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Enhancement of tyrosinase inhibition of the extract of Veratrum patulum using cellulase.

Inhibitors of melanin biosynthesis were screened by using three different methods. The extract of Veratrum patulum contains hydroxystilbene compounds that are potent tyrosinase inhibitors. We evaluated the enzyme inhibitory property on the mushroom tyrosinase of hydroxystilbene compounds including resveratrol, oxyresveratrol, and their analogs. Biotransformation using cellulase of the whole extract brought about an increase in the inhibitory activity of the products on mushroom tyrosinase. The enhancement of tyrosinase inhibition is supposed to increase the concentration of aglycon, which has superior inhibitory activity to its glycoside. Eventually, melanin biosynthesis was inhibited by the enhanced tyrosinase inhibitory activity of the extract. This result indicated that deglycosylation of stilbene compounds has exerted more effective inhibition on the enzyme than that of the unprocessed plant extract.

Agaricales↗

Expression of Veratrum alkaloid teratogenicity in the mouse.

Jervine, a steroidal alkaloid found as a minor constituent in the teratogenic range plant Veratrum californicum, has produced similar terata in sheep, rabbit, hamster, and chick, although the sensitivity to the alkaloid varies in the different species. Sprague Dawley rats and Swiss Webster mice are relatively insensitive. The aim of this study was to determine the teratogenic potential of jervine in three strains of mice and to ascertain if the response is strain dependent. One strain, Swiss N:GP(S), was retested since a Swiss Webster strain had been found previously to be jervine-resistant. In addition, we tested C57BL/6J and A/J, which are known to differ in their response to the teratogenic action of steroids and vitamin A. Mice were treated by gavage with single doses of jervine (70, 150, or 300 mg/kg body weight) on either day 8, 9, or 10 of gestation. Jervine was teratogenic to C57BL/6J and A/J mice but not to N:GP(S). The induced terata included cleft lip with or without cleft palate, isolated cleft palate, mandibular micrognathia or agnathia, and limb malformations. Fetal teratogenicity and maternal and fetal toxicity were highly correlated. The prevalence of each defect and fetal death was a function of strain, dose, and time of treatment. Maternal death was higher in C57BL/6J than in A/J mice. Although some of the terata were similar, the response pattern between strains was different from corticosteroids and vitamin A for both sensitive period and the strain dose response. An effect on differentiation of chondrocyte precursors may account for many of the defects, but an earlier lethal effect on differentiation of neural crest cells or precordal mesenchyme may also occur.

Animals↗

Dietary poisoning with Veratrum album--a report of two cases.

Veratrum album is a poisonous plant that can easily be mistaken for the yellow gentian, Gentiana lutea, used in beverages. Two adult men were brought to the emergency department six hours after drinking gentian spirit. Each presented with nausea and vomiting, preceded by headache, developed within one hour after ingestion, and followed by diarrhea in one of the patients. Vital signs were normal except for heart rates of 42 and 45 beats per minute in the two patients, respectively. Laboratory findings were unremarkable. Electrocardiograms revealed sinus bradycardia. Activated charcoal and antiemetics were given and the patients were admitted for observation of signs of toxicity. The further clinical course was uneventful. Heart rates returned to normal within eight hours after admission. Retrospective investigation of the gentian beverage confirmed that V. album was mistaken for G. lutea. Patients with clinical toxicity following unintentional ingestion of V. album should be kept under observation and generally recover with supportive care.

Aged↗

Inhibition of limb chondrogenesis by a Veratrum alkaloid: temporal specificity in vivo and in vitro.

It has been demonstrated that jervine, a steroidal alkaloid derived from plants of the genus Veratrum, exerts teratogenic effects in several animal species. Defects were restricted to structures which depend upon normal chondrogenesis for their development. Here we report studies of the temporal specificity of cellular sensitivity using limb bud mesenchyme cells obtained from Day 10 mouse embryos. These cells, when grown as high-density "spot" cultures, undergo chondrogenesis in vitro. Prior to differentiation, exposure of limb cell cultures to jervine suppressed subsequent accumulation of cartilage proteoglycans. Treatment after differentiation had no significant effect. Additionally, there was a genetic component to jervine sensitivity: C57BL/6J mice were sensitive, whereas NIH Swiss-Webster mice were insensitive. This strain-dependent difference was observed both in vivo and in vitro, supporting the validity of limb mesenchyme spot cultures as a model for jervine-induced teratogenicity. Our studies indicate that jervine acts specifically during an early phase of the differentiation of mesenchyme into cartilage. It is likely that a specific stem cell population is the target tissue of this compound.

Animals↗

Towards an evidence-based repertory: clinical evaluation of Veratrum album.

