Advances in studies on steroidal alkaloids and their pharmacological activities in genus Veratrum / 中国中药杂志

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.

Resveratrol: Twenty Years of Growth, Development and Controversy

Resveratrol was first isolated in 1939 by Takaoka from Veratrum grandiflorum O. Loes. Following this discovery, sporadic descriptive reports appeared in the literature. However, spurred by our seminal paper published nearly 60 years later, resveratrol became a household word and the subject of extensive investigation. Now, in addition to appearing in over 20,000 research papers, resveratrol has inspired monographs, conferences, symposia, patents, chemical derivatives, etc. In addition, dietary supplements are marketed under various tradenames. Once resveratrol was brought to the limelight, early research tended to focus on pharmacological activities related to the cardiovascular system, inflammation, and cancer but, over the years, the horizon greatly expanded. Around 130 human clinical trials have been (or are being) conducted with varying results. This may be due to factors such as disparate doses (ca. 5 to 5,000 mg/day) and variable experimental settings. Further, molecular targets are numerous and a dominant mechanism is elusive or nonexistent. In this context, the compound is overtly promiscuous. Nonetheless, since the safety profile is pristine, and use as a dietary supplement is prevalent, these features are not viewed as detrimental. Given the ongoing history of resveratrol, it is reasonable to advocate for additional development and further clinical investigation. Topical preparations seem especially promising, as do conditions that can respond to anti-inflammatory action and/or direct exposure, such as colon cancer prevention. Although the ultimate fate of resveratrol remains an open question, thus far, the compound has inspired innovative scientific concepts and enhanced public awareness of preventative health care.

A new aurone glycoside from Veratrum dahuricum (Turcz.) Loes. f / 药学学报

To study the chemical constituents of Veratrum dahuricum (Turcz.) Loes. f., a new aurone glycoside named as (Z)-7, 4'-dimethoxy-6-hydroxyl-aurone-4-O-β-glucopyranoside was isolated from the 95% ethanol extracts of the rhizomes and roots of Veratrum dahuricum (Turcz.) Loes. f. by repeated column chromatography on silica gel and recrystallization. Its structure was established by extensive spectroscopic analyses, and its cytotoxicities against HepG-2, MCF7 and A549 cell lines were measured in vitro.

A Patient Presenting with Elevations of Cardiac Enzyme Levels after Veratrum Oxysepalum Ingestion

Veratrum patulum has toxicological relevance because of the potential for misidentification of this plant as mountain garlic. Veratrum patulum has an ester-alkaloid that provokes cardiac arrhythmias by excessive vagal stimulation and depression of the sinoatrial and atrioventricular nodes of the heart and hypotension, cardiomegaly. We report on a retrospective case of successful outcome in patients with veratrum patulum poisoning through active treatment from the early phase after ingestion. We report on a case involving a patient who experienced dizziness, dyspnea, hypotension, and elevation of cardiac enzyme, cardiomegaly. These cases were kept under observation and generally recovered with supportive care. We report on cases of veratrum patulum poisoning with review of literature.

Prosapogenin A inhibits cell growth of MCF7 via downregulating STAT3 and glycometabolism-related gene / 药学学报

This study is to investigate the inhibitory effect and mechanism of prosapogenin A (PSA) on MCF7. MTT assay was performed to determine the inhibitory effect of PSA on MCF7 cells. PI/Hoechst 33342 double staining was used to detect cell apoptosis. RT-PCR was used to test the mRNA levels of STAT3, GLUT1, HK and PFKL. Western blotting was performed to determine the expression of STAT3 and pSTAT3 protein in MCF7 cells. The results showed that PSA could dose-dependently inhibit cell growth of MCF7 followed by IC50 of 9.65 micrmol x L(-1) and promote cell apoptosis of MCF7. Reduced mRNA levels of STAT3, HK and PFKL were observed in MCF7 cells treated with 5 micromol x L(-1) of PSA. PSA also decreased the level of pSTAT3 protein. STAT3 siRNA caused decrease of mRNA of GLUT1, HK and PFKL which indicated STAT3 could regulate the expressions of GLUT1, HK and PFKL. The results suggested that PSA could inhibit cell growth and promote cell apoptosis of MCF7 via inhibition of STAT3 and glycometabolism-related gene.

