Comparison of alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata based on UHPLC-Q-Exactive Orbitrap MS/MS / 中国中药杂志

UHPLC-Q-Exactive Orbitrap MS/MS was used to systematically analyze and compare the alkaloids in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata. After the samples were pretreated in the solid-phase extraction cartridges, 0.1% ammonium hydroxide(A)-acetonitrile(B) was used for gradient elution. The LC-MS method for characterization of alkaloids in the three herbal medicines was established in ESI positive ion mode to collect high resolution MS data of reference substances and samples. On the basis of the information of reference substance cracking behavior, retention time, accurate molecular mass, and related literature, a total of 155 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Prae-parata. Specifically, 130, 127, and 92 alkaloids were identified in Aconiti Kusnezoffii Radix, Aconiti Radix, and Aconiti Lateralis Radix Praeparata, respectively. Monoester alkaloids and amino-alcohol alkaloids were dominant in the three herbal medicines, and the alkaloids in Aconiti Kusnezoffii Radix and Aconiti Radix were similar. This paper can provide a reference for elucidating the pharmacological effects and clinical application differences of the three herbal medicines produced from plants of Aconitum.

Metabolic regulation mechanism of Aconiti Radix Cocta extract in rats based on / 中草药·英文版

Objective: To establish a metabonomics research technique based on the combination of

Effects of Different Processed Methods on Anti-gouty Arthritis and Cardiotoxicity of Aconiti Radix / 中国实验方剂学杂志

Objective:To study the effects of different processing methods on the anti-gouty arthritis and cardiotoxicity of Aconiti Radix， and to explore the possible attenuation and synergism mechanism of these different processing methods. Method:The swelling degree of knee joint， levels of inflammatory factors ［interleukin （IL） -1<italic>β</italic>， IL-18， tumor necrosis factor （TNF）-<italic>α</italic>］ and the activities of liver energy metabolism-related enzymes ［Ca²⁺-Mg²⁺-adenosine triphosphatase （ATPase）， Na⁺-K⁺-ATPase， succinate dehydrogenase （SDH）］ in rats with gouty arthritis were used as indicators to evaluate the effects of pharmacopoeia steaming Aconiti Radix， pharmacopoeia boiling Aconiti Radix， Jianchang faction processed Aconiti Radix， Zhang faction processed Aconiti Radix and raw Aconiti Radix. The activity of creatine kinase （CK）， lactate dehydrogenase （LDH） and the content of B-type natriuretic peptide （BNP） were used as indexes to evaluate the cardiotoxicity of Aconiti Radix and its different processed products. Result:In the anti-gouty arthritis test， compared with the blank group， the knee joint of the model group was significantly swollen （<italic>P</italic><0.01）， the levels of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> in serum were significantly increased （<italic>P</italic><0.01）， and the Ca²⁺-Mg²⁺-ATPase activity was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， raw Aconiti Radix and the four processed products could reduce knee joint swelling and decrease IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> levels in serum of rats. The activity of Ca²⁺-Mg²⁺-ATPase in the liver of rats from the pharmacopoeia steaming Aconiti Radix group was significantly higher than that in the model group （<italic>P</italic><0.01）， and there was no statistical difference in other groups. In the cardiotoxicity test， compared with the blank group， the activities of CK and LDH were significantly increased and the level of BNP was significantly increased in the raw Aconiti Radix group and the pharmacopoeia steaming/boiling Aconiti Radix groups （<italic>P</italic><0.01）. In terms of LDH activity and BNP content， the Zhang faction and Jianchang faction processed Aconiti Radix groups were significantly lower than those in the raw Aconiti Radix group （<italic>P</italic><0.01）. In the CK activity， the Zhang faction processed Aconiti Radix group was significantly lower than that in the raw Aconiti Radix group （<italic>P</italic><0.01）. Conclusion:Raw Aconiti Radix and the four processed products have certain anti-inflammatory effects， but there are some differences among different indicators. There are significant differences in cardiotoxicity between the raw products and processed products of Aconiti Radix， and the cardiotoxicity of Jianchang faction and Zhang faction processed products was the weakest.

