Simultaneous determination and pharmacokinetics of five bufadienolides in rat plasma after oral administration of Chansu extract by SPE-HPLC method

Liang, Yan; Liu, Aihua; Qin, Song; Sun, Jianghao; Yang, Min; Li, Ping; Guo, Dan

doi:10.1016/j.jpba.2007.11.001

Cited by 34 publications

(16 citation statements)

References 29 publications

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“…The mean maximum concentrations (C max ) for the seven bufadienolides ranged from 1.08 to 155.42 ng/mL, and all observed range from approximately 0.42 to 1.33 h post-dose (T max ). The results indicated that the absorption of arenobufagin, cinobufagin, and bufotalin might be rapid (T max less than 1 h), which was in accordance with previously published data [19,20,22].…”

Section: Analytesupporting

confidence: 92%

“…Various analytical methods based on liquid chromatography technology have been developed for the determination of the bufadienolides in biological fluids [18][19][20][21]. However, high limit of quantification, long analysis time, lack of commercial assay kit, the costliness of the instrument and strict requirement for sample pretreatment or could not fulfill oral PK study due to the insufficient sensitivity and specificity, though pronounced.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography–electrospray ionization–tandem mass spectrometry: Application to a pharmacokinetic study

Wang

Peng

Jiang

et al. 2014

Journal of Chromatography B

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Section: Analytesupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography–electrospray ionization–tandem mass spectrometry: Application to a pharmacokinetic study

Wang

Peng

Jiang

et al. 2014

Journal of Chromatography B

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“…In the past 30 years, the rat has been widely used in pharmacokinetic and toxicological studies of Chansu and cinobufagin (Toma et al, 1987;Zhang et al, 1992;Gowda et al, 2003;Xu et al, 2007;Liang et al, 2008;Jiang et al, 2009). However, until now, the differences in the metabolic pathway and metabolic behavior of CB between human and common experimental animals have not been revealed.…”

Section: Discussionmentioning

confidence: 99%

Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human

Ma¹,

Ning²,

Ge³

et al. 2011

Drug Metabolism and Disposition

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ABSTRACT:Cinobufagin (CB), a major bioactive component of the traditional Chinese medicine Chansu, has been reported to have potent antitumor activity. In this study, in vitro metabolism of CB among species was compared with respect to metabolic profiles, enzymes involved, and catalytic efficiency by using liver microsomes from human (HLM), mouse (MLM), rat (RLM), dog (DLM), minipig (PLM), and monkey (CyLM). Significant species differences in CB metabolism were revealed. In particular, species-specific deacetylation and epimerization combined with hydroxylation existed in RLM, whereas hydroxylation was a major pathway in HLM, MLM, DLM, PLM, and CyLM. Two monohydroxylated metabolites of CB in human and animal species were identified as 1␣-hydroxylcinobufagin and 5␤-hydroxylcinobufagin by using liquid chromatography-mass spectrometry and two-dimensional NMR techniques. CYP3A4 was identified as the main isoform involved in CB hydroxylation in HLM on the basis of the chemical inhibition studies and screen assays with recombinant human cytochrome P450s. Furthermore, ketoconazole, a specific inhibitor of CYP3A, strongly inhibited CB hydroxylation in MLM, DLM, PLM, and CyLM, indicating that CYP3A was responsible for CB hydroxylation in these animal species. The apparent substrate affinity and catalytic efficiency for 1␣-and 5␤-hydroxylation of CB in liver microsomes from various species were also determined. PLM appears to have K m and total intrinsic clearance value (V max /K m ) similar to those for HLM, and the total microsomal intrinsic clearance values for CB obeyed the following order: mouse > dog > monkey > human > minipig. These findings provide vital information to better understand the metabolic behaviors of CB among various species.

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“…Secretions of the postauricular and skin glands of Bufo gargarizans and Duttaphrynus melanostictus have been used as a traditional Chinese medicine (TCM) in numerous diseases, including cancers, heart failure and sore throat (16). A previous study suggested cardiac glycosides as potent inhibitors of cancer cell growth (17).…”

Section: Introductionmentioning

confidence: 99%

Effect of arenobufagin on human pancreatic carcinoma cells

et al. 2017

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Abstract. Pancreatic carcinoma (PC) is a deadly form of cancer with poor overall survival. Currently, chemotherapy such as gemcitabine and 5-fluorouracil (5-FU) are the most popular medications that can improve survival, but rapid drug-resistance makes the search for more effective drugs urgent. Upon looking for natural components to treat PC, it was found that arenobufagin, a cardiac glycosides-like compound, showed significant effects on the gemcitabine-resistant pancreatic carcinoma cell line Panc-1 and the gemcitabine-sensitive cell line ASPC-1 at nanomolar concentrations. The present study used MTT and clonogenic survival assays to examine survival and proliferation, and western blotting to assess changes in the associated mitogen activated protein kinase and phosphoinositide 3-kinase pathways and expression of apoptosis-related proteins. The current study also detected the cell cycle by flow cytometry. Arenobufagin inhibited cell survival and proliferation, decreased the phosphorylation of key downstream proteins of K-Ras, including protein kinase B and extracellular signal related kinase, induced cell cycle G2/M phase arrest and apoptosis, and downregulated the level of phosphorylated epidermal growth factor receptor. Notably, the present data also showed that arenobufagin can enhance the sensitivity of PC cells to gemcitabine and 5-FU. In conclusion, arenobufagin could enhance the effect of gemcitabine and 5-FU on PC cells by targeting multiple key proteins. Therefore, arenobufagin has potential as anadjuvant therapy for the treatment of PC.

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Simultaneous determination and pharmacokinetics of five bufadienolides in rat plasma after oral administration of Chansu extract by SPE-HPLC method

Cited by 34 publications

References 29 publications

Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography–electrospray ionization–tandem mass spectrometry: Application to a pharmacokinetic study

Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography–electrospray ionization–tandem mass spectrometry: Application to a pharmacokinetic study

Comparative Metabolism of Cinobufagin in Liver Microsomes from Mouse, Rat, Dog, Minipig, Monkey, and Human

Effect of arenobufagin on human pancreatic carcinoma cells

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