Study on toxicity of uniform design-based compatible use of Veratrum nigrum and asarum / 中国中药杂志

The compatible use of Veratrum nigrum with asarum, is one of the eighteen incompatible pairs. To research the toxic regularity of the compatible use of V. nigrum and asarum, this experiment adopted the uniform design combining with acute toxicity test, with the number of died animals as the observation indicator. The results showed that the toxicity came from the common effect of V. nigrum and asarum, and V. nigrum after the compatible use, and V. nigrum made a greater contribution to the toxicity caused by the compatible use. But the toxicity did not absolutely enhance with the increase in use of V. nigrum.

Two Cases of Poisoning with Veratrum Maackii

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.

Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling / 癌症

The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1(neo/neo) and K14cre:SmoM2(YFP)). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis.

Modulation of activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Sophora flaveacens and coadministration with Veratrum nigrum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the modulatory effect of Sophora flaveacens and co-administration with Veratrum nigrum on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver.</p><p><b>METHOD</b>Rat liver microsomal cytochrome P450, b5, aminopyrine N-demethylase (APND), p-nitrophenol-hydroxylase (pNPH) activities were quantitated by UV chromatography. The mRNA expression level of five CYP isoenzymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULT</b>S. flaveacen and its combination with V. nigrum can dramatically reduce P450 and b5 protein content. Both single and combined use inhibited the activities of aminopyrine N-demethylase. At the mRNA level, the expression of CYP2C11 markedly induced exposure to V. nigrum, while decreased after combination with S. flaveacens. S. flaveacens can induce CYP2B1/2 gene expression, while the Sophora- Veratrum group showed weak inhibition. Both single and co-administrated group have some inhibitory effect on CYP3A1 gene expression, while CYP1A gene expression almost has no change in each group.</p><p><b>CONCLUSION</b>These results indicated that compatibility of Sophora and Veratrum in a prescription also have herb-herb interactions based on P450. The possible mechanisms of its incompatible effects need to be further analysised via integrating with metabolic studies.</p>

Veratrum patulum intoxication developed in a group of twenty-three patients / 대한내과학회지

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.

Steroidal alkaloids of from Veratrum dahuricum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the steroidal alkaloids in Veratrum dahuricum.</p><p><b>METHOD</b>The compounds were isolated and purified by various column chromatographic methods. Their structures were identified by spectroscopic analysis.</p><p><b>RESULT</b>Five 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).</p><p><b>CONCLUSION</b>Compound 1 was a new compound, compounds 24 were obtained from the plant for the first time.</p>

Determination of vetatramine in Veratrum nigrum by HPLC-ELSD / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC-ELSD method for determination of vetatramine. in Veratrum nigrum.</p><p><b>METHOD</b>The 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).</p><p><b>RESULT</b>The 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.</p><p><b>CONCLUSION</b>The method may be used as a accurate and reproducible way to determine the content of veratramine in V. nigrum.</p>

Modulation of the activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Panax gingseng and coadministration with Veratrum nigrum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the modulatory effect of Panax gingseng and coadministration with Veratrum nigrum on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver.</p><p><b>METHOD</b>Rat liver microsomal cytochrome P450, b5, aminopyrine N-demethylase(APND), p-nitrophenol-hydroxylase(pNPH)activities were quantitated by UV chromatography. The mRNA expression level of five CYP isoenzymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR).</p><p><b>RESULT</b>P. gingseng coadministrated with V. nigrum obviously decreased the P450 contents of liver microsomes, and the b5 contents. Both single and combined used inhibited the activities of aminopyrine N-demethylase. At the mRNA level, the expression of CYP2C11 markedly induced exposure to V. nigrum, but combinative groups decreased the expression of CYP2C11. The combination of P. gingseng and V. nigrum induced the expression of CYP1A1. P. gingseng has inhibitory effect on CYP2B1/2 and inductive effect used with V. nigrum. The combination of P. gingseng with V. nigrum also induced the expression of CYP3A1.</p><p><b>CONCLUSION</b>P. gingseng used singly has some different modulation effects compared with combinative used, which may occur because of drug-drug interaction based on cytochrome P450. To elucidate the drug-drug interaction, it needs further analysis and metabolism research.</p>