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.

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.

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.

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 Ampelopsis Radix on dissolution of main chemical constituents in Aconiti Radix Cocta based on RRLC-Q-TOF-MS technology / 中草药

Objective: Under the guidance of eighteen antagonisms of Chinese materia medica, to analyze the effect of Aconiti Radix Cocta combined with Ampelopsis Radix in different ratios on the characteristic constituents and to explore the in vitro compatibility mechanism of Aconiti Radix Cocta and Ampelopsis Radix. Methods: A certain weight of Aconiti Radix Cocta was combined with various amounts of Ampelopsis Radix, and a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) method based on chemical profiling approach was used to determine the content of alkaloids in decoctions and sediments. The aconitine alkaloids were established and were subjected to PLS-DA and ANOVA to provide intergroup difference and distribution characteristics. In addition, the method of UV spectrophotometer was adopted to determine the content of starch and tannins in Ampelopsis Radix. Results: There were certain differences among each group, especially between the single Aconiti Radix Cocta and Aconiti Radix Cocta combined with Ampelopsis Radix at the ratio of 1:3. With the increasing of the ratio of Ampelopsis Radix in the combination, the content of alkaloids appeared to increase in the decoction while decrease in the sediment. After determination, the mass fractions of starch and tannic acid in Ampelopsis Radix were 25.44% and 0.31%, respectively. Conclusion: The aconitine alkaloids could be deposited with the starch in Ampelopsis Radix, meanwhile decreased in the decoction, which establishes the foundation for the further research on the chemical mechanism of Aconiti Radix Cocta combined with Ampelopsis Radix.

Rapid determination of monoester alkaloids in extraction and concentration process of Aconiti Radix Cocta by near infrared spectroscopy / 中草药

Objective: To rapidly and quantitatively analyze the monoester alkaloids (MAs) in the extracting and concentrating process of Aconiti Radix Cocta (ARC) by near infrared spectroscopy (NIR). Methods: Using NIR to collect the data of 103 ARC samples and using partial least squares (PLS) regression method to establish the quantitative analysis model of MAs between the information of NIR and MAs. Results: The spectral range of MAs model of ARC was 9 264.35-7 274.11 cm-1. The root mean square error of cross validation (RMSECV) was 1.171 and correlation coefficient (r) of the calibration model was 0.999 4.Through the external validation, the root mean square error of prediction (RMSEP) was 1.321 and r of the validation model was 0.992 1. According to the results of statistical analysis, r of the predicted value and the reference value of MAs was 0.999 0. The value of P is less than 0.001. This revealed that the NIR and HPLC methods had a good correlation in determining MAs and could accurately predict the amount of MAs in the covered range. Conclusion: This method is convenient, rapid, accurate, and environment protective, and could be used for the on-line determination of MAs in the extracting and concentrating process of ARC and for the determination of the extraction and concentration endpoint of ARC.

Optimization of microwave-assistant extraction technology for codecoction of Aconiti Radix Cocta coupled with Paeoniae Radix Alba / 中草药

Objective: To optimize the microwave extraction (ME) technology for extraction of total aconitum alkaloids and paeoniflorin in co-decoction of Aconiti Radix Cocta coupled with Paeoniae Radix Alba.. Methods: Orthogonal test with single factor, as well as ME method was used, 65% ethanol was optimized as extraction solvent, the effects of four factors, such as the microwave power, the radiation time, the solvent consumption, and ethanol concentration in microwave extraction process were investigated. The contents of total aconitum alkaloids were determined by UV-visible spectrophotometry and the paeoniflorin by HPLC by taking the contents and extract yield as evaluation indexes. Results: The optimum conditions of extraction were as follows: 65% ethanol as extracting solvent, the microwave power was 800 W, the radiation time was 0.5 h, the proportion of raw material to solvent was 1:10. In the condition, the highest extracting content and lowest extract yield of total aconitum alkaloids and paeoniflorin could be obtained. Conclusion: The optimized microwave extraction technology could be a potential way with the shorter time and higher extract yield and ME methods is better than the conventional extraction methods.