Aconitum heterophyllum (Patrees) is a critically endangered medicinal herb of the northwestern Himalayas and has enormous pharmacological potential. It is the only nonpoisonous member of the genus Aconitum, and has been used as a medicinal herb since ancient times. A. heterophyllum is an important ingredient in many traditional systems of medicine. Mostly, it is harvested for its roots, and its medicinal properties are due to the presence of diverse bioactive secondary metabolites, commonly known as aconites. Our understanding of the pharmacological properties of this intriguing genus is continuously growing due to its broad chemical diversity. The therapeutic uses identified by traditional medicinal practice are receiving extensive study. Multiple in vitro experimental investigations of A. heterophyllum have reported the analgesic, anti-inflammatory, antiarrhythmic, antiparasitic and anticancer properties, as well as its effects on the central nervous system. In this review, we highlight the classification, distribution, commerce, traditional uses, phytochemistry, pharmacology and conservation measures relevant to this species. Additionally, this review includes the biosynthetic pathways of A. heterophyllum's key constituents, which could be targeted to enhance the expression levels of desired metabolites via genetic interventions. Studying the genomics, transcriptomics, proteomics and metabolomic aspects of this species would be helpful in developing highly designed genotypes and chemotypes of this species to be used in commercial production.
Aconitum/genetics* ; Ethnopharmacology ; Plant Extracts/chemistry* ; Plant Roots/chemistry* ; Plants, Medicinal/chemistry*

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.
Aconitum ; Gene Expression Profiling ; Genes, Plant/genetics* ; Real-Time Polymerase Chain Reaction ; Reference Standards ; Reverse Transcriptase Polymerase Chain Reaction

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

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 influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique.

METHODThe asthenia cold syndrome rat models were established by administering traditional Chinese medicine raw Gypsum Fibrosum, Gentianae Radix, Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma. After treated with Aconiti Lateralis Radix Praeparata, the rats' liver gene expressions were detected using gene chip. Differential expression genes were screened for gene function annotation, and some genes were selected to check the accuracy of the results by RT-PCR.

RESULTCompared with the asthenia cold model group, the asthenia cold treatment group showed 212 differential expression genes, mainly involving function of immune response and oxidoreductase activity.

CONCLUSIONAconiti Lateralis Radix Praeparata is proved to have an effect on up-regulating immune response-related genes and oxidizing oxidoreductase activity-related genes of asthenia cold syndrome rats and may be a molecular mechanism for classical warm-nature medicine Aconiti Lateralis Radix Praeparata in warming meridians and dissipating cold.

Aconitum ; chemistry ; Animals ; Asthenia ; drug therapy ; genetics ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Profiling ; Genomics ; Liver ; drug effects ; metabolism ; Male ; Oligonucleotide Array Sequence Analysis ; Rats ; Rats, Wistar

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

OBJECTIVETo investigate the regulation of Cha Gan Beng Ga on the activity of biomarker PGC-1α in vivo and in vitro, and lay the foundation for studying the efficacy result of Cha Gan Beng Ga on xenograft tumor model and extracting active constituents.

METHOD(1) The coarse powder of Cha Gan Beng Ga was extracted with 70% ethanol solution through heating and refluxing, and finally was used to freeze dry powder. (2) 50 mg x kg(-1) of freeze-dried power was orally administrated to KM and C57BL/6J mice once daily, lasting for 5 consecutive days; different concentrations of extracted materials was given to non-small cell lung cells A549. (3) The expression level of PGC-1α mRNA was quantitatively determined in lung tissue of mice and non-small cell lung cells A549.

RESULTThe expression levels of PGC-1α in lung tissue of different mice strains had an increasing tendency. Furthermore, the expression levels of PGC-1α in non-small cell lung cells A549 also had an increasing tendency, showing dose and time-dependent relationships.

CONCLUSIONMongolian Medicine Cha Gan Beng Ga could induce the over-expression of PGC-1α mRNA in lung tissue of mice and in non-small cell lung cells A549. The present results will lay foundation for studying the efficacy result of antitumor and active constitutes in future.

Aconitum ; chemistry ; Animals ; Biomarkers, Tumor ; genetics ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Lung ; drug effects ; metabolism ; Lung Neoplasms ; genetics ; pathology ; Male ; Medicine, Mongolian Traditional ; Mice, Inbred C57BL ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Plant Extracts ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Transcription Factors ; genetics

OBJECTIVETo investigate the effect of shenfu injection on canine with cardiogenic shock and the possible mechanism.

METHODCardiogenic shock model of canine was established by ligating left anterior descending (LAD) of coronary artery. The 15 canines with cardiogenic shock were randomly divided in to glucose injection group, shenfu injection group and sham-operated group. The hemodynamics parameters were monitored. Plasma TNF-alpha and IL-1beta levels were measured by radioimmunoassay. Expression of TNF-alpha mRNA and IL-1beta mRNA in myocardium were detected by RT-PCR.

RESULTFollowing cardiogenic shock, the mean artery pressure (MAP), left ventricular systolic pressure (LVSP), ventricular pressure rise ratio during systolic period (+ dp/dt(max)), and ventricular pressure decay ratio during diastolic period (- dp/dt(max)) decreased significantly; the plasma TNF-alpha and IL-1beta levels and the expression of TNF-a mRNA and IL-1beta mRNA in myocardium increased significantly. In shenfu injection group, MAP, LVSP and +/- dp/dt(max) increased significantly and plasma TNF-alpha and IL-1beta levels decreased significantly. In glucose injection group, MAP, LVSP, +/- dp/dt(max) and plasma TNF-alpha and IL-1beta levels had not changed significantly. The expression of TNF-alpha mRNA and IL-1beta mRNA in myocardium were significantly lower in shenfu injection group than those in glucose injection group.

CONCLUSIONShenfu injection probably can decrease over-exprssion of TNF-alpha mRNA and IL-1beta mRNA on transcription platform. Shenfu injection counteract cardiogenic shock, relieve myocardium damage and improve hemodynamics through inhibiting overproduction of TNF-alpha and IL-1beta.

Aconitum ; chemistry ; Animals ; Cytokines ; biosynthesis ; blood ; genetics ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; Hemodynamics ; drug effects ; physiology ; Injections, Intravenous ; Interleukin-1beta ; biosynthesis ; blood ; genetics ; Male ; Myocardium ; metabolism ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Shock, Cardiogenic ; physiopathology ; prevention & control ; Tumor Necrosis Factor-alpha ; biosynthesis ; blood ; genetics

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 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