Radix Aconiti Preparata Research Articles

Investigate the effect of honey on the absorption of seven active ingredients from wu-tou decoction in rats.

Wu-tou decoction has been used as a traditional Chinese medicine prescription for thousands of years. It comprises five herbs, namely Radix Aconiti Preparata, Ephedrae Herba, Astragali Radix, Glycyrrhiza Radix, and Paeoniae Radix Alba. In addition, the original prescription contains honey, but in modern research, the existence of honey is commonly ignored. The aim was to investigate the effect of absorption in rats after oral wu-tou decoction with or without honey. In this research, a rapid and sensitive UPLC-MS/MS method was investigated for the quantitative analysis of ephedrine, pseudoephedrine, paeoniflorin, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, and benzoylmesaconine in rat plasma after single and continuous oral decoctions. The results of the pharmacokinetic parameters showed that Cmax , CL/F, AUC0-t , and AUC0-∞ in the honey group were significantly increased than those in the non-honey group except for ephedrine and pseudoephedrine. The same trend was observed regardless of single or continuous oral administrations. Research studies showed that honey could promote the absorption of some effective components in wu-tou decoction in rats, enhance bioavailability, and provide a theoretical basis for the scientific and rational compatibility of the original prescription.

Studies on the Incompatibility between Bulbus fritillariae and Radix aconiti praeparata Based on the P-gp.

Bulbus fritillariae and Radix aconiti praeparata are an incompatible herbal pair in the traditional Chinese medicine theory “eighteen incompatible medicaments,” and they should not be used simultaneously in clinical treatment for safety. This study aimed to investigate the incompatibility mechanism between Bulbus fritillariae and Radix aconiti praeparata based on their interaction with P-glycoprotein (P-gp). The interaction between Bulbus fritillariae and Radix aconiti praeparata during in vitro decocting as well as in vivo absorption was investigated by determining the dry extract yield and by rat single-pass intestinal perfusion (SPIP) model. Inhibition of different species of Bulbus fritillariae on P-gp function was examined using the SPIP model. The mRNA and protein expression of P-gp was determined by PCR and western blotting. The active ingredients of Bulbus fritillariae were predicted and screened for inhibiting P-gp activity by Schrodinger's molecular docking and MDR1-MDCK cell transport study, respectively. Mediation of monoester alkaloids in Radix aconiti praeparata by P-gp was predicted and examined using Schrodinger's molecular docking and SPIP experiment, respectively. In the results, when Radix aconiti praeparata was combined with Bulbus fritillariae, the toxic ingredient benzoylmesaconine in Radix aconiti praeparata displayed higher intestinal permeability, whereas the toxic ingredients showed no significant difference during the in vitro decoction process. Bulbus fritillariae thunbergii inhibited both the P-gp function and expression; in contrast, Bulbus fritillariae cirrhosae inhibited the function only. Alkaloids including peimine, peimisine, and imperialine were the active ingredients for inhibiting P-gp activity. Benzoylmesaconine in Radix aconiti praeparata was the substrate of P-gp.

Simultaneous Determination of Six Alkaloids in Rat Plasma by SPE-HPLC–MS/MS and Their Pharmacokinetics after Oral Administration ofRadix aconiti PreparataExtract

Simultaneous determination of the content of six alkaloids (aconitine, hypoaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, and benzoylmesaconine) in rat plasma is enabled by HPLC-MS/MS combined with microsolid phase extraction (micro-SPE). To study its pharmacokinetics in rat plasma, the extracted plasma sample was passed through a C18 extraction column and eluted with acetonitrile. The six alkaloids in the Radix aconiti Preparata extract can be completely separated as peaks with good shape. The six components in the plasma sample showed a good linear relationship within their respective linear ranges (R 2 > 0.997). The analysis of the six alkaloids can be completed within 20 min. This method has high intraday and interday precision, and the room temperature stability and freeze-thaw stability are good. The matrix effect of the plasma samples is between 86.4 and 114%. The metabolism of the six Aconitum alkaloids in plasma is analyzed using a two-compartment model, which is characterized by fast absorption, slow elimination, and good linear fit, R 2 > 0.99. The peak time (T max) for aconitine, hypaconitine, and neoaconitine ranged from 29.95 to 42.07 min, while the peak time (T max) for benzoaconitine, benzohypaconitine, and benzoxinaconitine ranged from 42.88 to 73.08 min. With the increased dosage, the bioavailability of Aconitum alkaloids decreased gradually. The method for the determination of Aconitum alkaloids in rat plasma by high performance liquid chromatography-tandem mass spectrometry is sensitive and accurate, which is suitable for rat plasma analysis. The results provide a scientific basis for metabolic study of Aconitum alkaloids in vivo, and pave the way for clinical use of Aconitum medicinal materials and extracts.

