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 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 investigate the difference of hypaconitine concentration in serum between normal and cold-deficiency mice after administration of aconite decoction. To analyze how the toxic dose of aconite decoction correlate to the metabolic environment.

METHODPrepared cold-deficiency mice model, treated normal and cold-deficiency mice with aconite decoction for 14 days continuously, and then detected hypaconitine concentration in serum by HPLC along with survival ratio of mice on the first, seventh and fourteenth day.

RESULTAfter administration of aconite decoction for 14 days, the hypaconitine concentration in serum of cold-deficiency mice is close to that in normal mice. It showed aconite decoction has the ability of regulating metabolism environment, the hypaconitine concentration in serum of normal mice was higher on the seventh and fourteenth day than that on first day. It showed that aconite decoction can disturb metabolism environment of normal mice. It was also been observed that the range of variation of hypaconitine concentration in cold-deficiency mice was minor than that in normal mice during the fourteen days' administration.

CONCLUSIONThe difference of serum concentration in normal and cold-deficiency mice showed that there were different metabolic environments in two mice models, and the metabolic environment changed during administration. These results showed that the different toxic doses of aconite decoction were partially due to the different metabolic environments.

Aconitine ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Aconitum ; chemistry ; Animals ; Cold Temperature ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Male ; Mice ; blood ; physiology ; Mice, Inbred ICR

OBJECTIVETo investigate the mechanism of action on compatible using of total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba therapy on rheumatoid arthritis in rats.

METHODThe rat models of rheumatoid arthritis of cold and dampness syndrome were treated with total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba. Observed the contents of hypothalamic L-ENK, hypothalamic-END, plasmatic SP, serumal IgG, serumal cell factors (IL-1beta, TNF-alpha, IL-6, IL-2, IL-10) by radioimmunity method and ultrastructural change of synovial cell in electron microscope.

RESULTTotal alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba could relieve arthrocele and arthralgia and elevate the contents of L-ENK, beta-END, IL-2 and degrade the contents of SP, IgG, IL-1beta, IL-6 and inhibit abnormal secretion accentuation of synovial cell like fiber.

CONCLUSIONTotal alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba could be used to treat rheumatoid arthritis of cold and dampness syndrome. The mechanism of action might be that the contents of center endogenous opioid peptides had increased, the synthesis and release of SP had been inhibited, the disturbance of serumal cell factor had been adjusted, and the synthesis and secretion of serum immune globulin and abnormal secretion accentuation of synovial cell had been inhibited.

Aconitum ; chemistry ; Alkaloids ; administration & dosage ; Animals ; Arthritis, Rheumatoid ; drug therapy ; genetics ; immunology ; Cytokines ; genetics ; immunology ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Glycosides ; administration & dosage ; Humans ; Male ; Paeonia ; chemistry ; Polysaccharides ; administration & dosage ; Rats ; Rats, Sprague-Dawley

AIMTo develop an HPLC method for the determination of Aconitum alkaloids extracted from Radix aconiti preparata in rats.

METHODSWaters 2690@996 PAD system was used. The analytical column was a Halsil 100 C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase was water, methanol and diethyl amine at the ratio of 75:25:0.1. The flow rate was 0.9 mL.min(-1). The wavelength of the detector was 240 nm.

RESULTSThe linear ranges of aconitine in the heart, spleen, lung and kidney were 0.4-100 microg.mL(-1), the correlation coefficients were 0.9972, 0.9986, 0.9993 and 0.9994, respectively. The linear range of aconitine in liver was 2-200 microg.mL(-1) and the correlation coefficient was 0.9990. The linear ranges of hypaconitine in heart, liver, spleen, lung, kidney, brain and spinal cord were 5-100 microg.mL(-1), the correlation coefficients were 0.9994, 0.9997, 0.9998, 0.9984, 0.9998, 0.9998 and 0.9997, respectively. Detection limits (S/N = 3) of aconitine and hypaconitine were 0.4 microg.mL(-1). The recoveries of aconitine and hypaconitine ranged from 88.7% to 102.2% and 86.5% to 101.3%, respectively, and the RSD of precision of aconitine and hypaconitine was 10%.

CONCLUSIONIt appears to be an accurate and effective method that can offer reference basis for in toxication of Radix aconiti preparata clinically.

Aconitine ; analogs & derivatives ; metabolism ; Aconitum ; chemistry ; Administration, Oral ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Myocardium ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Spleen ; metabolism ; Tissue Distribution

OBJECTIVETo study the transdermal osmosis process of Aconitum brachypodum's liniment, gel and patcher to provide basis for selecting dosage form and controlling the quality.

METHODTaking the cumulate rate of transdermal as index, a imitated Fick's diffusion device was used for the investigating the transdermal osmosis course of the three preparations. The best transdermal mathematics models are obtained and the relations between the transdermal course and the release course are analysed.

RESULTThe three preparations have different characteristics of transdermal osmosis course. The liniment meets dynamics 0 order process, the gel and the patcher meet dynamic 0 order process of non-corroded drug system. And the relation is good cubic equation between their transdermal course and release course.

CONCLUSIONThe transdermal osmosis experiment in vitro for three preparations can provide basis for selecting dosage form and the quality control in future studies.