Research Progress on Multi-material and Multi-process Processing of Aconiti Radix / 中国实验方剂学杂志

Aconiti Radix is a kind of medicinal material with great toxicity, which has more than 2 000 years of clinical application history, in the folk, there are often poisoning accidents caused by improper processing. The main processing purpose of Aconiti Radix in the early period was to reduce the toxicity with simple procedure and single excipient. Since the Song dynasty, with the deepening of physicians' cognition of processing and the theory of medicinal properties, the application of procedures and materials in the processing of Aconiti Radix began to become complicated, and the scope of clinical application was further expanded. In modern times, the processing technology of Aconiti Radix is mainly based on steaming and boiling, which is quite different from the traditional processing method with multiple materials and multiple processes. Based on the characteristics of many kinds of materials and processes, this paper discusses the change in processing methods of Aconiti Radix from the perspective of excipients and processes, as well as modern processing research, in order to lay a scientific foundation for exploring the effects of many kinds of materials and processes on the quality of Aconiti Radix and revealing its processing mechanism, and provide basis and reference for establishing a more reasonable and scientific processing method for Aconiti Radix in the future.

Investigation on molding process and compatibility-synergistic mechanism of Aconiti Radix-Zanthoxyli Pericarpium volatile oil gel patch / 中草药

Objective: To optimize the forming process of gel patch and explore the compatibility-synergistic mechanism of Aconiti Radix-Zanthoxyli Pericarpium volatile oil gel patch. Methods: According to the indexes of skin followability, disclosing ability, initial adhesion and peeling degree, the substrate-property of eight commercially gel patches was evaluated. Then, with the comprehensive sensory evaluation, initial adhesion, stickiness and peeling degree as the index, single factor experiment and mixture design experiment were used to screen the proportion of matrix excipients of gel patch. Taking the number of acetic acid-induced writhing in mice as the index, the drug loading of gel paste was screened by in vivo animal evaluation. In addition, the compatibility effect of Aconiti Radix-Zanthoxyli Pericarpium volatile oil gel patch was studied by using formaldehyde-induced pain model and metabolomics. Results: Different brands of gel plaster had great difference in their skin followability, disclosing ability, initial adhesion and peeling degree. The initial adhesion and peel degree of gel patch had great influence on its disclosing ability and the greater the initial adhesion and peel degree were, the worse disclosing ability was. The matrix of the Aconiti Radix gel patch was 3% polyacrylic acid sodium NP700, 1.5% carboxymethyl cellulose sodium, 0.25% Carbomer, 0.06% crystalline aluminum chloride, 0.1% ethylenediamine tetra acetic acid two sodium, 26% glycerol, 61.5% water, 4% diatomaceous earth, 0.15% tartaric acid; Drug dosage of each gel patch was 560 mg extracts of Aconiti Radix. Zanthoxyli Pericarpium olatile oil could enhance the analgesic effect of Aconiti Radix gel patch, which might be mainly through glycerol phospholipid metabolism and linoleic acid metabolism. Conclusion: To ensure better adherence and disclosure of gel patch, the initial adhesive force of gel patch should be controlled between 7-18 balls and the peel degree should be controlled between 0.03-0.97 kN/m. The Prepared Aconiti Radix gel patch has a good appearance, adhesion and shape with a clear analgesic effect, and Zanthoxyli Pericarpium olatile oil can enhance analgesic effect of Aconiti Radix gel patch. This study provides a basis for the development and application of new preparations for the external use in Aconiti Radix.

Changes of processing process of Aconiti Radix Cocta based on bionic technology / 中草药

Objective: To study the characteristics of gas and taste changes in different stages during the processing of Aconiti Radix Cocta (ARC), and characterize the relationship between the changes of gas and taste and the internal active components. Methods: The changes of gas and taste of three batches of ARC samples with different processing time were detected by using electronic nose and electronic tongue system, the obtained data from processing were analyzed through the radar map, linear discriminant analysis (LDA), principal component analysis (PCA), and the correlation analysis was made with alkaloids from ARC processing. Results: Electronic nose and electronic tongue could distinguish the samples of different processing degree of ARC. Pearson correlation analysis showed that electronic nose FAC1 was significantly correlated with aconitine, neoaconitine, benzoylaconitine, benzoylneoaconitine and monoester alkaloids (P < 0.01). Electronic tongue FAC2 was significantly correlated with the total amount of benzoylaconitine and monoester alkaloids (P < 0.01), and correlated with the content of benzoylaconitine (P < 0.05). Conclusion: The bionic technology of electronic nose and electronic tongue could be used to study the processing quality of ARC. This method provides a new way of thinking for the Chinese medicine processing study.