The analysis of data collected by applying information technology in daily practice opens the possibility of validating homeopathic prescribing symptoms. The author has collected data on repertory rubrics, homeopathic medicines prescribed, and clinical outcomes, for 16 years. As an example of clinical verification the outcomes of patients prescribed Veratrum album are correlated against rubrics. Remarkable results were obtained when Verat-a was presented to 24 patients, 52 rubrics were used. The data were analysed using the classical method and the likelihood ratios method. There is good correlation in the results given by these methods. Among the most important symptoms of Verat-a are: ailments from mortification, vomiting and cough in Spring.

Drug Prescriptions↗

Blood-pressure lowering, positive chronotropy and inotropy by the Veratrum alkaloids germidine and germerine but negative chronotropy by veratridine in mice.

Germidine and germerine, the Veratrum alkaloids lowered blood pressure accompanied with positive chronotropy and inotropy in mice. Germerine was more potent than germidine in both blood-pressure lowering and positive inotropy, whereas veratridine produced negative chronotropy and positive inotropy. An acyl group (an acetyl or a 2-methylbutyroyl group) at 3-O-R1 position and a 2-methylbutyroyl group at 15-O-R2 position in germine were important to produce the positive inotropy and chronotropy. The presence of a veratroyl group at 3-O-R1 position and a free hydroxyl group at 15-O-R2 position may be essential to produce the negative chronotropy by veratridine. The positive inotropy by germidine and veratridine may be due to TTX-resistant Na+ channel activation.

Animals↗

LC-EI-MS determination of veratridine and cevadine in two fatal cases of Veratrum album poisoning.

We report two fatal poisonings due to the ingestion of plant material. The two deceased were discovered in the water of a mountain lake about one month after the postmortem immersion of the corpses. Macroscopic examination of the stomachs revealed the presence of a very large number of small blackish granules, which were later identified as seeds of a Veratrum species. Veratridine and cevadine were identified and quantitated by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Measured blood concentrations were 0.17 and 0.40 ng/mL for veratridine and 0.32 and 0.48 ng/mL for cevadine. The absence of other toxic substance led to the assumption that this massive ingestion was the cause of death, although the circumstances surrounding intake remained unknown.

Adult↗

Growth substances from Veratrum tenuipetalum.

Young leaves and buds of Veratrum tenuipetalum yielded non-indolic growth accelerators and inhibitors in the acidic ether fraction. The titer of accelerators decreased while the inhibitors increased as leaves matured. This was also true when comparing extracts of immature and fruiting inflorescences. Indole 3-acetic acid was at no time detected in leaf, bud, and inflorescence extracts but indole 3-acetyl-aspartic acid was readily recovered from all of these. The alkaline ether fraction of leaf base meristems, buds, roots, and rhizomes was rich in crystalline and amorphous alkaloids and phenolic acids. Reducing the quantity of major substances through crystallization, precipitation, and filtration permitted thin film chromatographic separation of the minor alkaloids and phenolic acids in the presence of the major ones. The unchromatographed mixture, and also certain of the purified major and minor alkaloids studied, strongly inhibited growth in germinating oat and winter rye seeds. In addition, profound changes in morphology and cytology of the seminal roots resulted. DNA disappeared partially to completely from affected tissue in 2 day germinated seeds.

Plant Extracts↗

Poisoning with Veratrum-containing sneezing powders.

1 Nine cases of accidental poisoning of children with sneezing powder are reported. Symptoms, besides sneezing, included gastrointestinal disturbances and syncope, whilst examination demonstrated bradycardia and hypotension. 2 The powder, as supplied, carried no information on its constituents but Veratrum alkaloids were identified on analysis. The signs and symptoms observed were compatible with poisoning from these compounds. 3 As a result of these observations, it was possible to trace the manufacturers and a change was made to a safer formulation. This example emphasises the value of toxic vigilance by Poison Control Centres.

Adolescent↗

Veratrum alkaloids in sneezing-powder a potential danger.

Sneezing-powders containing pulverized root of veratrum album (white hellebore) have recently been marketed in the Scandinavian countries. The powder, imported from the Federal Republic of Germany, has caused severe intoxications.

Child↗

The nature of congenital limb defects induced in lambs by maternal ingestion of Veratrum californicum.

Groups of ewes were gavaged Veratrum californicum root-rhizome material over various 3 day periods during early gestation and their late-term fetuses examined. Resulting from gavage near day 29 were shortening of fetal metacarpal, metatarsal and tibial bones. Fibulae bowed severely when tibiae were shortened. Medial bowing of forelimbs at the fetlocks resulted from unequal shortening of fused metacarpi. Severe joint articular surface defects and arthrogryposis were present in some of the lambs from treatment ewes. There was bilateral and twinning symmetry in limb bone shortening. Severity of limb defects varied with gestational stage at time of gavage.

Animals↗

Myocardial responses to acetylstrophanthidin during veratrum alkaloid refractoriness.

Studies were undertaken in the isolated blood perfused dog heart to determine the nature of the myocardial refractoriness induced by veratrum alkaloids. The initial intracoronary injection of cryptenamine acetates (Unitensin) was always associated with an increase in myocardial contractility and a loss of myocardial potassium. Subsequent doses produced refractoriness with respect to both the contractile and potassium responses. Acetylstrophanthidin still produced an inotropic and potassium losing effect duct of the glycoside was potentiated whereas the contractile response was not.

