditional processing methods of Aconitums,along with the modern advancement were reviewed,and the mechanisms of detoxification by processing and compatibility were also illuminated. The physical detoxification mode and chemical detoxification mode were found as two main detoxification ways for Aconitums. In particular,the detoxification by hydrolysis,ion-pair,and saponification were three main means. The mechanisms illustrated in this paper can be a reference to the development of modern processing method and a guidance for appropriate use of Aconitums in clinical application.


Assuntos
Aconitum/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Aconitum/toxicidade , China , Medicamentos de Ervas Chinesas/toxicidade , Medicina Tradicional Chinesa , Folhas de Planta/química , Raízes de Plantas/química
2.
Zhongguo Zhong Yao Za Zhi ; 44(5): 1010-1018, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989863

RESUMO

The aim of this paper was to provide reference for the clinical safety use of aconite through the retrieval of literature about adverse reactions,predict its mechanism of cardiac toxicity by using network pharmacology,and provide ideas for the studies on toxicity mechanism of toxic Chinese medicines. The papers on adverse reactions of aconite were searched to established a database and summarize the adverse reactions of aconite. The results of literature review showed that the main causes for adverse reactions in clinical use of aconite included overdose use,short cooking time,consumption of medicinal liquor/medicinal diet,external use and misuse and so on. Therefore,the dosage of aconite should be strictly followed in clinical application,and the decoction method should be notified to the patients in detail to avoid taking the medicinal liquor and diet containing aconite,so as to prevent the occurrence of adverse reactions as much as possible,and make the best use of aconite in clinical application in avoid its toxicity. At the same time,based on the results of literature review,the network construction and visual analysis of cardio toxicity produced by aconite were carried out by using the network pharmacology technologies. RESULTS: showed that aconite can be applied to eight biological processes such as action potential of cardiac myocytes,cardiac conduction-related cell signal transduction,cardiac myocytes contraction,action potential involved in cardiac myocytes contraction,and signal transduction from atrial myocardial cells to atrioventricular node cells,and three target genes(SCN5 A,GJA1,GJA5). It was predicted that Aconiti Lateralis Radix Praeparata may influence cardiomyocyte depolarization,intercellular information transmission and material exchange by acting on three target genes(SCN5 A,GJA1,GJA5) and regulating the sodium channel protein and the expression of gap junction protein,thus affecting the heart rhythm as well as its structure and function and causing cardiac toxicity.


Assuntos
Aconitum/química , Cardiotoxicidade , Medicamentos de Ervas Chinesas/toxicidade , Aconitum/toxicidade , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Raízes de Plantas/química , Raízes de Plantas/toxicidade
3.
Mol Med Rep ; 18(5): 4468-4476, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30221717

RESUMO

Aconitum plants, which have analgesic, diuretic and anti­inflammatory effects, have been widely used to treat various types of disease. However, the apparent toxicity of Aconitum­derived agents, particularly in the cardiovascular system, has largely limited their clinical use. Thus, the present study investigated whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were randomly divided into four groups: Control, Chuan­wu and Chuan­wu + Ber (8 and 16 mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK) and CK­MB] were assayed. Histopathological changes were assessed using myocardial tissue sectioning and hematoxylin and eosin staining. Additionally, the effects of Ber on AC­induced arrhythmias in rats were observed. The changes in ECG following AC perfusion were observed, and the types and onset time of arrhythmias were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action potentials were observed. The results suggested that Ber ameliorated myocardial injury induced by Chuan­wu, which was indicated by reduced arrhythmias and decreased LDH, CK and CK­MB levels in serum. Furthermore, histological damage, including dilation of small veins and congestion, was also markedly attenuated by Ber. In addition, the occurrence of arrhythmias was significantly delayed, and the dosage of AC required to induce arrhythmias was also increased by Ber pretreatment. Additionally, AC­induced changes in action potential amplitude, duration of 30% repolarization and duration of 90% repolarization in the papillary muscle were attenuated by Ber. All of these results indicate that Ber had a preventive effect on acute myocardial injury induced by Chuan­wu and arrhythmias caused by AC, which may be associated with the inhibition of delayed depolarization and triggered activity caused by AC. Thus, combination treatment of Ber with Aconitum plants may be a novel strategy to prevent AC­induced myocardial injury in clinical practice.