Anti-arthritic-related metal bioavailability for optimal compatibility ratio of Aconiti Radix Cocta and Paeoniae Radix Alba / 中国中药杂志

Trace metals deficiency or excess are associated with the etiology and pathogenesis of rheumatoid arthritis(RA). Aconiti Radix Cocta(A) and Paeoniae Radix Alba(B) are commonly used together for the treatment of RA. In this study, we aim to determine anti-arthritic-related metal bioavailability in the compatibility of herb A and B for avoiding metal deficiency or excess, and optimize the combination ratio of herb A and B, accordingly. Anti-arthritic-related metal bioaccessibility were evaluated by in vitro simulator of all gastrointestinal tract(including mouth, stomach, small and large intestines), and the roles of gastrointestinal digestive enzymes and intestinal microflora were investigated. Anti-arthritic-related metal bioavailability was assessed by the affinity adsorption with liposomes. The results indicated that compatibility proportion of corresponding herbal plants, gastrointestinal digestion and microbial metabolic, which could affect metal digestion and absorption. The optimal compatibility proportion of 1 A∶1 B is recommended, according to the dose of anti-arthritic-related metal bioavailability, which is often chosen for clinical practice of RA therapy. Thus, anti-arthritic-related metal bioavailability might be the key active substances for RA treatment.

Research advancement in mechanisms of processing and compatibility for detoxication of Aconitums / 中国中药杂志

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.

Chemical components and pharmacological action of Aconiti Radix / 中国中药杂志

Aconiti Radix is a commonly used traditional Chinese medicine( TCM) herb in clinic,with the effects in expelling wind and removing damness,warming menstruation and relieving pain. With a long medicinal history and high medicinal value,it was used for anemofrigid-damp arthralgia,arthralgia,cold hernia and anesthesia analgesia. Modern pharmacological studies have shown that Aconiti Radix has a good therapeutic effect on rheumatoid arthritis,neuropathic pain and hypertension. As a well-known toxic TCM herb,its main pharmacodynamic and toxic components are alkaloids,which can lead to neurotoxicity and cardiotoxicity while exerting anti-inflammatory,analgesic,anti-tumor and other pharmacodynamic effects. Therefore,it is often processed to reduce its toxicity or combined with Paeoniae Radix Alba and Stephaniae Tetrandrae Radix to achieve the purpose of reducing toxicity and increasing efficacy in clinic.In recent years,with the deepening of the study on the incompatibility of TCM represented by " eighteen incompatible herbs",there have been new findings about TCM incompatibility. It has been found complementary effect,rather than no obvious toxic and side effects after the combination with incompatible herbs of Aconiti Radix. To provide the basis for further study and clinical application of Aconiti Radix,this paper reviewed chemical components,pharmacological action,toxicity and compatibility of Aconiti Radix by consulting relevant literatures published in recent years at home and abroad. Meanwhile,this paper also described the relationship between chemical constituents,as well as anti-inflammatory,analgesic,anti-tumor and other pharmacological effects and toxicity.

Comparative study on six alkaloids in Aconiti Lateralis Radix Praeparata and Aconiti Radix in Jiangyou of Sichuan Province based on multivariate statistical analysis / 中草药