Moxibustion improves learning-memory ability by promoting cellular autophagy and regulating autophagy-related proteins in hippocampus and cerebral cortex in APP/PS1 transgenic Alzheimer's disease mice

To observe the effect of moxibustion of acupoints of the Governor Vessel on the levels of cellular autophagy, β amyloid protein (Aβ) immunoactivity, and expression of LC3-Ⅰ， LC3-Ⅱ， p62 and p-P70S6K proteins in the hippocampal tissue of APPswe/PS1de9 (APP/PS1) double-transgenic Alzheimer's disease (AD) mice, so as to reveal its underlying mechanisms in improving AD. APP/PS1 double-transgenic AD mice were randomly divided into AD model, moxibustion, autophagy-inducer (Rapamycin) and autophagy-inhibitor (3-MA)＋moxibustion groups (n＝10 in each group), and other 10 C57BL/6J male mice (the same age) were used as the normal control group. Herbal-cake (made of Chuanwu [Radix Aconiti Praeparata]) partitioned moxibustion was applied to "Baihui"(GV20), moxibustion was applied to "Fengfu"(GV16) and "Dazhui"(GV14), all for 20 min, once daily for 2 weeks, with one day's off between two weeks. For mice of the autophagy-inducer and 3-MA＋moxibustion groups, Rapamycin (2 mg•kg－1•d－1) and 3-MA (1.5 mg•kg－1•d－1) were separately administered by intraperitoneal injection for 2 weeks. The cognitive ability was examined by Morris water maze tests, and the ultrastructural changes (including autophagic lysosomes, etc.) of hippocampal neurons were observed by using transmission electron microscopy. The immunoactivity of cerebral cortex and hippocampal Amyloid β peptide 1-42 (Aβ1-42) was detected by immunohistochemistry, and the expression levels of hippocampal LC3-Ⅰ， LC3-Ⅱ， p62 and p-P70S6K proteins were detected by Western blot. After modeling, the escape latency of Morris water maze tasks was prolonged in the model group than in the normal control group (P<0.05) and obviously shortened in the moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.05). Results of transmission electron microscope showed deformed, irregular or atrophic neurons with rough and incomplete and fuzzy nuclear membrane, and decreased intracellular autophagosomes in the hippocampus in the model group, and partial irregular, atrophic neurons with more autophagic vesicles and lysosomes in the moxibustion group. The expression levels of Aβ1-42 in both cerebral cortex and hippocampus tissues, and LC3-Ⅰ， p62 and p-P70S6K proteins in the hippocampus were consi-derably up-regulated in the model group relevant to the normal control group (P<0.01), and evidently down-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01), while that of hippocampal LC3-Ⅱ protein and LC3-Ⅱ/Ⅰ ratio levels were obviously down-regulated in the model group relevant to the normal control group (P<0.01), and significantly up-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01)．. Moxibustion can improve the cognitive ability of APP/PS1 double-transgenic AD mice, which is associated with its effects in promoting hip-pocampal and cerebral cortex autophagy level, and down-regulating the expression levels of Aβ1-42, LC3-Ⅰ， p62 and p-P70S6K proteins in the hippocampus.

Textual research on a prescription, "Pill of Semen Plantaginis" in the Tangut medical documents unearthed in Khara-Khoto

A prescription, "Pill of Semen Plantaginisfor Treating All Diseases" (И(HB).N(O).4384) carried in the Tangut medical documents unearthed in Khara-Khoto was published in the 10(th)Volume of Heishuicheng Manuscript Collected in Russia. The prescription is composed of Herba Cistanches, Radix Achyranthis, Semen Plantaginis, white poria, Cortex Cinnamomi, Radix Aconiti preparata, Semen Cuscutaeand baked ginger, whose main function is invigorating kidney yang and nourishing kidney essence. This prescription has a close relationship with the Han prescription in central plain of China which may be based on certain lost Chinese medical book.

