Veratrum alkaloids in Veratrum maackii may cause significant gastrointestinal symptoms, bradycardia, hypotension, and arrythmia. We experienced successful outcomes in two patients who were victims of poisoning due to ingestion of Veratrum maackii, which was mistaken for Allium victorialis var. platyphyllum. One patient developed hypotension and prolongation of QT interval in electronicardiogram (ECG) and was treated with administration of vasopressor and magnesium. The other patient developed bradycardia and was treated with administration of atropine. Both patients were kept under close observation, and received supportive care, and both patients were discharged without any symptoms or complications.
Allium ; Arrhythmias, Cardiac ; Atropine ; Bradycardia ; Eating ; Humans ; Hypotension ; Magnesium ; Veratrum ; Veratrum Alkaloids

Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1～A-69), veratramine type(B-1～B-21), jervanine type(C-1～C-31), solanidine type(D-1～D-10) and verazine type(E-1～E-53), respectively, have been isolated and identified in the genus Veratrum. Their pharmacological activities mainly focused on decreasing blood pressure, anti-platelet aggregation and anti-thrombosis, anti-inflammatory and analgesic, and antitumor effect. This paper classified and summarized the 184 kind of steroidal alkaloids from the Veratrum plants and their major pharmalogical activities in order to provide the scientific basis for the further development and utilization of active alkaloids.
Alkaloids/pharmacology* ; Analgesics ; Platelet Aggregation ; Steroids/pharmacology* ; Veratrum

OBJECTIVETo study the steroidal alkaloids in Veratrum dahuricum.

METHODThe compounds were isolated and purified by various column chromatographic methods. Their structures were identified by spectroscopic analysis.

RESULTFive compounds were isolated and identified as (20R, 22S, 25S)-veratra-5,13-dien-3beta-ol (1), angeloylzygadenine (2), 15-O-(2-methylbutanoyl)-3-O-veatroylprotoverine (3), 20-isoveratramine (4), veratramine (5).

CONCLUSIONCompound 1 was a new compound, compounds 24 were obtained from the plant for the first time.

Alkaloids ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Isomerism ; Steroids ; chemistry ; Veratrum ; chemistry

OBJECTIVETo observe the role of the Hedgehog (Hh) genes in the proliferation of osteoblasts upon mechanical tensile strains.

METHODSPrimary osteoblasts harvested from newborn rat calvarial bone were subjected to 3% and 6% elongation of tensile stretches using Flexcell 4000 strain unit. The cultures were also treated with either recombinant N-terminals Sonic Hedgehog (N-Shh) or cyclopamine (cy), a Hh inhibitor or gadolinium (GdCl3), an inhibitor of stretch-activated channels. The proliferation of osteoblasts was quantified by cell counting, methyl thiazolyl tetrazolium (MTT) and cell cycle detection via flow cytometry. Statistical analysis was performed using SAS 8.0 software package.

RESULTSThe tensile strain, especially under 6% elongation, promoted osteoblast proliferation. Stretching force could also promote the proliferation even when the cells were treated with cy, but this effect was suppressed by GdCl3.

CONCLUSIONThe induced proliferation of osteoblasts by mechanical stretched is mediated at least in part by Indian Hedgehog (Ihh) signaling.

Animals ; Cell Proliferation ; Hedgehog Proteins ; Osteoblasts ; Rats ; Signal Transduction ; Veratrum Alkaloids

OBJECTIVE: To study the effect of SMO inhibitor (Jervine) on proliferation, apoptosis and cell cycle of MDS cell line MUTZ-1, and its mechanism. METHODS: The effect of different concentrations Jervine on proliferation of MUTZ-1 cells was detected by CCK-8 method. Apoptosis and cell cycle of MUTZ-1 cells were detected by flow cytometry. Western blot was used to detect the changes of Shh signaling pathway effecting proteins BCL2 and CyclinD1. The expression levels of Smo and Gli1 gene were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: Jervine inhibited MUTZ-1 cell proliferation in a concentration dependent manner (24 h, r=-0.977), the apoptosis rate of MUTZ-1 cells increased with the enhancement of concentration of Jervine in MUTZ-1 cells (P＜0.001), the cell proportion of G phase increased and the cell number of S phase decreased with enhancement of concentration (P＜0.001). The result of RT-qPCR and Western blot showed that the expression of Smo, Gli1 mRNA and BCL2, CyclinD1 proteins decreased (P＜0.05). CONCLUSION SMO inhibitor can effectively inhibit the growth of MDS cell line MUTZ-1 improve the cell apoptosis and induce cell cycle arrest. Its action mechanism may be related with dowm-regulating the expression of BCL2 and CyclinD1.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Hedgehog Proteins ; Humans ; Myelodysplastic Syndromes ; Signal Transduction ; Veratrum Alkaloids

OBJECTIVETo develop an HPLC-ELSD method for determination of vetatramine. in Veratrum nigrum.

