Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach

Chen, Ang; Zhou, Xiaojing; Tang, Shuowen; Liu, Mingyao; Wang, Xin

doi:10.1038/srep28482

Cited by 31 publications

(15 citation statements)

References 43 publications

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“…In particular, Ca-neuromycin inhibitors are mainly metabolized by the CYP3A4 enzyme, which is a metabolic enzyme in the liver. The CYP3A4 enzyme in the human liver is equivalent to the CYP3A2 enzyme in the rat liver [29,30]. In our previous study, we showed that cytochrome oxidase CYP3A and drug efflux pump P-gp were two major influencing factors in drug metabolism.…”

Section: Discussionmentioning

confidence: 98%

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

et al. 2020

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Background: The anti-immunological rejection therapy for small-for-size syndrome (SFSS) after live donor liver transplantation (LDLT) play a central role in keeping graft survival. The hepatocyte number and grafts function has undergone real-time changes with the proliferation and apoptosis of the grafts after reperfusion. Lacking an accurate and effective treatment regiments or indicators to guide the use of immunosuppressive drugs in SFS liver transplantation has made immunotherapy after SFS liver transplantation an urgent problem to be solved. Herein, we established small-for-size (SFS) and normal size liver transplantation model in rats to explore the effective indicators in guiding immunotherapy, to find an effective way for overcoming SFSS.Methods: Lewis rats (donors) and BN rats (recipients) were used to mimic allograft liver transplantation and treated with tacrolimus. Local graft immune response was analyzed through haematoxylin and eosin and immunohistochemistry. Flow cytometry was used to assess the overall immune status of recipient. The pharmacokinetics mechanism of immunosuppressive drugs was explored through detecting CYP3A2 expression at mRNA level and protein levels. Results:The results showed the local immune reaction of SFS grafts and systemic immune responses of recipient were significantly increased compared with those in normal size grafts and their recipient at four days after liver transplantation. Regression equation was used to regulate the tacrolimus dose which not only controlled tacrolimus serum concentration effectively but alleviated liver damage and improved survival rate.Conclusions: This study showed that AST level and tacrolimus serum concentrations are effective indicators in guiding immunotherapy. Regression equation (T D = − 0.494T C -0.0035AST + 260.487) based on AST and tacrolimus serum concentration can be used as a reference for adjustment of immunotherapy after SFS liver transplantation, which is applicable in clinical practice.

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Section: Discussionmentioning

confidence: 98%

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

et al. 2020

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“…CYP3A4 followed by CYP2B6, 2C9, 2D6, 2C19, 2E1, 1A2, and 2A6 in sequence are still considered as the main metabolic pathways in CYP-mediated metabolic interactions, although new allelic forms of CYPs have been identified [ 15 , 27 , 28 ]. Therefore, we investigated the inhibitory effects of sauchinone on eight CYP isoforms using a cocktail probe assay in HLMs to understand potential sauchinone–drug interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Actually, long-term intakes of herbs tend to cause TDI which can display late inhibition of metabolic enzymes. Cases of TDI such as plumbagin, silybin, and extract of Cassia abbreviata have been reported in HDIs [ 27 , 31 , 32 ]. Particularly high dose administration of herbs (e.g., g unit of administered herbs) can easily inhibit CYPs.…”

Section: Discussionmentioning

confidence: 99%

Enzyme Kinetics and Molecular Docking Studies on Cytochrome 2B6, 2C19, 2E1, and 3A4 Activities by Sauchinone

et al. 2018

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Sauchinone, an active lignan isolated from the aerial parts of Saururus chinensis (Saururaceae), exhibits anti-inflammatory, anti-obesity, anti-hyperglycemic, and anti-hepatic steatosis effects. As herb–drug interaction (HDI) through cytochrome P450s (CYPs)-mediated metabolism limits clinical application of herbs and drugs in combination, this study sought to explore the enzyme kinetics of sauchinone towards CYP inhibition in in vitro human liver microsomes (HLMs) and in vivo mice studies and computational molecular docking analysis. In in vitro HLMs, sauchinone reversibly inhibited CYP2B6, 2C19, 2E1, and 3A4 activities in non-competitive modes, showing inhibition constant (Ki) values of 14.3, 16.8, 41.7, and 6.84 μM, respectively. Also, sauchinone time-dependently inhibited CYP2B6, 2E1 and 3A4 activities in vitro HLMs. Molecular docking study showed that sauchinone could be bound to a few key amino acid residues in the active site of CYP2B6, 2C19, 2E1, and 3A4. When sibutramine, clopidogrel, or chlorzoxazone was co-administered with sauchinone to mice, the systemic exposure of each drug was increased compared to that without sauchinone, because sauchinone reduced the metabolic clearance of each drug. In conclusion, when sauchinone was co-treated with drugs metabolized via CYP2B6, 2C19, 2E1, or 3A4, sauchinone–drug interactions occurred because sauchinone inhibited the CYP-mediated metabolic activities.

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“…In another study ( Table 2), Sumsakul et al found that changing the species (Wistar vs. Sprague-Dawley rats) showed significant impact on oral pharmacokinetics of PLB attributed to its limited biopharmaceutical properties such as high lipophilicity (log P 3.04) and insolubility in water ( Table 2) [3]. Chen et al investigated the effects of PLB on CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in human and rat liver [23]. In humans, PLB was not only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-competitive inhibitor of CYP1A2 with K i values no more than 2.16 lM.…”

Section: Biopharmaceutics Of Plbmentioning

confidence: 99%

Current development in novel drug delivery systems of bioactive molecule plumbagin

Rajalakshmi¹,

Vyawahare²,

Pawar

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Plumbagin (PLB), a member of the quinine family, mainly found in the plant Plumbago zeylanica Linn., potentially exhibit anticancer, anti-inflammatory, anti-oxidant, antifungal, neuroprotective, hypolipidemic and antibacterial activities. However, it has been well known that the application of PLB was limited owing to its water insolubility, instability and poor bioavailability. For decades, many attempts have been made to compensate for these disadvantages with the development of improved delivery platforms as the feasible approaches. This review aims to describe the various studies supporting the biopharmaceutical aspects of PLB. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of PLB such as solubility, stability and bioavailability. Also, this paper summarizes the recent works on the design and development of novel delivery systems of PLB such as liposomes, niosomes, microsphares, nanoparticles, micelles, complexization, metal nanoparticles, crystals modification, etc., with the goal of harnessing the true difficulties of this multifunctional agent in the clinical arena.

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Evaluation of the inhibition potential of plumbagin against cytochrome P450 using LC-MS/MS and cocktail approach

Cited by 31 publications

References 43 publications

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

Enzyme Kinetics and Molecular Docking Studies on Cytochrome 2B6, 2C19, 2E1, and 3A4 Activities by Sauchinone

Current development in novel drug delivery systems of bioactive molecule plumbagin

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