Aconitum ; chemistry ; Administration, Cutaneous ; Animals ; Diffusion ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; In Vitro Techniques ; Male ; Osmosis ; Plant Tubers ; chemistry ; Plants, Medicinal ; chemistry ; Rabbits ; Skin ; metabolism ; Skin Absorption

Aconite is a common remedy of herb doctors and is widely used in the Far East. Clinical aspects of the visual disturbance produced by this drug have been described, but little is known about its pathology. Tinctura aconiti (0.6 mg of total alkaloid/kg 2x) was administered intraperitoneally in rabbits to evaluate its toxic effects on the visual system. The alteration in the visual evoked potential following aconite injection consisted of a delay in the onset and peak latency. Histopathologically, there were damages to the myelin sheath of the visual pathway, spinal cord and peripheral nerves. These findings suggest that aconite may cause primarily myelo-optic neuropathy.
Aconitum/administration & dosage/*toxicity ; Animals ; Evoked Potentials, Visual/*drug effects ; Injections, Intraperitoneal ; Myelin Sheath/*drug effects/ultrastructure ; Optic Nerve/*drug effects/ultrastructure ; Optic Nerve Diseases/*chemically induced/pathology ; Rabbits ; Spinal Cord/*drug effects/ultrastructure

OBJECTIVEThrough the paired comparison on the toxicity effect of Aconiti Lateralis Radix Praeparata of different compatibility proportion of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma, to observe the detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata.

METHODPaired comparison on the mouse acute toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the LD50. Paired comparison on the rat heart toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the TD50. We dilute medicated serum of Aconiti Lateralis Radix Praeparata, Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (3:1), Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (1: 1) into 5%, 10%, 20% solution with serum free DMEM, to survey the effect of different concentration of medicated serum to the pulsing rhythm of myocardial cell of original generation newborn rat, cell surviva rate and content of LDH in myocardial cells.

RESULTLD50 and TD50 of Aconiti Lateralis Radix Praeparata can be increased after adding Glycyrrhizae Radix et Rhizoma Compared to the blank serum, medicated serum with Aconiti Lateralis Radix Praeparata can obviously increased the pulse rhythm of myocardial cell and the content of LDH (P < 0.05). The medicated serum with Aconiti Lateralis Radix Praeparata added different proportion of Glycyrrhizae Radix et Rhizoma can reduce the acceleration of myocardial cell's rhythm, which is induced by Aconiti Lateralis Radix Praeparata, and can reduce the content of LDH. With the increased ratio of Glycyrrhizae Radix et Rhizoma, the effect is stronger. But for the serum with different concerntration of Aconiti Lateralis Radix Praeparata or Aconiti Lateralis Radix Praeparata added Glycyrrhizae Radix et Rhizoma, there is no obvious effect to the cell survival.

CONCLUSIONGlycyrrhizae Radix et Rhizoma has the detoxication effect through increasing the ultimatetotaldosage of Aconiti Lateralis Radix Praeparata. The detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata is through restraining the increased rhythm of myocardial cell and protecting the myocardial cell.

Aconitum ; chemistry ; Animals ; Cells, Cultured ; Chemistry, Pharmaceutical ; methods ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; toxicity ; Female ; Glycyrrhiza ; chemistry ; Inactivation, Metabolic ; Male ; Mice ; Mice, Inbred ICR ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry

The primary objective was to develope a UPLC method for determine the concentration of buspirone hydroxychloride in plasma and to evaluate the effects of Aconiti Laterlis Radix and Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix on CYP3A4 in vivo. ACQUITY UPLC BEH C18 column (2.1 mm x 10 mm, 1.7 microm) was used for the gradient elution with a 2.0 mmol x L(-1) ammonium acetate (pH 7.4, A)-acetonitrile (B) solution, 0-2.2 min, 10% - 60% B, 2.2-2.5 min, 60% B, 2.5-3.0 min, 60%-75% B, 3.0-3.5 min, 75% B, 3.5-4.0 min, 75%-10% B, at the flow rate of 0.3 mL x min(-1) at room temperature. The UV wavelenght was detected at 243 nm. The linear calibration curve ranged between 0.078 125-20.0 microg (r = 0.9975). The average recovery (n = 6) of buspirone hydroxychloride was 85.62% (RSD 6.8%). The results showed that this method has good specificity and repeatability, and which can be used for the determination of buspirone hydrochlorid in serum. In animial studies, single dose Aconiti Laterlis Radix extract treatment (0.5 g x kg(-1)) decreased buspirone hydroxychloride AUC(0-2 h) (52.8%, P = 0.020), increased CL/F (122%, P = 0.045). Compared to the saline treatment group, Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract treatment has no effect on CYP3A4 in rat. The results indicated that Aconiti Laterlis Radix extract induced CYP3A4 while Aconiti Laterlis Radix compatibility of Glycyrrhizae Radix extract had no effect on CYP3A4 in vivo. Aconiti Laterlis Radix had been detoxified when be used as compatibility of Glycyrrhizae Radix.
Aconitum ; chemistry ; Animals ; Chromatography, High Pressure Liquid ; methods ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression ; drug effects ; Glycyrrhiza ; chemistry ; Herb-Drug Interactions ; Male ; Rats ; Rats, Sprague-Dawley