Determination of resibufogenin and cinobufagin in heart-protecting musk pill by HPLC

Hong-tao, Song; Guo, Tao; Bi, Kaishun; Wang, Huirong; Zhang, Ruhua

doi:10.1002/(sici)1099-0801(200004)14:2<130::aid-bmc929>3.0.co;2-1

Cited by 28 publications

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“…One of the major active ingredients of Chan Su, bufalin, is known to exhibit a variety of biological activities. Bufalin has been shown to induce apoptosis in human leukemia HL-60 cells and human tumor cells [12][13][14][15][16][17][18] . In preliminary experiments, bufalin has shown modest inhibition on hepatic CYP3A4.…”

Section: Discussionmentioning

confidence: 99%

“…The facts described above indicated that CYP3A4 inhibition in the presence of bufalin was a major cause of the changes in the pharmacokinetics of midazolam. In conclusion, the present study demonstrates that bufalin, which has been reported to exhibit significant anti-tumor activity [12][13][14][15][16][17][18] , showed a modest but significant inhibition of CYP3A4 both in vitro and in vivo, which was confirmed by bioequivalence evaluation. The likelihood of an in vivo interaction between bufalin and CYP3A4-metabolized drugs in humans might not be negated, although more data on multiple-dose pharmacokinetics should be collected to complete the inhibitory profile, and further experiments need to be carried out to determine whether bufalin could be metabolized by the CYP3A4 system or whether its metabolites could inhibit the enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…Chan Su is the major component of such popular traditional Chinese herbal remedies as Liu-shen-wan, She-xiang-baoxin-wan and Kyushin [13,16] . These traditional Chinese herbal remedies have been widely applied in China and other Asian countries, and are currently used as alternatives to Western treatments.…”

Section: Introductionmentioning

confidence: 99%

“…Bufalin is known to increase vasoconstriction, vascular resistance and blood pressure, and has been shown to induce apoptosis in human leukemia HL-60 cells, endometriotic stromal cells, and prostate cancer cells. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumor cells by inducing apoptosis and cell cycle arrest [12][13][14][15][16][17][18] . Few studies have examined the interaction of bufalin with prescription medications, and none have been conducted on its impact on the CYP3A4 enzyme system.…”

Section: Introductionmentioning

confidence: 99%

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Bufalin inhibits CYP3A4 activity in vitro and in vivo

Zhang

et al. 2009

Acta Pharmacol Sin

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Aim:To investigate the inhibitory interactions of bufalin and CYP3A4. Methods: Recombinant human CYP3A4 was incubated with bufalin in vitro. Bufalin was administered ig and iv to Wistar rats to further estimate its impact on CYP3A4, and midazolam was given to index the activity of CYP3A4. Results: The IC 50 of bufalin was 14.52 μmol/L. Bufalin affected CYP3A4 activity with increases in AUC 0-t and t 1/2 , and decreases in CL and the formation of 1-hydroxy-midazolam after ig or iv administration of midazolam (P<0.05). An increase in C max after ig bufalin administration (P<0.05) was observed. Conclusion: Bufalin showed a modest but significant inhibition of CYP3A4 both in vitro and in vivo. The likelihood of an interaction between bufalin and the CYP3A4-metabolized drugs in human might not be negated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bufalin inhibits CYP3A4 activity in vitro and in vivo

Zhang

et al. 2009

Acta Pharmacol Sin

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“…Chansu has long been recognized in China and other Asian countries as an important constituent of some famous traditional Chinese medicine (TCM) formulas, such as Liu Shen Wan (Hong et al, 1992), Shexiang Baoxin Wan (Song et al, 2000), and Niu Huang Xiao Yan Wan (Zhou et al, 1992). Cinobufagin (CB) (Fig.…”

Section: Introductionmentioning

confidence: 99%

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

Ma¹,

Ning²,

Ge³

et al. 2011

Drug Metab Dispos

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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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Simultaneous determination of four bufadienolides in human liver by high‐performance liquid chromatography

Wang¹,

Wen²,

Zhang³

et al. 2003

Biomedical Chromatography

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A high-performance liquid chromatographic method for the simultaneous quantitation of four bufadienolides-cinobufotalin, bufalin, cinobufagin and resibufogenin-in human liver was investigated. The procedure involved solid phase extraction of human liver with an Oasis HLB cartridge coupled with reversed-phase HPLC and photodiode array detection. Recoveries obtained from spiked liver for the bufadienolides were better than 70%. The linearity was studied up to 1.2 mg/kg and the detection limits of the method were 0.4 ng for cinobufotalin and bufalin and 0.5 ng for cinobufagin and resibufogenin. The developed method was successfully applied to a lethal poisoning case.

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Determination of resibufogenin and cinobufagin in heart-protecting musk pill by HPLC

Cited by 28 publications

References 0 publications

Bufalin inhibits CYP3A4 activity in vitro and in vivo

Bufalin inhibits CYP3A4 activity in vitro and in vivo

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

Simultaneous determination of four bufadienolides in human liver by high‐performance liquid chromatography

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