Carbon-13 and Proton Nuclear Magnetic Resonance Spectra of Veratrum Alkaloids

Gaffield, William; Benson, Mabry; Lundin, Robert E.; Keeler, Richard F.

doi:10.1021/np50044a014

Cited by 32 publications

(12 citation statements)

References 9 publications

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“…The male-predominant expression and activity of CYP3A were verified to be the major reasons for the gender-dependent pharmacokinetics of indinavir in rats (78). Steroidal alkaloids of Liliaceae mainly possess a C 27 cholestane carbon skeleton with four or five carbocyclic and one heterocyclic rings (3,79). Among the Liliaceae family, genus Veratrum and Fritillaria, two most important steroidal alkaloids containing herbs, were widely used as folk remedies *p < 0.05, significant difference; **p < 0.01, highly significant difference (vs. the same metabolite for male rats).…”

Section: Discussionmentioning

confidence: 99%

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

Lyu

Zhang

Zhou

et al. 2016

AAPS J

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ABSTRACT. Veratramine, a major alkaloid from Veratrum nigrum L., has distinct anti-tumor and antihypertension effects. Our previous study indicated that veratramine had severe toxicity toward male rats. In order to elucidate the underling mechanism, in vivo pharmacokinetic experiments and in vitro mechanistic studies have been conducted. Veratramine was administrated to male and female rats intravenously via the jugular vein at a dose of 50 μg/kg or orally via gavage at 20 mg/kg. As a result, significant pharmacokinetic differences were observed between male and female rats after oral administration with much lower concentrations of veratramine and 7-hydroxyl-veratramine and higher concentrations of veratramine-3-O-sulfate found in the plasma and urine of female rats. The absolute bioavailability of veratramine was 0.9% in female rats and 22.5% in male rats. Further experiments of veratramine on Caco-2 cell monolayer model and in vitro incubation with GI content or rat intestinal subcellular fractions demonstrated that its efficient passive diffusion mediated absorption with minimal intestinal metabolism, suggesting no gender-related difference during its absorption process. When veratramine was incubated with male or female rat liver microsomes/cytosols, significant malepredominant formation of 7-hydroxyl-veratramine and female-predominant formation of veratramine-3-O-sulfate were observed. In conclusion, the significant gender-dependent hepatic metabolism of veratramine could be the major contributor to its gender-dependent pharmacokinetics.

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Section: Discussionmentioning

confidence: 99%

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

Lyu

Zhang

Zhou

et al. 2016

AAPS J

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“…Cyclopamine (11-deoxojervine) obtained from Veratrum californicum (63) . Eggs were sealed with adhesive tape and incubated at 37.5°C until the desired stage of development was reached.…”

Section: Methodsmentioning

confidence: 99%

Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes

Cordero

Marcucio²,

Hu³

et al. 2004

J. Clin. Invest.

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113

131

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One of the most perplexing questions in clinical genetics is why patients with identical gene mutations oftentimes exhibit radically different clinical features. This inconsistency between genotype and phenotype is illustrated in the malformation spectrum of holoprosencephaly (HPE). Family members carrying identical mutations in sonic hedgehog (SHH) can exhibit a variety of facial features ranging from cyclopia to subtle midline asymmetries. Such intrafamilial variability may arise from environmental factors acting in conjunction with gene mutations that collectively reduce SHH activity below a critical threshold. We undertook a series of experiments to test the hypothesis that modifying the activity of the SHH signaling pathway at discrete periods of embryonic development could account for the phenotypic spectrum of HPE. Exposing avian embryos to cyclopamine during critical periods of craniofacial development recreated a continuum of HPE-related defects. The craniofacial malformations included hypotelorism, midfacial hypoplasia, and facial clefting and were not the result of excessive crest cell apoptosis. Rather, they resulted from molecular reprogramming of an organizing center whose activity controls outgrowth and patterning of the mid and upper face. Collectively, these data reveal one mechanism by which the variable expressivity of a disorder such as HPE can be produced through temporal disruption of a single molecular pathway.

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“…20 Cyclopamine treatments were carried out using DMEM-F12 (Invitrogen, Paisley, UK) supplemented with 2% FBS, and the doses were previously described. 14,21 Cells (2 ϫ 10 6 /flask) were seeded in triplicate flasks and allowed to grow to approximately 50% confluence prior to treatment.…”

Section: Treatment With Cyclopaminementioning

confidence: 99%

Hedgehog signalling in colorectal tumour cells: Induction of apoptosis with cyclopamine treatment

Qualtrough

Buda

Gaffield

et al. 2004

Intl Journal of Cancer

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153

138

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Carbon-13 and Proton Nuclear Magnetic Resonance Spectra of Veratrum Alkaloids

Cited by 32 publications

References 9 publications

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes

Hedgehog signalling in colorectal tumour cells: Induction of apoptosis with cyclopamine treatment

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