Assuntos
Aconitum/toxicidade , Berberina/administração & dosagem , Traumatismos Cardíacos/tratamento farmacológico , Miocárdio/patologia , Aconitum/química , Animais , Creatina Quinase Forma MB/sangue , Eletrocardiografia , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/fisiopatologia , Humanos , L-Lactato Desidrogenase/sangue , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos
4.
Zhongguo Zhong Yao Za Zhi ; 43(15): 3093-3100, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30200703

RESUMO

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.


Assuntos
Aconitum/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Raízes de Plantas/toxicidade , Aconitina/toxicidade , Alcaloides/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Humanos
5.
Zhongguo Zhong Yao Za Zhi ; 43(2): 205-210, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29552833

RESUMO

Based on the relation of efficacy and toxicity, this study mined the dosage rules and characteristics of Aconitum herbs in oral prescriptions from 48 traditional ancient books from Eastern Han dynasty to Qing dynasty, to provide the basis for strengthening the clinical risk pharmacovigilance. In the 48 traditional ancient books, 4 521 prescriptions with clear daily oral dosage were included to establish a database. SPSS 20.0 software was used for statistics and analysis of the daily dosage characteristics with different kinds of herbs, indications, dose forms, processing, use in special population, and other aspects. The results showed that 67% prescriptions contained Aconitum carmichaeli(Fuzi), and 90% of them was less than 14.87 g·d⁻¹; The dosage of A. carmichaeli(Chuanwu) and A. kusnezoffii(Caowu) were less than 3.14 g·d⁻¹. In the prescriptions for treating typhoid, epidemic, edema and phlegm, the dosage of Aconitum was larger. There dosage in the decoction and vinum was significantly higher than that in the pill and powder. With the dynastic evolution, the dosage of Aconitum herbal medicines prescriptions and the application percentage of superposition drug also had decreased. For the special populations that with different metabolism process, such as old people, children, pregnant and lactating women, the application of Aconitum was not only with relatively small ratio, but also with lower dose. Therefore, based on the data-mining of ancient books, the dosage of Aconitum should not exceed the limit prescribed by the current China Pharmacopoeia, and also should be strictly controlled by considering various factors, which will ensure the balance of efficacy and toxicity.


Assuntos
Aconitum/química , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Aconitum/toxicidade , China , Mineração de Dados , Medicamentos de Ervas Chinesas/toxicidade , Humanos
6.
Planta Med ; 84(6-07): 434-441, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29076119

RESUMO

Despite their well-known toxicity, Aconitum species are important traditional medicines worldwide. Aconitum carmichaelii, known in Chinese as (fuzi), is an officially recognized traditional Chinese medicine with characteristic analgesic and anti-inflammatory activities, whose principal pharmacological ingredients are considered as aconitine-type diterpene alkaloids. Notwithstanding the long-recorded use of A. carmichaelii in traditional Chinese medicine, no single-entity aconitum alkaloid drug has been developed for clinical use. UPLC-Q-TOF-MS was used to investigate the marker compounds that can be used to differentiate A. carmichaelii from seven other Aconitum species collected in Yunnan Province. Nontargeted principle component analysis scores plots found that all the tested Aconitum species clustered into three distinct groups, and A. carmichaelii was significantly different chemically than the other seven species. Furthermore, the primary and lateral roots of A. carmichaelii also showed significant differences. Using orthogonal partial least squares discriminate analysis analysis, eight marker compounds were identified, including 14-acetylkarakoline, aconitine, carmichaeline, fuziline, hypaconitine, mesaconitine, neoline, and talatisamine. Four of these aconitum alkaloids, fuziline, hypaconitine, mesaconitine, and neoline, showed significant analgesic activity in a dose-dependent manner compared to the negative and positive controls. However, hypaconitine, mesaconitine, and neoline exhibited significant acute toxicity activity, while fuziline showed no acute toxicity in mice, suggesting the relative safety of this alkaloid. This study provides a good example of how to differentiate an authentic medicinal plant from common adulterants using a metabolomics approach, and to identify compounds that may be developed into new drugs.


