According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.
Aconitum ; chemistry ; Alkaloids ; administration & dosage ; chemistry ; toxicity ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; toxicity ; Arthritis, Rheumatoid ; drug therapy ; Chromatography, High Pressure Liquid ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Female ; Humans ; Male ; Mice ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Tandem Mass Spectrometry

The application of Aconitum herbs in the treatment of Bi syndrome has a long history and exact effects.By taking Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Preparata(Fuzi) as example, this study was aimed to mine the prescription rules of Aconitum herbs in the treatment of Bi syndrome, and provide thoughts and bases for modern clinical medication. 1 106 prescriptions were obtained in more than 20 classic books including medical, pharmacy, and synthesized books from Eastern Han dynasty to Qing dynasty. Based on the methods of frequency statistics, percentile statistics and Apriori algorithm of association rules, the characteristics of syndrome classification, dosage and compatibility of Aconitum herbs in the treatment of Bi syndrome were analyzed. The data-mining results indicated that 60.76% prescriptions contained Fuzi, which was obviously higher than Chuanwu or Caowu, and 17.63% contained two or more kinds of Aconitum herbs. 70.34% prescriptions were used mainly to treat Bi syndrome with wind-cold-wetness, others were for the syndrome with the deficiency of liver and kidney, blockage of phlegm and blood stasis, and wind-heat-wetness Bi. In the prescriptions with definite dose, 80% dosage of Fuzi was in the range from 0.29-2.14 g·d⁻¹, while the dosage of Chuanwu and Caowu was from 0.14-1.01g·d⁻¹, which was also affected by patterns, formulations and processing. The dose of Aconitum herbs was highest in the Bi syndrome with wind-cold-wetness, and its dose in the decoction and vinum was significantly higher than that in the pills and powders. The processed products were used in 93.11% prescriptions, and their dosage was higher than the raw ones. In the clinical treatment of Bi syndrome, Chuanwu and Caowu were often used with Saposhnikoviae Radix(Fangfeng), Liquiritiae Radix et Rhizoma(Gancao), Myrrha(Moyao) and Ephedrae Herba(Mahuang), while Fuzi was often used with Cinnamomi Cortex(Rougui), Achyranthis Bidentatae Radix(Niuxi), Fangfeng and Chuanxiong Rhizoma(Chuanxiong), which can both expel wind-dampness and relieve pain. All in all, Aconitum herbs are widely used in the treatment of Bi syndrome, which can relieve arthralgia and pain.
Aconitum ; chemistry ; Arthralgia ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Medicine, Chinese Traditional ; Pain Management ; Rhizome ; chemistry

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.
Aconitum ; chemistry ; toxicity ; China ; Data Mining ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Humans ; Medicine, Chinese Traditional

OBJECTIVETo study the effect of single administration of aqueous extracts from aconite on "dose-toxicity" relationship and "time-toxicity" relationship of mice hearts, through changes in electrocardiogram (ECG) and serum biochemical indexes.

METHODMice were grouped according to different drug doses and time points, and orally administered with water extracts from aconite for once to observe the changes of mice ECG before and after the administration, calculate visceral indexes heart, liver and kidney, and detect levels of CK, LDH, BNP and CTn-I in serum.

RESULTAccording to the "time-toxicity" relationship study, at 5 min after oral administration with aqueous extracts from aconite in mice, the heart rate of mice began rising, reached peak at 60 min and then slowly reduced; QRS, R amplitude, T duration and amplitude and QT interval declined at 5 min, reduced to the bottom at 60 min and then gradually elevated. The levels of CK, LDH, BNP and CTn-I in serum elevated at 5 min and reached the peak at 60 min, with no significant change in ratios of organs to body at different time points. On the basis of the "dose-toxicity" relationship, with the increase in single dose of aqueous extracts from aconite, the heart rate of mice. QRS, T duration and amplitude and QT interval declined gradually, and levels of CK, LDH, BNP and CTn-I in serum slowly elevated, with a certain dose dependence and no significant change in ratios of organs to body in mice.

CONCLUSIONSingle oral administration of different doses of aqueous extracts from aconite could cause different degrees of heart injury at different time points, with a certain dose dependence. Its peak time of toxicity is at 60 min after the administration of aqueous extracts from aconite.