The anti-gastric ulcer effects of combined administration of Bletilla striata and Radix aconiti preparata in mice on the basis of uniform design

Objective To study the influence of the combined administration of Bletilla striata and Radix aconiti preparata with different doses or ratios on anhydrous ethanol-induced gastric mucosal injury in mice with gastric ulcer. Methods The uniform design method was adopted on the basis of two factors and seven levels, which aims to investigate the influence of combined oral administration of Bletilla striata and Radix aconiti preparata with different doses or ratios on gastric mucosal injury in the mice with gastric ulcer. The indices like gastric ulcer index and stomach mucosa damage index were used to help selecting the right dose or ratio of decoctions for further study. Results The combined administration of Bletilla striata and Radix aconiti preparata at a certain proportion could reduce gastric ulcer index and stomach mucosa damage index. According to the regression analysis, the gastric ulcer index and stomach mucosa damage index were obviously inhibited by Bletilla striata, while this function decreased with the combined administration of Bletilla striata and Radix aconiti preparata. However, an interactive effect between each other has not been found. The influence of decoctions on the gastric ulcer index and stomach mucosa damage index became less when the compatibility ratio of Radix aconiti preparata increased, which referred to the total dose ranged between 3.64 g/kg and 29.32 g/kg. Conclusions The effect of the combined administration of Bletilla striata and Radix aconiti preparata showed relationship among the doses and ratios on anhydrous ethanol-induced gastric mucosal injury in mice with gastric ulcer. Key words: Eighteen clashes; Radix aconiti preparata; Bletilla striata; Stomach ulcer; Mice

A study on the holistic efficacy of different Radix Aconiti Preparata for treating rheumatic arthritis in rats based on the urinary metabonomic method using UPLC-Q-TOF-HDMS

15 potential biomarkers related to the efficacy of RadixAconiti Preparatain adjuvant-induced arthritis rats had been identified by UPLC-Q-TOF-MS in urine, and they are mainly involved in four metabolic pathways.

Simultaneous Separation and Determination of Aconitine Compounds in &lt;i&gt;Radix aconiti praeparata&lt;/i&gt; by High Performance Capillary Zone Electrophoresis

A simple and inexpensive high performance capillary zone electrophoresis (CZE) was applied to separate and determine three alkaloids in Radix Aconiti Praeparata simultaneously. The optimized conditions for separation were obtained using 20 mmol/L borax buffer (pH 9.0) containing 2 mmol/L beta-cyclodextrin (β-CD) and 20% methanol. Online UV detection was performed at 235 nm. A voltage of 16 kV was carried at 25°C. Injection was performed at 0.5psi for 10 s. The separation and determination were satisfactory and quick.

Bioactivity fingerprint analysis of cyclooxygenase-2 ligands from radix Aconiti by ultrafiltration–UPLC–MSn

A novel fingerprinting method, bioactivity fingerprint analysis, based on an ultrafiltration-ultraperformance liquid chromatography-multistage tandem mass spectrometry (UPLC-MS(n)) method is proposed for the quality control of herbal medicines from the bioactivity viewpoint concerning the efficacy of herbal medicines. The bioactivity fingerprints reflecting the anti-inflammatory activities of radix Aconiti and radix Aconiti preparata were established. With use of ultrafiltration UPLC-MS(n), 11 cyclooxygenase-2 ligands from radix Aconiti preparata and 14 cyclooxygenase-2 ligands from radix Aconiti were found after incubation with cyclooxygenase-2. Twelve of the cyclooxygenase-2 ligands were identified by the ultraperformance UPLC-MS(n) method. The enrichment factor of each peak in the bioactivity fingerprint was calculated and was demonstrated to be characteristic, which makes bioactivity fingerprint analysis for the quality control of herbal medicines possible from the viewpoint of their bioactivities.