Assuntos
Aconitum/química , Medicina Tradicional Chinesa/métodos , Aconitum/toxicidade , Analgésicos/farmacologia , Animais , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão/métodos , Relação Dose-Resposta a Droga , Feminino , Masculino , Metabolômica/métodos , Camundongos , Espectrometria de Massas em Tandem/métodos
7.
J Ethnopharmacol ; 207: 237-250, 2017 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-28666834

RESUMO

CONTEXT: Aconitum species are well-known for their medicinal value and high lethal toxicity in many Asian countries, notably China, India and Japan. The tubers are only used after processing in Traditional Chinese Medicine (TCM). They can be used safely and effectively with the methods of decoction, rational compatibility, and correct processing based on traditional experiences and new technologies. However, high toxicological risks still remain due to improper preparation and usage in China and other countries. Therefore, there is a need to clarify the methods of processing and compatibility to ensure their effectiveness and minimize the potential risks. OBJECT: The aim of this paper is to provide a review of traditional and current methods used to potentially reduce toxicity of Aconitum roots in TCM. MATERIALS AND METHODS: The use of Aconitum has been investigated and the methods of processing and compatibility throughout history, including recent research, have been reviewed. RESULTS AND CONCLUSIONS: Using of the methods of rational preparation, reasonable compatibility, and proper processing based on traditional experiences and new technologies, can enable Aconitum to be used safely and effectively.


Assuntos
Aconitum/química , Medicamentos de Ervas Chinesas/toxicidade , Preparações de Plantas/toxicidade , Aconitum/toxicidade , Animais , Química Farmacêutica/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Medicina Tradicional Chinesa/métodos , Preparações de Plantas/administração & dosagem , Raízes de Plantas , Tecnologia Farmacêutica/métodos
8.
J Ethnopharmacol ; 205: 138-146, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28456577

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. AIM OF THE STUDY: The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite. MATERIALS AND METHODS: For acute protection Study, single dose of toxicant (35mg/kg) and test drug (22.5mg/kg and 112.5mg/kg) was administered orally, and then 24h survival of animals was observed. The schedule was continued for 30 days in sub-acute protection Study with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg and 112.5mg/kg) and vehicle. Hematological and biochemical tests of blood and serum, histopathology of vital organs were carried out. The cardiac activity Study was continued for 30 days with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg), processed borax solution (22.5mg/kg) and vehicle; ECG was taken after 1h of drug administration on 1TB, 15th and on 30th day. For neuro-muscular activity Study, the leech dorsal muscle response to 2.5µg of acetylcholine followed by response of toxicant at 25µg and 50µg doses and then response of test drug at 25µg dose were recorded. RESULTS: Protection index indicates that treated borax gave protection to 50% rats exposed to the lethal dose of toxicant in acute protection Study. Most of the changes in hematological, biochemical parameters and histopathological Study induced by the toxicant in sub-acute protection Study were reversed significantly by the test drug treatment. The ventricular premature beat and ventricular tachyarrhythmia caused by the toxicant were reversed by the test drug indicate reversal of toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech muscle were inhibited by toxicant and it was reversed by test drug treatment. CONCLUSION: The processed borax solution is found as an effective protective agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and neuro-muscular toxicity. Processed borax at therapeutic dose (22.5mg/kg) has shown better antidotal activity profile than five times more than therapeutic dose (112.5mg/kg).