Animals↗

Effects of Veratrum nigrum alkaloids on central catecholaminergic neurons of renal hypertensive rats.

AIM: To study the central hypotensive mechanism of Veratrum nigrum L var ussurience Nakai alkaloids (VnA) in renal hypertensive rats(RHR). METHODS: The quantitative method of immunocytochemistry (ICC) was used to observe and detect the effect of VnA (30 micrograms.kg-1, i.v.) on activity of central catecholaminergic (CA) neurons of C1, C2, A1, and A5 areas in RHR. RESULTS: VnA increased the immunoreactivity (IR) of tyrosine 3-monooxygenase (TM)-immunopositive (IP) neurons of C1, C2, and A5 areas in RHR experimental group compared with RHR control group [positive units: (1.9 +/- 0.4), (1.18 +/- 0.23), (1.2 +/- 0.4) vs (0.15 +/- 0.22), (0.31 +/- 0.16), (0.69 +/- 0.20), respectively]; IR of TM-IP neurons of C1 and C2 areas in RHR control group was decreased compared with sham-operated group [positive units: (0.15 +/- 0.22), (0.31 +/- 0.16) vs (1.45 +/- 0.29), (1.36 +/- 0.25), respectively]. CONCLUSION: VnA increased the activity of central CA neurons in RHR to exert its hypotensive effect.

Animals↗

[Chemical research on stilbenes from Veratrum macckii Reg].

OBJECTIVE: To study the components in rhizome of Veratrum macckii. METHODS: Column chromatography and preparative thin layer chromatography with silica gel were employed for the isolation and purification of constituents. The structures were elucidated by IR, MS and 1H-NMR analysis. RESULTS: Two compounds were obtained and elucidated as resveratrol and 2,3',4,5'-tetrahydroxystilbene. CONCLUSION: The two compounds were separated from V. macckii for the first time.

Drugs, Chinese Herbal↗

[Modulation of the activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Panax gingseng and coadministration with Veratrum nigrum].

OBJECTIVE: 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. METHOD: 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). RESULT: 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. CONCLUSION: 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.

Aminopyrine N-Demethylase↗

Effects of nerve stimulation on ion transport in mouse jejunum: responses to Veratrum alkaloids.

Veratrum alkaloids were used to examine the effect of neural stimulation on intestinal ion transport in full-thickness (intact) and serosally stripped (mucosal) preparations of mouse jejunum. When applied to the serosal media of mucosal preparations, veratrine or veratridine evoked a biphasic increase in transmural potential difference and short-circuit current, consisting of phasic and tonic increases of both bioelectric parameters without a change of tissue conductance; these responses were blocked by pretreatment with tetrodotoxin, but unaffected by pretreatment with atropine, naloxone or yohimbine. In ion flux experiments, neural stimulation of mucosal tissues produced changes of unidirectional fluxes that corresponded with an increase in net Cl- secretion and a reduction of net Na+ absorption, supporting a net secretory role for neurons that were associated with the intestinal mucosa. In intact jejunal preparations, neural stimulation by veratrine or veratridine caused a tetrodotoxin-sensitive reduction of basal transmural potential difference and short-circuit current and a significant increase of tissue conductance. Flux studies on intact tissues failed to reveal the ionic basis for the effects of nerve stimulation by veratridine in these tissues. Nonetheless, the neurally evoked reduction of short-circuit current was attenuated by yohimbine pretreatment, but unaffected by naloxone or atropine, suggesting an involvement of alpha-2 adrenoceptors in the mediation of this effect. These findings demonstrate the existence of endogenous neurotransmitter systems that play opposing roles in the regulation of mucosal ion transport in the small intestine of the mouse.

Action Potentials↗

[Electrocardiographic studies of patients with acute hellebore (Veratrum album) poisoning].

In 12 patients, 20 to 80 years of age, 6 men and 6 women, with acute hellebore (Veratrum album) intoxication the electrocardiographic changes were studied. In 10 of them a characteristic ECG pattern was found: sinus bradycardia 38-40/m, shortening of the interval PQ up to 0.12-0.08 s and QTc up to 0.36-0.32 s, slow intraventricular conduction--transitory right and incomplete left bundle-branch block, rhythm disorders--atrial and substitutional ventricular extrasystoles, nodal rhythm (I patient), disturbed ventricular repolarization--depression of ST-segment, low and (or) pointed T waves. The authors are of the opinion that the bradycardia is due to a reflexively increased vagal tonus but the other changes of the ECG are caused by the direct toxic action of the hellebore alkaloids on the myocardium. This suggestion is supported by the fact that atropine corrects the bradycardia but not the other pathological changes of the ECG. They are beneficially influenced by the fast elimination of the toxins and the application of cardiotropic means--atriphos, cocarboxylase, vitamins of the group B.

Acute Disease↗