Rapid quality assessment of Radix Aconiti Preparata using direct analysis in real time mass spectrometry

This study presents a novel and rapid method to identify chemical markers for the quality control of Radix Aconiti Preparata, a world widely used traditional herbal medicine. In the method, the samples with a fast extraction procedure were analyzed using direct analysis in real time mass spectrometry (DART MS) combined with multivariate data analysis. At present, the quality assessment approach of Radix Aconiti Preparata was based on the two processing methods recorded in Chinese Pharmacopoeia for the purpose of reducing the toxicity of Radix Aconiti and ensuring its clinical therapeutic efficacy. In order to ensure the safety and effectivity in clinical use, the processing degree of Radix Aconiti should be well controlled and assessed. In the paper, hierarchical cluster analysis and principal component analysis were performed to evaluate the DART MS data of Radix Aconiti Preparata samples in different processing times. The results showed that the well processed Radix Aconiti Preparata, unqualified processed and the raw Radix Aconiti could be clustered reasonably corresponding to their constituents. The loading plot shows that the main chemical markers having the most influence on the discrimination amongst the qualified and unqualified samples were mainly some monoester diterpenoid aconitines and diester diterpenoid aconitines, i.e. benzoylmesaconine, hypaconitine, mesaconitine, neoline, benzoylhypaconine, benzoylaconine, fuziline, aconitine and 10-OH-mesaconitine. The established DART MS approach in combination with multivariate data analysis provides a very flexible and reliable method for quality assessment of toxic herbal medicine.

Research on Fuzi based on animal thermotropism behavior to discover if it has fewer “hot” characteristics without Ganjiang

ObjectiveTo investigate whether Fuzi (Radix Aconiti Praeparata) has fewer “hot” characteristics when administered without Ganjiang (Rhizoma Zingiberis). MethodsDifferences in the thermotropism behaviors of mice treated either with Fuzi (Radix Aconiti Praeparata), Ganjiang (Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System. The water intake volume, oxygen consumption volume, adenosine triphosphatase (ATPase) activity, total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activity were determined during the investigation. ResultsWhen Fuzi and Ganjiang were administered together, the rate at which mice remained on a warm plate (“remaining rate”) and the times and distances of their movement were all significantly reduced (P<0.05). Compared with the Normal group, the reduction was 55.1%, 48.3% and 44.8%, while compared with the Fuzi group, the reduction was 57.6%, 34.3% and 36.0%, indicating that “cold” tropism was significantly increased. Compared with the Normal and Fuzi groups, the ATPase activity and the respiratory oxygen consumption volume of the Fuzi + Ganjiang group were significantly increased (P<0.05), suggesting an improvement in energy metabolism and showing a “hot” characteristic when Fuzi and Ganjiang are present together. Additionally, the T-AOC and T-SOD activity were significantly enhanced (P<0.05). ConclusionThe behavior of mice tending toward “cold” tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent w ith a “hot” nature when not used with Ganjiang, the functional mechanism of which may be a change in the ATPase activity in liver tissue.

The comparative research on constituents of Radix Aconiti and its processing by HPLC quadrupole TOF‐MS

Based upon the regulations stipulated by the State Food and Drug Administration of China, only the processed, detoxified tubers and roots of Aconitum are allowed to be administered orally, used in clinical decoctions and adopted as raw materials for pharmaceutical manufacturing, so the processing principle of preparation of Radix Aconiti is important for ensuring the Radix Aconiti praeparata quality. A simple approach was described for HPLC-Q-TOF-MS screening and identification of many of the aconitine alkaloids present in unprocessed Radix Aconiti and Radix Aconiti praeparata. To compare their fingerprints, the processing principle of preparation of Radix Aconiti was developed. Twenty-nine compounds and 26 compounds were assigned to aconitine alkaloids and tentatively identified by comparing accurate mass and fragments information with that of the authentic standards or by mass spectrometry analysis and retrieving the reference literature. The nonester alkaloids were almost the same. The diester diterpene alkaloids were decreased, the monoester-diterpene alkaloids were increased and lipo-alkaloids decreased obviously in the processing of the preparation. These transformed components could be regarded as potential chemical markers that can be used to distinguish between raw and processed herbs.