Aconitum ; adverse effects ; chemistry ; Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; toxicity ; Female ; Heart ; drug effects ; physiology ; Heart Rate ; drug effects ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Mice

The diarrheal rat model was established by orally administering senna. The preventive experiment was concurrent for 6 days. The treatment experiment modeling had lasted for 12 days. The administration started at the 7th day, and lasted for 6 days. During the experiment, efforts were made in symptom score and weighing. After the experiment, hearts, livers, spleens, kidneys, brains, adrenals and thymuses were collected and weighed, lactic dehydrogenase (LDH) and cardiac troponin-I (cTn-I) in serum were detected. The efficacy of aqueousextracts from Aconiti Lateralis Radix Praeparata in preventing and treating rats with diarrheal and its accompanying toxicity were respectively studied. The result shows that aqueous extracts from Aconiti Lateralis Radix Praeparata could improve syndromes of rats with diarrheal. The 50% effective doses (ED50) of preventive and treatment administrations were 1.420 4 g · kg(-1) and 1.048 9 g · kg(-1), respectively. Aqueous extracts from Aconiti Lateralis Radix Praeparata could decrease the ratio of heart to body weight, and increase serum LDH and cTn-I. It was concluded that aqueous extracts from Aconiti Lateralis Radix Praeparata had a specific preventive and treatment effect on rats with diarrheal caused by senna, but with specific toxicity on heart.
Aconitum ; adverse effects ; chemistry ; Animals ; Body Weight ; drug effects ; Diarrhea ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Heart ; drug effects ; Humans ; Male ; Plant Roots ; adverse effects ; chemistry ; Rats ; Rats, Wistar ; Spleen ; drug effects

Sini decoction (SND), a classical traditional Chinese medicine emergency formula recorded in Shanghan Lun (Treatise on Febrile Diseases), which is composed of Aconiti Lateralis Preparata Radix, Glycyrrhizae Preparata Radix and Zingiberis Rhizoma. Modern clinical and pharmacological researches have shown that SND can protect the myocardium effectively during myocardial ischemia reperfusion injury (MI-RI). A myocardial ischemia reperfusion injury model of H9c2 cardiomyocytes in vitro has been established. Four groups, control group, MI-RI Model group, SND group and SND without Glycyrrhizae Radix group, were arranged. The livability, the level of LDH and CK activity in H9c2 cardiomyocytes in different groups were tested. By combining with principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares projection of latent structures-discriminant analysis (OPLS-DA), 17 biomarkers in extracellular fluid were identified and 15 of them were related to the pathway of biological processes. The results showed that the attenuate and synergistic mechanism between Aconiti Lateralis Praeparata Radix and Glycyrrhizae Radix for toxicity reduction was related with the glycolysis, lipid metabolism, citrate cycle and nitrogen metabolism of amino acids metabolism. The study proved the effect on H9c2 cardiomyocyte treated by MI-RI injury both SND group and SND without Glycyrrhizae Radix group, and compared with the SND without Glycyrrhizae Radix, the protective effect of myocardial ischemia reperfusion injury model of H9c2 cardiomyocyte from SND was stronger.
Aconitum ; chemistry ; Animals ; Drug Synergism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Glycyrrhiza ; chemistry ; Humans ; Male ; Metabolomics ; Myocardial Reperfusion Injury ; drug therapy ; genetics ; metabolism ; Myocytes, Cardiac ; drug effects ; Rats, Sprague-Dawley

OBJECTIVETo study the effect of Aconiti Radix Cocta and Pinelliae Rhizoma with different matching proportions and doses on their analgic, anti-inflammatory, phlegm eliminating and cough relieving efficacies in mice.

METHODThe two-factor, seven-level uniform design method was adopted to observe the effect of the oral administration with the combined decoction on the analgic, anti-inflammatory, phlegm eliminating and cough relieving efficacies, with frequency of body torsions induced by acetum, ear swelling degree induced by dimethylbenzene, secretion of phenol red in tracheas and frequency of coughs induced by aqueous ammonia as indexes. Significant matching proportions and doses were collected for verification.

RESULT(1) The effect on the frequency of body torsions and ear swelling degree. The combined decoction could effectively reduce the frequency of body torsions and ear swelling degree. According to a regression analysis, Aconiti Radix Cocta and Pinelliae Rhizoma had the antagonism, which was maximized at the ratio of 10: 1, and minimized at the ratio of less than or equal to 1: 1. The frequency of body torsions and ear swelling degree increased first and then decreased along with the rise in the total dose; and a higher proportion of Aconiti Radix Cocta resulted in a faster speed in decrease or increase. (2) The effect on the secretion of phenol red in tracheas and frequency of coughs. The combined decoction could effectively increase the secretion of phenol red in tracheas and decrease the frequency of coughs. According to a regression analysis, Pinelliae Rhizoma and Aconiti Radix Cocta had the synergistic effect in the secretion of phenol red in tracheas, which was maximized with a total dose of more than 5 g x kg(-1) and a ratio of 1: 1.

