Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography–tandem mass spectrometry

Chen, Lihua; Zhang, Huimin; Guan, Zhiwei; Zhu, Weifeng; Wu, Yi Long; Guan, Yongmei; Wang, Sen; Liu, Hongning

doi:10.1016/j.jep.2012.09.054

Cited by 25 publications

(22 citation statements)

References 23 publications

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“…The pharmacokinetics of peimine, peiminine and verticinone, major steroidal alkaloids from genus Fritillaria of Liliaceae, were significantly influenced by gender in rats, and slower elimination of them was observed in male rat plasma (80,81), which was consistent with the phenomenon found in pharmacokinetic behavior of steroidal alkaloid veratramine. The enterohepatic circulation was also reported after peimine was administrated to rats (80). However, these studies only hypothesized that sulfation was one of the reasons for the gender-related pharmacokinetics of steroidal alkaloids without experimental verification (81).…”

Section: Discussionsupporting

confidence: 78%

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: Discussionsupporting

confidence: 78%

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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“…44 In addition, Wang et al 45 gave male Beagle dogs oral administration of 1 g/kg Fritillaria ussuriensis Maxim and F. thunbergii Miq, respectively. After oral administration of 4.25 g/kg Fritillaria thunbergii Miq.…”

Section: Discussionmentioning

confidence: 99%

Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca²⁺/CaMKII/JNK pathway

Tan

Zhang

Yang

et al. 2019

J of Cellular Biochemistry

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Prostate cancer (PC) is one of the most common malignant tumors in man. Peimine (PM) is a bioactive substance isolated from Fritillaria. Previous studies have shown that PM could inhibit the occurrence of a variety of cancers. However, the roles of PM in PC and its related mechanism have not been elucidated. Calcium (Ca2+) is an important intracellular messenger involved in a variety of cell processes. In this study, we found that the appropriate doses of PM (2.5, 5, and 10 μM) significantly inhibited the growth of PC cells (DU‐145, LNCap, and PC‐3), but has no significant effect on normal prostate cells (RWPE‐1). In addition, PM treatment inhibited the invasion and migration of PC‐3 cells and blocked the epithelial‐mesenchymal transition process. These effects were exhibited a dose‐dependent manner. Furthermore, the current results also showed that PM treatment significantly increased the Ca2+ concentration, the increased Ca2+ promoted the phosphorylation of Ca2+/calmodulin‐dependent protein kinase II (CaMKII) and c‐Jun N‐terminal kinase (JNK), further inhibited the growth and invasion of PC‐3 cells, and induced its apoptosis. Ca2+ chelator BAPTA‐AM (1 μM) could counteract the increase of intracellular Ca2+ concentration. Similarly, JNK pathway inhibitor SP600125 (10 μM) also inhibited cell growth and invasion and induced apoptosis. In addition, experiments in nude mice showed that PM inhibited tumor formation through Ca2+/CaMKII/JNK signaling pathway. In conclusion, our results show that PM inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+/CaMKII/JNK pathway.

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“…In female rats, a previous study (Austin et al, 2003) reported that doses of 1.0 mg and 10 mg of PFOS/kg/day for 14 days did not modify the dopamine content in the paraventricular and in the medial preoptic nuclei (both nuclei located in the anterior hypothalamus) as a possible result of the lesser sensitivity to this chemical in female rats than in male ones (Chen et al, 2013). Moreover, a very lofty dose of PFOS (250 mg/kg) did not modify the dopamine concentration in the cerebellum or in the whole brain in male rats (Sato et al, 2009) but a later study showed a decrease of dopamine and DOPAC content in the caudate and putamen in mice treated with 10.75 mg of PFOS/kg/day for three months (Long et al, 2013).…”

Section: Discussionmentioning

confidence: 89%

“…These apparent differences could be due to the specific prolactin activity through gestation and to the special hormone status, which occurs during this physiological period (L opez-Fontana et al, 2012). Furthermore, in rats, a sex-dependent sensitivity against PFOS exposure cannot be ruled out (Chen et al, 2013). On the other hand, PFOS induces development toxicity, so it might be interesting to analyze the concentration of prolactin-like hormones in the placenta.…”

Section: Discussionmentioning

confidence: 99%

Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion

Salgado

Pereiro

López-Doval

et al. 2015

Food and Chemical Toxicology

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Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography–tandem mass spectrometry

Cited by 25 publications

References 23 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

Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca²⁺/CaMKII/JNK pathway

Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion

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Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography–tandem mass spectrometry

Cited by 25 publications

References 23 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

Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+/CaMKII/JNK pathway

Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion

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Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca²⁺/CaMKII/JNK pathway