Quantitative determination of total aconitines in commercial Aconitum L. Chinese medicine

Aconitines is predominant bioactive constituents in Aconitum L. Chinese medicines, which often cause serious toxicities problem in clinical application. This experiment evaluates the qualities of commercial Aconitum L. Chinese medicines by investigating the content of total aconitines. It was determined by the visible spectrophotometric method. The commercial 20 Radix Aconiti Lateralis Preparata, 26 Radix Aconiti Preparata and 20 Radix Aconiti Kusnezoffii Preparata, the total content of aconitines ranges from 0.017 to 2.81%, 0.278 to 1.303%, and from 0.0066 to 1.526%, respectively. The results showed that the total content of aconitines in Aconitum L. Chinese medicines were obviously different, this may pose serious problem in clinical applications. Key words: Aconitum L. Chinese medicines, total alkaloids, visible spectrophotometry method, aconitine.

Analysis of Chinese medicine preparations by capillary electrophoresis–mass spectrometry

In Chinese medicines, herbs are usually prepared before use by patients. Since the preparation procedures convert the original component into one or more products, study of the procedures is usually complex and involves several compounds. On-line coupling of capillary electrophoresis (CE) to mass spectrometry (MS) allows both the efficient separation of CE and the specific and sensitive detection of MS to be achieved. In this study, CE–MS was applied to the determination of alkaloids in Maqianzi (the seed of Strychnos pierrian) and Wutou (aconite root, Radix aconiti praeparata) during the preparation procedure. With optimal CE–MS conditions, alkaloids in both prepared and unprepared Maqianzi were determined successfully in the total ion current (TIC) mode. However, single ion monitoring (SIM) had to be applied for the separation of aconitum alkaloids and their hydrolysis products. Quantification data indicated that MS detection under SIM mode is more sensitive than UV detection. Based on the CE–MS method developed, the hydrolysis of aconitum alkaloids in water and methanol was also studied.

Study of the mechanisms of acupuncture and moxibustion treatment for ulcerative colitis rats in view of the gene expression of cytokines.

AIM:To observe the effect of acupuncture and moxibustion on the expression of IL-1beta and IL-6 mRNA in ulcerative colitis rats.METHODS:The SD rat ulcerative colitis model was created by immunological method associated with local stimulation. Colonic mucosa was prepared from human fresh surgical colonic specimens, homogenized by adding appropriate amount of normal saline and centrifuged at 3000r/min. The supernatant was collected for measurement of protein conentration and then mixed with Freund adjuvant. This antigen fluid was first injected into the plantae of the model group rats, and then into their plantae, dorsa, inguina and abdominal cavities (noFreund adjuvant for the last injection) again on the 10th, 17th, 24th and 31st day. When a certain titer of serum anti colonic antibody was reached, 2% formalin and antigen fluid (no Freund adjuvant) were administered separately by enema. The ulcerative colitis rat model was thus set up. The animals were randomly divided into four groups: model control group (MC, n = 8), electro acupuncture group (EA, n = 8), herbs partition moxibustion group (HPM 8), normal control group (NC,n = 8). HPM: Moxa cones made of refined mugwort floss were placed on the medicinal pad (medicinal pad dispensing: Radix Aconiti praeparata, cortex Cinnamomi, etc) for Qihai (RN 6) and Tianshu (ST 25, bilateral) and ignited. Two moxa cones were used for each acupoint once a day and 14 times in all. EA: Tianshu (bilateral) and Qihai were stimulated by the intermittent pulse with 2Hz frequency, 4mA intensity for 20 minutes once a day and 14 times in all. After treatment, rats of all four groups were killed simultaneously. The spleen was separated and the distal colon was dissected. Total tissue RNA was isolated by the guanidinium thiocyanate phenol chloroform extraction method. RT-PCR technique was used to study the expression of IL-1 beta and IL-6 mRNA.RESULTS:IL-1 beta and IL-6 mRNAs were not detected in the spleen and colonic mucosa of the NC rats, whereas they were significantly expressed in that of the MC rats.IL-1 beta and IL-6 mRNAs were markedly lower in the EA and HPM rats than that in MC rats. There was no significant difference between the levels of IL-1 beta and IL-6 mRNAs in the EA and HPM rats. The expressions of IL-1 beta and IL-6 mRNAs were nearly the same in the spleen and colon of all groups.CONCLUSION:Acupuncture and moxibustion greatly inhibited the expression of IL-1 beta and IL-6 mRNA in the experimental ulcerative colitis rats.