Objective: To establish a UPLC method for the simultaneous determination of benzoylmesaconitine, benzoylaconitine, benzoylhypaconitine, mesaconitine, hypaconitine and aconitinein Aconiti Lateralis Radix Praeparata (ALRP) and Aconiti Radix (AR), and to compare the content difference of six alkaloids in the samples with multivariate statistical analysis. Methods Alkaloids in ALRP and AR were extracted with 0.05 mol/mL hydrochloric acid solution by ultrasonic extraction. The UPLC method was performed on a BEH C18 (100 mm × 2.1 mm, 1.7 μm) through a gradient elution of acetonitrile and water at a flow rate of 0.1 mL/min with column temperature at 35 ℃. The injection volume was set at 4.0 μL, and the detection wavelength was set at 235 nm. Difference significance analysis, activity ratio analysis, toxic constituents index analysis, correlation analysis, hierarchical cluster heatmap analysis, principal component analysis, and TOPSIS analysis were used for data processing to comprehensively evaluate the quality of ALRP and AR. Results The method was in accordance with the regulations. Compared with the content of six alkaloids in ALRP and AR, significant difference existed in mesaconitine, benzoylhypaconitine, aconitine, and monoester diterpenoid alkaloids (MDAs); Significant difference existed in benzoylmesaconitine and benzoylaconitine; There were no significant difference in hypaconitine and diester-diterpenoid alkaloids (DDAs). Taking the six alkaloids as indexes, the sample No. 15 of ALRP was the best in quality and the samples No. 7 of AR was the best in quality. Conclusion The established method is simple, accurate and reliable with good precision, repeatability and stability, which can be used for the simultaneous determination of six alkaloids in ALRP and AR. It is much more accurate and convenient to conduct the quality evaluation by using activity ratio, toxic constituents index and multivariate statistical analysis. The study could provide a reference for improving analysis and determination of ester-type alkaloids in ALRP and AR in ChP, and providing a reference for quality control and evaluation of ALRP and AR.

Dynamic changes of alkaloids in growth cycle in stems and leaves of Aconitum carmichaelii by HPLC-MS/MS / 中草药

Objective: To investigate the content changes of alkaloids in stems and leaves of Aconiti Radix at different growth period. Methods: The Phenomenex C18 column (150 mm × 4.6 mm, 5 μm) was used and 0.1% formic acid aqueous solution-acetonitrile was selected as mobile phase; The mass spectrum was scanned by ESI+ multiple reaction monitoring (MRM) mode. The HPLC-MS/MS method was established for the simultaneous determination of aconitine, mesaconitine, hypaconitine, indaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconitine, aconine, fuziline, neoline, talatisamine, songorine, higenamine, and salsoline in the stems and leaves of Aconite Radix. Combined with principal component analysis (PCA), the transfer rule of various alkaoids was tracked in the growth cycle of Aconiti Radix. Results: Methodological validation results showed that the linear range of the 14 compounds was good (r2 > 0.990 0). The limit of quantification was 2.27-18.27 ng/mL, and the average recovery was 94.73%-104.50%. The results showed that there was considerable amounts of alkaloids in stems and leaves of Aconiti Radix, and the total contents of alkaloids in stems were higher than those in leaves. In May, June, July, and August, the total content of alkaloids in stems was 0.087 1%, 0.182 8%, 0.141 0%, and 0.199 4% respectively, which showed a wave-like upward trend. The total content of alkaloids in leaves was 0.074 7%, 0.075 9%, 0.081 4%, and 0.058 9% respectively, which showed a trend of rising first and then decreasing, and the total content of alkaloids in leaves was highest in July. Conclusion: PCA found that the alkaloids content in stems and leaves showed different variation trend in the different period. The considerable alkaloids in stems reached the peak value at the harvest time. The amount of alkaloids is considerable, which has the potential and development value of becoming new medicinal resources.

Feasibility Analysis of Removal of Alkaloids from Processing Wastewater of Aconiti Radix by Flocculation / 中国实验方剂学杂志

Objective: To investigate the removal effect of 5 kinds of common flocculants on 6 kinds of toxic alkaloids in processing wastewater of Aconiti Radix. Method: HPLC was employed to determine contents of 6 kinds of alkaloids in the processing wastewater of Aconiti Radix before and after flocculation.The mobile phase consisted of acetonitrile-tetrahydrofuran(25:15)-0.1 mol·L-1 ammonium acetate solution(each 1 L contains 0.5 mL of glacial acetic acid) for gradient elution, volume flow rate was 1.0 mL·min-1, detection wavelength was 235 nm.The removal characteristics and effects of five common flocculants of ferric chloride, aluminum sulfate, polymeric ferric sulfate, polyaluminum chloride/polyacrylamide(PAC/PAM) and sodium polyacrylate were compared and preliminarily optimized. Result: The 5 kinds of flocculants had certain selectivity for different types of alkaloids, and the removal of 6 kinds of alkaloids showed obvious differences.Among them, the PAC/PAM attenuated relative superiority, when the pH 6, adding amount of 0.25 g·L-1 and PAC-PAM dosing ratio of 30:1, comprehensive removal effect was relatively good, removal rates of mesaconitine and hypaconitine was 85.4%and 58.3%, respectively. Conclusion: The flocculation method can be used as a pretreatment process to reduce the toxicity of processing wastewater of Aconiti Radix.