Assuntos
Aconitum/toxicidade , Antídotos/uso terapêutico , Boratos/uso terapêutico , Intoxicação por Plantas/tratamento farmacológico , Acetilcolina/farmacologia , Animais , Feminino , Masculino , Distribuição Aleatória , Ratos
9.
Chin J Nat Med ; 15(1): 49-61, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28259253

RESUMO

Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.


Assuntos
Aconitum/química , Alcaloides/análise , Medicamentos de Ervas Chinesas/química , Aconitum/efeitos adversos , Aconitum/toxicidade , Alcaloides/efeitos adversos , Alcaloides/toxicidade , Animais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/normas , Fármacos Cardiovasculares/toxicidade , Dessecação/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/normas , Medicamentos de Ervas Chinesas/toxicidade , Masculino , Dose Máxima Tolerável , Raízes de Plantas/química , Ratos Sprague-Dawley , Tecnologia Farmacêutica/métodos
10.
Phytomedicine ; 23(13): 1591-1598, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27823623

RESUMO

BACKGROUND: Aconitum brachypodum Diels (Family Ranunculaceae) is a Chinese ethnodrug and is well known for both its therapeutic application and high toxicity. However, no detoxication strategy is available for the complete elimination of the toxicity of Aconitum plants. Veratrilla baillonii Franch is believed to possess antitoxic effects on the toxicity induced by Aconitum plants and has been clinically used for hundreds of time by Naxi and Lisu nationalities in Yunnan Province of China. To further address the mechanism of the detoxication of Veratrilla baillonii, the effect of water decoction of Veratrilla baillonii (WVBF) on subacute toxicology of SD rats induced by Aconitum brachypodum (CFA), a genus Aconitum, was determined and studied in the present work. METHODS: The clinical behavior and number of survivors for different dosage of WVBF (25, 50, 100mg/kg) on CFA (4mg/kg) induced rats were observed until day 28. Histological changes and haematological parameters were evaluated. Moreover, Na+-K+-ATPase pathway in heart as well as key enzymes in liver were determined to further discuss the mechanism. RESULTS: The results showed that the exposure of CFA led to some subacute toxicity to rats, especially male ones, accompanied with abnormality of serum biochemical index in rats' serum. The toxicological target organs of CFA may be the heart, liver, kidney and brain. It is demonstrated that WVBF could attenuate the toxicity induced by Aconitum brachypodum via promoting the metabolic enzymes CYP3A1 and CYP3A2 in liver, downregulating the expression of Sodium/Calcium exchanger 1 (NCX1) and SCN5A sodium channal mRNA, and inducing Na+/K+-ATPase activity in heart. This study provides insights into detoxifying measures of Aconitum plants. CONCLUSIONS: Aconitum brachypodum may lead to subacute toxicity of rats after long term of administration, and the toxicity could be attenuated by Veratrilla baillonii via promoting the metabolic enzymes in liver, downregulating the expression of NCX1 and SCN5A mRNA, and inducing Na+/K+-ATPase activity in heart.


Assuntos
Aconitum/toxicidade , Gentianaceae/química , Extratos Vegetais/farmacologia , Animais , China , Citocromo P-450 CYP3A/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Coração/efeitos dos fármacos , Inativação Metabólica/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Medicina Tradicional Chinesa , Ratos Sprague-Dawley , Trocador de Sódio e Cálcio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
11.
Zhongguo Zhong Yao Za Zhi ; 41(20): 3814-3820, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-28929660