CONCLUSIONThe compatible application of Pinelliae Rhizoma and Aconiti Radix Cocta can decrease the analgesic and anti-inflammatory effects of Aconiti Radix Cocta and promote the cough-relieving effect of Pinelliae Rhizoma, which vary according to different matching ratio and dose. This study provides experimental basis for indepth studies on the combined effect of Aconiti Radix Cocta and Pinelliae Rhizoma--two of eighteen incompatible pairs.

Aconitum ; Animals ; Cough ; drug therapy ; Drug Therapy, Combination ; Male ; Mice ; Mice, Inbred ICR ; Pinellia ; Plant Extracts ; administration & dosage ; Research Design

The paper is to report the study of the effect of Shenfu injection on the enzyme activity of liver CYP450 and its mRNA level of rat liver. Microsome of rat liver was prepared after intravenous administration of Shenfu injection for 7 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA expression of CYP1A2, CYP2B1/2, CYP2C11 and CYP3A1 in the liver was detected by RT-PCR. Shenfu injection obviously induced the enzyme activities of CYP2B and CYP2C. Meantime Shenfu injection decreased the enzyme activities of CYP1A2 and CYP3A. The mRNA levels of CYP2B and CYP2C were also induced in rats treated with Shenfu injection. But it obviously inhibited the mRNA level of CYP1A2 and CYP3A. Since the enzyme activity and mRNA level were obviously changed after administration, the potential effect of drug-drug interaction should be concerned.
Aconitum ; chemistry ; Animals ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Cytochrome P-450 CYP2B1 ; genetics ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Cytochrome P450 Family 2 ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Injections ; Male ; Microsomes, Liver ; enzymology ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Steroid 16-alpha-Hydroxylase ; genetics ; metabolism

OBJECTIVETo study Chinese medicine (CM) signs and symptoms of urethane-induced lung cancer in mice, and observe the effect of Aconiti Lateralis Radix Praeparata and Taraxaci Herba on symptoms in mice and tumor progress.

METHODThe mice were intraperitoneally injected with urethane twice a week for consecutively five weeks to establish a lung cancer model. The changes in their appearance, body temperature and auricle microcirculation were observed in carcinogenic process. CM signs and symptoms of urethane-induced lung cancer in mice were evaluated with energy metabolism, erythrocytic ATP emzymatic activity and hemorrheological index. During the tumor model was induced, Aconiti Lateralis Radix Praeparata and Taraxaci Herba were used to treat the mice and observe their effect on symptoms in mice and tumor progress.

RESULTDuring urethane was used to induce lung cancer, the mice had gradually become chill, lazy, hunched, with reduction in temperature, cyanosis in auricle and tail. Meanwhile, their energy metabolism and erythrocytic ATP enzymatic activity reduced, whereas their whole blood viscosity and erythrocytic aggregate index increased. Taraxaci Herba showed an effect on enhancing above symptoms and signs but had no effect on tumor progress. Aconiti Lateralis Radix Praeparata showed an effect on reducing above symptoms and signs and preventing tumor progress.

CONCLUSIONMice with urethane-induced lung cancer show CM signs and symptoms of congealing cold with blood stasis. The treatment with Aconiti Lateralis Radix Praeparata can alleviate symptoms and signs in mice and prevent tumor progress.

Aconitum ; chemistry ; Animals ; Blood Circulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Lung Neoplasms ; chemically induced ; drug therapy ; pathology ; physiopathology ; Mice ; Mice, Inbred BALB C ; Neoplastic Processes ; Taraxacum ; chemistry ; Urethane ; adverse effects

OBJECTIVETo study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects.

METHODSForty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature (TT), energy intake (EI), digestible energy (DE), and metabolizable energy (ME) were measured. The content of adenosine triphosphate (ATP) and energy charge (EC) in hepatic tissue were measured with high performance liquid chromatography (HPLC). The activity of ATPase and succinate dehydrogenase (SDH) in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina's rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of results.

RESULTSCompared with the control group, the TT on the 10(th) day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly (P<0.05). EI/body mass (BM), DE/BM, ME/BM, the hepatic EC and the activity of Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group (P<0.05). There were 592 differential expression genes in the Radix aconiti lateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group.

CONCLUSIONSHerbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.

Aconitum ; chemistry ; Adenosine Triphosphatases ; metabolism ; Adenosine Triphosphate ; metabolism ; Animals ; Body Temperature ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Energy Intake ; drug effects ; genetics ; Energy Metabolism ; drug effects ; genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Rhizome ; chemistry ; Succinate Dehydrogenase ; metabolism