Recovery and Utilization of Alkaloids in Processing Wastewater of Aconiti Radix / 中国实验方剂学杂志

Objective: To optimize the recovery technology for 6 kinds of toxic alkaloids in the toxic wastewater from processing of Aconiti Radix with macroporous resin. Method:With the rates of adsorption and elution of benzoylmesaconine,benzoylaconine,benzoylhypaconine,mesaconitine,hypaconitine and aconitine as indexes,static and dynamic adsorption-elution tests were used to select the best one from 15 kinds of macroporous resin,and the recovery technology parameters of six toxic alkaloids in the wastewater from processing of Aconiti Radix were optimized. Result:D101 macroporous resin had a good adsorption and elution effect on 6 kinds of toxic alkaloids in the wastewater from processing of Aconiti Radix,its optimum technology conditions were as follows:each gram of macroporous resin could be used to treat processing wastewater from 4.3 g of Aconiti Radix,the sample loading speed was not higher than 3.0 mL·min-1,the resin column was eluted with 6 BV of 70% ethanol after removing impurities with 2 BV of water.The recoveries of benzoylmesaconine,benzoylaconine,benzoylhypaconine,mesaconitine, hypaconitine and aconitine were 98.03%,94.09%,96.53%,78.15%,85.40% and 70.57%,respectively. Conclusion:D101 macroporous resin can be used for detoxification treatment of processing wastewater of Aconiti Radix,at the same time,6 kinds of alkaloids are effectively recovered,which can solve the environmental problems and create certain economic benefits,and the optimized process conditions are stable and feasible.

Pharmacological Evaluation for Extracts of Aconiti Radix and Aconiti Radix Cocta / 中国实验方剂学杂志

Objective: To carry out the studies of pharmacological action for extracts of Aconiti Radix and Aconiti Radix Cocta, and evaluate the selection of raw materials in prescriptions, in order to promote the development and clinical application of preparations. Method: The mixed extracts of Aconiti Radix and Aconiti Radix Cocta were prepared respectively according to the technique of aconitum injection, and different dose groups of Aconiti Radix and Aconiti Radix Cocta were established based on the dose of Aconiti Radix 0.152 5 mg·g-1, and then applied in such pharmacodynamic tests as analgesia, heart rate reduction, antitumor effect and toxicology tests, such as acute toxicity and organ observation. The data were analyzed systematically on the basis of literatures. Result: Compared with blank group, the extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly analgesic effect. At the same dose, the pain inhibition rate of Aconiti Radix injection (60.91%) was higher than that of Aconiti Radix Cocta injection (53.42%), and the pain inhibition rate of Aconiti Radix extract for oral administration(73.94%) was also much higher than that of Aconiti Radix Cocta extract (29.97%), with significant differences (Pth min after administration, the heart rate of the Aconiti Radix group was decreased first, then stabilized, and finally increased with the rise of the dose, while for the Aconiti Radix Cocta group showed a different trend of first stability, then decrease and finally increase. The result indicated the Aconiti Radix group had the effect in reducing heart rate in rats at a low dose. The survival inhibition rate was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The extracts of both Aconiti Radix and Aconiti Radix Cocta had a significantly inhibitory effect on the proliferation of AGS gastric cancer cells, in which Aconiti Radix was stronger than that of Aconiti Radix Cocta at the same dose. In the acute toxicity test of rats, lethal dose 50%(LD50) of Aconiti Radix and Aconiti Radix Cocta were 3.9 g·kg-1 and 21.0 g·kg-1 respectively, which were equivalent to 4 times and 20 times of the clinical dose. LD50 of the extract of Aconiti Radix Cocta was 5 times than that of Aconiti Radix. The liver and kidney of dead rats were dark with obvious symptoms of poisoning after dissection, while all the organs of rats at the clinical and lower dose were normal. Conclusion: The safety of Aconiti Radix is lower than that of Aconiti Radix Cocta, but with greater analgesic, bradycardic and anticancerous effect. Therefore, it is suggested that the preparations, such as aconitum injection, should be prepared with Aconiti Radix in the treatment of severe pain of patients with advanced gastric and liver cancer, and the preparations for general pain can be prepared with Aconiti Radix Cocta, so as to achieve a truly safe and effective dialectical treatment.

