Determination of a potential antitumor quassinoid in rat plasma by UPLC–MS/MS and its application in a pharmacokinetic study

Zhang, Qiang; Yuan, Yonghui; Cui, Jianchun; Xiao, Tingting; Deng, Zhipeng; Jiang, Daqing

doi:10.1016/j.jpba.2016.02.046

Cited by 8 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They were randomly divided into BR-SMEDDS group and BR-suspension group for oral administration (6 mg/kg BR in content). The dosage was selected based on previous report (Zhang et al., 2016b ) and our preliminary experiment. To prepare the suspension, BR was weighed and then suspended in 0.5% (wt/vol) sodium carboxymethycellulose (CMC-Na) solution to the concentration of 0.6 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice

et al. 2017

View full text Add to dashboard Cite

Brusatol (BR) is one of the main bioactive components derived from Brucea javanica, a medicinal herb historically used in the treatment of dysenteric disorders (also known as ulcerative colitis(UC)). Due to its poor aqueous solubility, a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) nanoformulation with smaller size, higher negative zeta potential and drug content, and excellent stability was developed. The appearance of BR-SMEDDS remained clear and transparent, and transmission electron microscopy showed microemulsion droplets to be spherical with homogeneous distribution. Pharmacokinetic parameters indicated that oral bioavailability was greatly improved by BR-SMEDDS as compared with aqueous suspension. Meanwhile, the anti-colitis activity of BR-SMEDDS was evaluated on dextran sodium sulfate (DSS)-induced colitis mice model. The result illustrated that the nano-formation significantly reduced the body weight loss, recovered colon length, decreased disease activity index and microscopic score, regulated immune-inflammatory cytokines, diminished oxidative stress and repressed the colonic expression of myeloid differentiation factor 88 (MyD88), toll-like receptor 4 (TLR4) and nuclear factor kappa B p65 (NF-κB p65) proteins. Our findings demonstrated for the first time that BR could effectively attenuate colonic inflammation in mice, at least partially, via favorable regulation of anti-oxidative and anti-inflammatory status and inhibition of the TLR4-linked NF-κB signaling pathway. The BR nano-formulation was superior to BR suspension and sulphasalazine, in treating experimental UC, and exhibited similar effect with azathioprine, with much smaller dosage. The enhanced anti-UC effect of BR might be intimately associated with the improved pharmacokinetic property by SMEDDS. The developed nano-delivery system might thus be a promising candidate for colitis treatment.

show abstract

Section: Methodsmentioning

confidence: 99%

“…The method of plasma sample preparation was determined as previously described by Zhang et al. ( 2016b ). Briefly, 100 µL plasma was mixed with 10 µL brucein D (200 ng/mL, internal standard) and 500 µL ethyl acetate in a vortex mixer for 3 min.…”

Section: Methodsmentioning

confidence: 99%

Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Even though the LLOQ of this method is higher than that of Zhang's study (Zhang et al, 2016), the phosphate-buffered saline for sample pre-treatment was omitted in our method. Even though the LLOQ of this method is higher than that of Zhang's study (Zhang et al, 2016), the phosphate-buffered saline for sample pre-treatment was omitted in our method.…”

Section: Discussionmentioning

confidence: 93%

“…In this study, the plasma pharmacokinetic and elimination of brusatol in rats after intravenous dosing was studied using an efficient and sensitive HPLC-MS/MS method. Even though the LLOQ of this method is higher than that of Zhang's study (Zhang et al, 2016), the phosphate-buffered saline for sample pre-treatment was omitted in our method. Furthermore, this method is suitable for not only blood, but also urine and feces.…”

Section: Discussionmentioning

confidence: 93%

Pharmacokinetic, metabolic profiling and elimination of brusatol in rats

Guo

Yuan

et al. 2018

Biomedical Chromatography

View full text Add to dashboard Cite

Brusatol, a quassinoid isolated from the traditional Chinese medicine Brucea javanica, has been reported to be an inhibitor of Nrf2 pathway and has great potential to be developed into a novel chemotherapeutic adjuvant. However, the in vivo process of brusatol has not been comprehensively explained yet. Therefore, this paper focused on the pharmacokinetic metabolism and excretion of brusatol in rats using a simple and reproducible LC-MS/MS method. The results indicated that the plasma concentration of brusatol decreased rapidly; the average cumulative excretion rate in urine was 5.82% during 24 h, and 0.71% in bile during 12 h. High-resolution mass spectrometry was applied for the identification of metabolites; as a result, four metabolites were detected and the structure was tentatively deduced on the base of the MS data, Compound Discoverer 2.0 and Mass Frontier 7.0 software. Hydroxylation, hydrolysis and glucuronidation were suggested as major metabolic pathways in vivo. The in vivo process and detection of metabolites of brusatol might improve the understanding of the mechanism of its anticancer effect and provide valuable information for its safety estimation, which will be essential to the new drug development.

show abstract

“…The pharmacokinetics of brusatol has been examined in three articles [138][139][140]. Brusatol undergoes rapid absorption and distribution but is metabolized slowly after intravenous administration [138][139][140].…”

Section: Pharmacokinetics Of Brusatolmentioning

confidence: 99%

Brusatol modulates diverse cancer hallmarks and signaling pathways as a potential cancer therapeutic

Guo

Huang

Tian

2022

Acta Materia Medica

View full text Add to dashboard Cite

Cancer is a consequence of uncontrolled cell proliferation that is associated with cell-cycle disruption. It is a multifactorial disease that depends on the modulation of numerous oncogenic signaling pathways and targets. Although a battle against cancer has been waged for centuries, this disease remains a major cause of death worldwide. Because of the development of resistance to current anticancer drugs, substantial effort has been focused on discovering more effective agents for tumor therapy. Natural products have powerful prospects as anticancer drugs. Brusatol, a component isolated from the plant Brucea javanica, has been demonstrated to efficiently combat a wide variety of tumors. Extensive studies have indicated that brusatol exhibits anticancer effects by arresting the cell cycle; promoting apoptosis; inducing autophagy; attenuating epithelial-mesenchymal transition; inhibiting migration, invasion and angiogenesis; and increasing chemosensitivity and radiosensitivity. These effects involve various oncogenic signaling pathways, including the MAPK, NF-κB, PI3K/AKT/mTOR, JAK/STAT and Keap1/Nrf2/ARE signaling pathways. This review describes the evidence suggesting that brusatol is a promising drug candidate for cancer therapeutics.

show abstract

Determination of a potential antitumor quassinoid in rat plasma by UPLC–MS/MS and its application in a pharmacokinetic study

Cited by 8 publications

References 10 publications

Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice

Characterization of brusatol self-microemulsifying drug delivery system and its therapeutic effect against dextran sodium sulfate-induced ulcerative colitis in mice

Pharmacokinetic, metabolic profiling and elimination of brusatol in rats

Brusatol modulates diverse cancer hallmarks and signaling pathways as a potential cancer therapeutic

Contact Info

Product

Resources

About