METHODThe analy fical column was Shim-pack ODS - C18 (4.6 mm x 250 mm, 4 microm) column, the mobile phase was acetonitrile-water (containing 0.1% triethylamine) (50:50), at a flow rate of 0.8 mL x min(-1). The temperature of drift tube was 90 degrees C and the gas flow was at the rate of 2.5 L x min(-1).

RESULTThe calibration curve was linear in the range of 0.36-3.6 microg (r = 0.999 8). The average recovery was 100.9% (RSD 2.3%, n = 6). The contents of veratramine in Veratrum nigrum. from the ten different sources were determined.

CONCLUSIONThe method may be used as a accurate and reproducible way to determine the content of veratramine in V. nigrum.

Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Linear Models ; Reproducibility of Results ; Sensitivity and Specificity ; Veratrum ; chemistry ; Veratrum Alkaloids ; analysis ; isolation & purification

Veratrum patulum is a perennial plant with toxicity, which grows wild in the high mountain areas of Korea. Various types of steroidal alkaloids contained in Veratrum patulum are known to cause symptoms such as nausea, vomiting, bradycardia and hypotension. Twenty-three patients were admitted to our center with chief complaints of nausea and vomiting after ingesting leaves of Veratrum patulum. The mean age of the group was 44 years old and was comprised of 19 males and 4 females. Some patients showed hypotension and bradycardia with symptoms such as dizziness. Ten patients with severe bradycardia coupled with other symptoms received atropine administration. Nausea and vomiting were improved after the administration of anti-emetics. Blood pressure and the pulse rate were all normalized on the day after admission, and all of the patients were discharged without any symptoms.
Alkaloids ; Antiemetics ; Atropine ; Blood Pressure ; Bradycardia ; Dizziness ; Female ; Heart Rate ; Humans ; Hypotension ; Korea ; Male ; Nausea ; Plants ; Veratrum ; Vomiting

A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.
Chemistry Techniques, Synthetic ; methods ; Molecular Structure ; Organic Chemistry Phenomena ; Stereoisomerism ; Steroids ; chemistry ; Veratrum Alkaloids ; chemical synthesis ; chemistry

PURPOSE: Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition (EMT) are both known to relate to cancer progression. The purpose of this study was to investigate the role of Shh signaling and EMT in renal cell carcinoma (RCC). MATERIALS AND METHODS: Cell proliferation was assayed in RCC cell lines in the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh) protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin. The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy specimens from RCC patients was also measured by immunohistochemical (IHC) staining. RESULTS: RCC cells showed enhanced cell proliferation by r-Shh protein, whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin and that this suppression was partly blocked by cyclopamine alone in RenCa cells. In the IHC results, osteonectin significantly correlated with vein sinus invasion (p=0.0218), and the expression of vimentin significantly correlated with lymphatic invasion (p=0.0392). CONCLUSIONS: Shh signaling and EMT play roles in RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible molecular targeted therapeutic strategy for RCC.
Cadherins ; Carcinoma, Renal Cell ; Cell Line ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Hedgehogs ; Humans ; Nephrectomy ; Osteonectin ; Polymethacrylic Acids ; Veins ; Veratrum Alkaloids ; Vimentin

OBJECTIVETo investigate the inhibitory effect of the Hedgehog signal pathway blocker (cyclopamine) on DU145 cells.

METHODSWe interfered DU145 cells with cyclopamine at the concentrations of 1, 10, 50 and 100 micromol/L and detected its inhibitory effect on the cells by MTT colorimetry assay at 24, 48 and 72 hours, as well as its effect on the cell cycle by flow cytometry. We also determined the difference in the mRNA expression of cyclin E between the experimental and control groups by RT-PCR at 48 hours after 50 +/- micromol/L cyclopamine intervention.

RESULTSCyclopamine inhibited the DU145 cells in a time- and dose-dependent manner, with inhibition rates of 7.42, 12.70 and 59.15% in the 10, 50 and 100 micromol/L groups respectively at 24 hours, significantly different from that of the blank control group (P < 0.05). It markedly suppressed the proliferation of the DU145 cells at >10 micromol/L at 24 hours. Flow cytometry showed an obviously increased proportion of stage G1 cells at the concentration of >10 micromol/L after 48-hour intervention, with statistically significant differences from the G1 cell proportions in the control, 10 micromol/L and 50 micromol/ L groups, which were (52.17 +/- 2.21)%, (60.13 +/- 2.75)% and (74.30 +/- 3.52)% respectively (P < 0.01). The apoptotic peak was elevated with the increased concentration of cyclopamine. The cyclin E mRNA expression of the DU145 cells was decreased by 61.90% at 48 hours after 50 micromol/L cyclopamine intervention as compared with the blank control group (P < 0.01).

CONCLUSIONCyclopamine can inhibit the proliferation of DU145 cells, and the mechanism may be related with its effect of down-regulating the cyclin E mRNA expression of DU145 cells and blocking them in stage G1. Cyclopamine can also induce the apoptosis of DU145 cells.

Apoptosis ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin E ; metabolism ; Down-Regulation ; Flow Cytometry ; Humans ; Male ; Signal Transduction ; drug effects ; Veratrum Alkaloids ; pharmacology