Determination and multivariate statistical analysis of four nucleosides in Aconiti Lateralis Radix praeparata and Aconiti Radix in Jiangyou of Sichuan Province / 中草药

Objective To establish a UPLC method for the simultaneous determination of uracil, adenosine, guanosine, and uridine in Aconiti Lateralis Radix Praeparata (ALRP) and Aconiti Radix (AR), and to compare the content difference of four nucleosides in the samples based on multivariate statistical analysis. Methods Nucleosides in ALRP and AR were extracted with purified water by ultrasonic extraction. The UPLC method was performed on a BEH C18 (100 mm × 2.1 mm, 1.7 μm) through a gradient elution of acetonitrile and water at a flow rate of 0.2 mL/min with column temperature at 30 ℃. The injection volume was set at 4.0 μL, and the detection wavelength was set at 260 nm. Difference significance analysis, hierarchical cluster heatmap analysis, principal component analysis, and TOPSIS analysis were used for data processing to comprehensively evaluate the quality of ALRP and AR. Results The method was in accordance with the regulations, the quantitative evaluation of uracil, adenosine, guanosine, and uridine was in good linear range (r2 > 0.999 3), and the average recovery was 99.86%, 99.14%, 99.74%, and 98.71% respectively, and the RSDs were all less than 2.0%. Taking the four nucleosides as indexes, the samples No. 18 of ALRP and the samples No. 23 of AR were the best in quality. Conclusion The established method is simple, accurate, and reliable with good precision, repeatability, and stability, which can be used for the simultaneous determination of four nucleosides in ALRP and AR, and it might provide the scientific basis for the study of water-soluble constituents in ALRP and AR.

Cardiotoxicity and neurotoxicity features of Aconiti Radix ethanol extract and its impacts on vascular endothelial / 中草药

Objective: To investigate the features of cardiotoxicity and neurotoxicity and the influence on vascular endothelial of ethanol extract of Aconiti Radix (AR). Methods: Totally 45 Wistar rats were randomly divided into four groups, and ig given low-, middle-, and high-dose 70% ethanol extract of AR (in the raw drug dose of 2.5, 5.0, and 7.5 g/kg respectively) for 15 d. The toxic reaction and death condition were observed during administration. The electrocardiogram (ECG) change was tested after administration. Blood was collected for blood routine and blood biochemistry analysis. Brain was harvested for calculating viscera index and pathological examination. Left ventricular and hippocampus were extracted and stained with electron microscope (EM) methods. Results: At the end of treatment, all rats were sacrificed in the high-dose AR group. The mortality and hematologic parameters including RBC, HGB, HCT, ALT, UREA, and GLU were significantly increased in the middle-dose AR groups compared with control group. Arrhythmia especially ventricular arrhythmia occurred in low- and middle-dose AR group. Brain index and number of pyknotic neurons in focal area of hippocampus were significantly increased in middle-dose AR group. EM examination indicated that dissolution of neuronal inclusions, nuclear fragmentation, and coagulation necrosis of glial cells were prominent in the hippocampus tissue in middle-dose AR group. In the middle-dose AR group, the vascular endothelial cells injury and apoptosis were obviously observed in left ventricular and hippocampus separately. Conclusion: The ethanol extract of AR can lead to cardiotoxicity and neurotoxicity especially vascular endothelial injury in dose-dependent manner.