RESUMO

Aconiti Lateralis Radix (Fuzi) is a toxic traditional Chinese medicine with definite efficacy. In order to improve the quality control of its different prepared products and ensure the security in clinic, it is significant to establish a method of quality evaluation related to clinic adverse effects. Aiming at the important biological marker of early cardiac toxicity reaction, there was no method to detect it. In this manuscript, a novel approach for measuring the minimal toxic dose (MTD) of premature ventricular contractions (PVC) poisoning of rats was established. Then, the determination methodology and conditions were optimized to meet the needs of the quality and biological assessment, including animal sex, weight, stability of standards and test solutions. Using this method, the MTD value of different Fuzi products were determined, such as Heishunpian, Baifupian, Zhengfupian, Baofupian, and Paotianxiong. The results showed that the MTD of Fuzi was significantly decreased after detoxification processed (P<0.05) and the MTD of Heishunpian, Zhengfupian, Baofupian and Baifupian was as much as 15.76, 22.36, 19.65 and 20.97 times to that of unprocessed Shengfuzi. In addition, Paotianxiong could not induce PVC in rats, which indicated that Paotianxiong was nontoxic and safe.This method could appropriately reflects the cardiotoxity of Fuzi and its prepared samples. Together with the chemical composition analysis, the contents of diester alkaloids were explored including aconitine, mesaconitine and hypaconitine as well as monoester alkaloids in Fuzi and its prepared products were significantly associated with PVC. Furthermore, there may be some components undetermined facilitating arrhythmia to be worth exploring. This research provides an overall and comprehensive approach to diagnose early clinical cardiotoxity and control the quality of Fuzi, which could not only be a complementary solution for the chemical evaluation, but a new method to ensure its efficacy and security of clinical application.


Assuntos
Extratos Vegetais/normas , Complexos Ventriculares Prematuros/induzido quimicamente , Aconitina/análise , Aconitum/toxicidade , Alcaloides/análise , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Extratos Vegetais/toxicidade , Controle de Qualidade , Ratos , Testes de Toxicidade
12.
Chin J Nat Med ; 13(9): 687-98, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26412429

RESUMO

Chuanwu (CW), a famous traditional Chinese medicine (TCM) from the mother roots of Aconitum carmichaelii Debx.. (Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao (Radix Glyeyrrhizae, CG), Baishao (Radix Paeoniae Alba, CS) and Ganjiang (Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.


Assuntos
Aconitum/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Medicamentos de Ervas Chinesas , Gengibre , Glycyrrhiza uralensis , Metaboloma , Paeonia , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/toxicidade , Coração , Inativação Metabólica , Fígado , Masculino , Espectrometria de Massas/métodos , Medicina Tradicional Chinesa , Metabolômica , Raízes de Plantas , Ratos Wistar , Rizoma
13.
Zhongguo Zhong Yao Za Zhi ; 40(4): 661-6, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26137687

RESUMO

The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 ± 2.02) nm and (238.20 ± 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.


Assuntos
Aconitum/química , Medicamentos de Ervas Chinesas/toxicidade , Glycyrrhiza/química , Proteínas de Plantas/química , Aconitum/toxicidade , Animais , Feminino , Glycyrrhiza/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/toxicidade , Rizoma/química , Rizoma/toxicidade
14.
Zhongguo Zhong Yao Za Zhi ; 40(4): 733-8, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26137699

RESUMO

OBJECTIVE: To explore the intersection and regulation mechanism of "efficacy-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata's action gene in the combination environment of Sini decoction with the network pharmacological method. METHOD: The gene interaction network of Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma were mined and established with Cytoscape software and Agilent literature search plug-in. The "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata was formed according to its effects in anti-heart failure, neurotoxicity and cardiotoxicity. The target genes were clustered with Clusterviz plug-in. And the possible pathways of the "efficacy-tox- icity network" intersection of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata were forecasted in DAVID database. RESULT: There were five genes related to neurotoxicity, cardiotoxicity and anti-heart failure function of Aconiti Lateralis Radix Praeparata, namely AKT1, BAX, HCC, IL6 and IL8, which formed 47 nodes genes in the "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata. There were 29 and 27 coincident genes in the "efficiency-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata. There were 23 and 17 possible regulatory pathways. CONCLUSION: In the combination environment of Sini decoction, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma may regulate the efficiency-toxicity network of Aconiti Lateralis Radix Praeparata by influencing immune-inflammatory signaling pathway, apoptosis-autophagy signaling pathway, nerve cell and myocardial ischemia and hypoxia protection signaling pathways.


Assuntos
Aconitum/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Redes Reguladoras de Genes/efeitos dos fármacos , Aconitum/química , Medicamentos de Ervas Chinesas/química , Humanos , Rizoma/química , Rizoma/toxicidade
15.
Toxins (Basel) ; 7(1): 138-55, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25594733

RESUMO

Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms of their significance in traditional Tibetan medicinal practices. They are Aconitum pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for which the toxic chemical constituents, bioactivities and pharmacological functions are reviewed herein. The most important toxins include aconitine, strychnine, scopolamine, and anisodamine. These toxic plants are still currently in use for pain-reduction and other purposes by Tibetan healers after processing.


Assuntos
Plantas Tóxicas , Aconitum/química , Aconitum/toxicidade , Animais , Humanos , Medicina Tradicional , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Plantas Tóxicas/química , Plantas Tóxicas/toxicidade , Solanaceae/química , Solanaceae/toxicidade , Strychnos/química , Strychnos/toxicidade , Tibet
16.
Zhongguo Zhong Yao Za Zhi ; 39(11): 1972-5, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25272824

RESUMO

Aconitum, as a kind of common traditional Chinese medicine, contains multiple biological active substances, with a very high medicinal value but high toxicity. Its major toxic ingredients are aconitine, mesaconitine and hypaconitine, which are also efficient ingredients. Therefore, the safety of its clinical application has aroused wide attention. With the constant deepening of drug development studies, people want to learn about its toxic mechanism and the regularity of its emergence and development of its toxicology, so as to make a scientific and rational assessment for its safety. Therefore, toxicokinetics and metabonomics have gradually become important content in the new drug assessment. During the development of drug performance, it is crucial to establish a scientific, objective and standardized Aconitum safety evaluation system and correctly assess and utilize its toxicity. Having summarized studies on metabonomics and toxicokinetics of Aconitum drugs in recent years, authors proposed to strengthen the studies on Aconitum drug safety assessment and establish a scientific and standardized safety evaluation system as soon as possible, in order to make the national treasure more useful.


Assuntos
Aconitum/toxicidade , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/toxicidade , Aconitum/química , Animais , Humanos , Metabolômica
17.
J Hazard Mater ; 199-200: 350-7, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22118852

RESUMO

Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs.


Assuntos
Aconitum/toxicidade , Animais , Bioensaio , Columbidae , Feminino , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos ICR , Controle de Qualidade , Ratos , Ratos Endogâmicos F344 , Ratos Wistar
18.
J Proteome Res ; 11(2): 1284-301, 2012 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-22053844

RESUMO

The mother and lateral root of Aconitum carmichaelii Debx, named "Chuanwu" (CW) and "Fuzi", respectively, has been used to relieve joint pain and treat rheumatic diseases for over 2000 years. However, it has a very narrow therapeutic range, and the toxicological risk of its usage remains very high. The traditional Chinese processing approach, Paozhi (detoxifying measure),can decompose poisonous Aconitum alkaloids into less or nontoxic derivatives and plays an important role in detoxification. The difference in metabolomic characters among the crude and processed preparations is still unclear, limited by the lack of sensitive and reliable biomarkers. Therefore, this paper was designed to investigate comprehensive metabolomic characters of the crude and its processed products by UPLC-Q-TOF-HDMS combined with pattern recognition methods and ingenuity pathway analysis (IPA). The significant difference in metabolic profiles and changes of metabolite biomarkers of interest between the crude and processed preparations were well observed. The underlying regulations of Paozhi-perturbed metabolic pathways are discussed according to the identified metabolites, and four metabolic pathways are identified using IPA. The present study demonstrates that metabolomic analysis could greatly facilitate and provide useful information to further comprehensively understand the pharmacological activity and potential toxicity of processed Aconite roots in the clinic.