Anti-inflammatory mechanism analysis of antirheumatic Chinese medicinal herb Aconiti Radix based on protein interaction network / 中国中药杂志

Inflammation is one of the important risk factors of rheumatic diseases. Aconiti Radix is widely used for the treatment of rheumatism, which has significant anti-inflammatory effects. However, its anti-inflammatory mechanism on molecular level is still not clear. The purpose of this study is to illuminate the anti-inflammatory mechanism of Aconiti Radix based on the protein interaction network (PIN) analysis on molecular network level. The main anti-inflammatory components (aconitine, hypaconitine and mesaconitine) were chosen in this study to obtain the targets of the components and protein-protein information though databases retrieval and construct the PIN of Aconiti Radix. By a graph theoretic clustering algorithm molecular complex detection(MCODE), 13 modules were identified and analyzed by gene ontology(GO) enrichment. The results showed that the anti-inflammatory mechanism of Aconiti Radix was mainly associated with prostanoid metabolic process and leukocyte chemotaxis mediated by chemokines. In this study, the anti-inflammatory mechanism of Aconiti Radix was elucidated systematically from molecular network level, which provided the scientific basis for the treatment of rheumatic diseases.

Effects of combined administration of Paeoniae Radix Alba on local pharmacokinetics of six aconite alkaloids by skin microdialysis in vivo / 中国中药杂志

The Aconiti Radix Cocta gel and Aconiti Radix Cocta combined with Paeoniae Radix Alba gel were administered to mice. Physiological saline was taken as perfusate. The perfusion rate was 2 μL•min⁻¹ and the microdialysis samples were collected every 0.5 h intervals for eight times. The six aconitine alkaloids concentration in perfusate were determined by HPLC-MS/MS. The concentration-time curves were plotted, and the pharmacokinetic parameters were calculated and analyzed by SPSS. The effects of Paeoniae Radix Alba on transdermal permeation role of six aconitine alkaloids in herb couple of Paeoniae Radix Alba-Aconiti Radix Cocta were investigated. According to the results, Tmax of the three mono-ester aconitum alkaloids of Aconiti Radix Cocta combined with Paeoniae Radix Alba groups were shortened, meanwhile, Cmax and AUC of benzoylaconine and benzoylhypaconine were increased. However, AUC of the three diester-type alkaloids were reduced, with Tmax of hypaconitine prolonged and Cmax lowered. The study suggested that the combined administration of Aconiti Radix Cocta and Paeoniae Radix Alba promoted the transdermal permeation of mono-ester aconitum alkaloids, and inhibited the absorption of parts of diester-type alkaloids. This study proved the decreasing toxicity and increasing efficacy of the combination of Aconiti Radix Cocta and Paeoniae Radix Alba on the transdermal permeation, and provided a reference for studies on the prescription combination regularity and relevant practices.

Effect of starch composition on dissolution of alkaloids in Aconiti Radix co-decocted with Pinelliae Rhizoma or Ampelopsis Radix / 中草药

Objective: To analyze the effect of starch composition on the dissolution of small molecular alkaloids in Aconiti Radix when co-decocted with medicines rich in starch, and to explore the mechanism of the effect of starch on alkaloids. Methods: RRLC-Q- TOF-MS was used to analyze the effect of starch on the dissolution of alkaloids in the decoctions. HPLC-UV was applied to determine the content of alkaloids in the decoctions of starches with alkaloids, and analysis of variance and partial least square method were used to analyse the difference. Results: The dissolution of alkaloids in Aconiti Radix, including the diester-, monoester-, and amine- diterpenoid alkaloids, wsa obviously decreased when co-decocted with starch, especially the monoester- and amine-diterpenoid alkaloids co-decocted with Pinelliae Rhizoma, Ampelopsis Radix, starch of Pinelliae Rhizoma, starch of Ampelopsis Radix, and normally sold starch, while the content of diester-diterpenoid alkaloids was increased when co-decocted with starch-removed Pinelliae Rhizoma and Ampelopsis Radix. When co-decocted directly with starch, free alkaloids in water decoction was decreased compared with the decoction without starch. Conclusion: Starch could inhibit the dissolution of alkaloids in Aconiti Radix in the decoction. Free Aconitum alkaloids could be integrated by the starch, which could finally affect their content in decoction.

Simultaneous determination of six alkaloids in Aconitum plants by HPCE / 中国药学杂志

OBJECTIVE: To establish a high performance capillary electrophoresis (HPCE) method for simultaneous determination of aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine and benzoylmesaconine in the herbs from Aconitum plants.