Assuntos
Aconitum/toxicidade , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/toxicidade , Metaboloma/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Biomarcadores/metabolismo , Histocitoquímica , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica/métodos , Análise Multivariada , Miocárdio/química , Miocárdio/ultraestrutura , Reconhecimento Automatizado de Padrão/métodos , Raízes de Plantas/toxicidade , Análise de Componente Principal , Ratos , Ratos Wistar
19.
Pharm Biol ; 49(10): 1097-101, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21936629

RESUMO

CONTEXT: In traditional Chinese medicine, Aconitum (Ranunculaceae) roots are only applied after processing. Nevertheless, several cases of poisoning by improperly processed aconite roots have been reported. OBJECTIVE: The aim of this study was to develop a reliable analytical method to assess the amount of toxic aconite alkaloids in commercial aconite roots, and to compare this method with the commonly used total alkaloid content determination by titration. MATERIALS AND METHODS: The content of mesaconitine, aconitine, and hypaconitine in 16 commercial samples of processed aconite roots was determined by an HPLC method and the total alkaloid content by indirect titration. Five samples were selected for in vivo toxicological investigation. RESULTS: In most of the commercial samples, toxic alkaloids were not detectable, or only traces were found. In four samples, we could detect >0.04% toxic aconite alkaloids, the highest with a content of 0.16%. The results of HPLC analysis were compared with the results obtained by titration, and no correlation was found between the two methods. The in vivo results reassured the validity of the HPLC determination. DISCUSSION AND CONCLUSION: Samples with mesaconitine, aconitine, and hypaconitine content below the HPLC detection limit still contained up to 0.2% alkaloids determined by titration. Since titration of alkaloids gives no information selectively on the aconitine-type alkaloid content and toxicity of aconite roots this method is not appropriate for safety assessment. The HPLC method developed by us provides a quick and reliable assessment of toxicity and should be considered as a purity test in pharmacopoeia monographs.


Assuntos
Aconitina/química , Aconitum/química , Alcaloides/química , Cromatografia Líquida de Alta Pressão/métodos , Aconitina/análise , Aconitina/toxicidade , Aconitum/metabolismo , Aconitum/toxicidade , Alcaloides/análise , Alcaloides/toxicidade , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Masculino , Camundongos
20.
Int J Legal Med ; 125(2): 211-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20623131

RESUMO

Some plants have toxicities that are dangerous for humans. In the case of poisoning by toxic plants, a rapid and easy screening test is required for accurate medical treatment or forensic investigation. In this study, we designed specific primer pairs for identification of toxic plants, such as subgenus Aconitum, genus Ricinus, genus Illicium, and genus Scopolia, by internal transcribed spacer sequences of nuclear ribosomal DNA. Allied species of target plants, foods, and human DNA were not detected, but each primer pair provided a specific PCR product from the target plant using real-time PCR. This method can detect the subgenus Aconitum, genus Ricinus, and genus Scopolia with template DNA of 10 pg, respectively, and genus Illicium with 1 pg. Furthermore, each primer pair provided the exact PCR product from digested target plants in artificial gastric fluid. When a trace unknown plant sample in forensic investigation is collected from stomach contents, this PCR assay may be useful for screening toxic plants.


Assuntos
DNA de Plantas/análise , Plantas Tóxicas/genética , Reação em Cadeia da Polimerase/métodos , Aconitum/classificação , Aconitum/genética , Aconitum/toxicidade , Primers do DNA , DNA de Plantas/genética , DNA Espaçador Ribossômico/genética , Humanos , Illicium/classificação , Illicium/genética , Illicium/toxicidade , Plantas Tóxicas/classificação , Plantas Tóxicas/toxicidade , RNA Nuclear/análise , Ricinus/classificação , Ricinus/genética , Ricinus/toxicidade , Scopolia/classificação , Scopolia/genética , Scopolia/toxicidade
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