Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport

Liu, Zuliang; Tang, Tao; Guan, Xuejing; Dong, Wei; Zhang, Jing; Zhao, Guowei; Yang, Ming; Liang, Xin-Li

doi:10.3390/molecules21121606

Cited by 19 publications

(14 citation statements)

References 29 publications

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“…A rhodamine 123 (Rho-123, Thermo Fisher Scientific, Pittsburgh, PA, USA) transport assay was performed to observe the effects of RT and sorafenib on the activity of P-gp as described previously 18,19 . In brief, Huh-7 cells were seeded in a 6-well plate.…”

Section: Effects Of Rt On P-glycoprotein (P-gp) Activitymentioning

confidence: 99%

Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters

Hsieh

Chen

Tsai

et al. 2020

Sci Rep

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To evaluate the effect and mechanism of radiotherapy (RT)-sorafenib pharmacokinetics (PK) in different regimens with conventional or high dose irradiation. Between February 2012 and December 2018, 43 patients with portal vein tumor thrombosis treated with sorafenib plus conventional RT (58%) or stereotactic body radiation therapy (SBRT, 42%) were retrospectively reviewed. In vivo and in vitro studies of concurrent and sequential RT with sorafenib were designed. SBRT resulted in a 3-fold increase in complete recanalization compared to conventional RT group (28% vs. 8%, p = 0.014). Compared to the control group, the area under the concentration vs. time curve (AUC) of sorafenib was increased in the concurrent Rt 2Gy and Rt 9Gy groups and the sequential RT 9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential Rt 2Gy group (p = 0.036). Sequential RT 2Gy and Rt 9Gy increased CYP3A4 activity by 82% (p = 0.028) and 203% (p = 0.0004), respectively, compared to that with the corresponding concurrent regimen. SBRT produced better recanalization than conventional RT with sorafenib. The AUC of sorafenib was modulated by RT. P-gp expression was not influenced by RT. The sequential RT regimen increased CYP3A4 activity that may increase the RT-sorafenib synergy effect and overall sorafenib activity. The biodistribution of sorafenib was modulated by local RT with the different regimens.

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Section: Effects Of Rt On P-glycoprotein (P-gp) Activitymentioning

confidence: 99%

Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters

Hsieh

Chen

Tsai

et al. 2020

Sci Rep

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“…MDCK-MDR1 Cells were obtained from Shanghai Zhongya Institute of Biological Genes Institute (CinoAsia Co., Ltd., Shanghai, China). Cells were cultured as previously described [ 29 , 30 ]. In brief, cells were cultured in high glucose DMEM medium supplemented with 10% fetal bovine serum (FBS), 1% non-essential amino acids, 1% l -glutamine, and a penicillin-streptomycin double antibiotic solution.…”

Section: Methodsmentioning

confidence: 99%

“…The molecular docking study was performed as previously described [ 29 , 30 ]. The three-dimensional protein structure of P-gp (PDB code: 3G60) was searched from the Brookhaven Protein Data Bank (PDB, ).…”

Section: Methodsmentioning

confidence: 99%

“…The CHARMmforce field was applied for geometry optimization. The P-gp residues identified according to previous literatures [ 29 , 30 , 31 ] were used to define an active pocket. The ligand was docked at the defined active site of P-gp using Libdock, and the Libdock score was recorded for analysis, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…P-gp ATPase activity was measured using P-gp-Glo™ assay systems kit according to the manufacturer’s instructions, the method detail of which was also described in our previous study [ 29 ]. The P-gp-Glo™ assay system kit mainly contains recombinant human P-gp membranes, ATP detection substrate, ATP detection buffer., P-gp-Glo™ assay buffer, Mg-ATP, verapamil (a positive control substrate of P-gp), and sodium orthovanadate (Na 3 VO 4 , a P-gp ATPase inhibitor).…”

Section: Methodsmentioning

confidence: 99%

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Reversal Effect of Oxypeucedanin on P-glycoprotein-mediated Drug Transport

et al. 2018

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P-glycoprotein affects the transport of numerous drugs including chemotherapeutic drugs vincristine sulfate (VCR) and docetaxel (DTX), and is one of the main causes for multidrug resistance. Our previous studies have shown that oxypeucedanin (OPD) can enhance the intestinal transit of puerarin and VCR. However, the underlying mechanism is unclear. This study investigated the potential mechanism by which OPD improves P-gp-mediated drug transport. Molecular docking was performed to predict the binding force between OPD and P-gp and the contribution of OPD on P-gp activity. We observed the effect of OPD on the transport of VCR in MDCK-MDR1 cell monolayer and also measured the plasma pharmacokinetic parameters of DTX in the presence and absence of OPD by LC-MS/MS. Moreover, we further investigated the reversal mechanism of OPD on P-gp-mediated drug transport by determining the intracellular accumulation of Rhodamine-123 (Rh123) and P-gp ATPase activity as well as protein expression and mRNA level of P-gp. Our molecular docking results revealed that the binding force between OPD and P-gp was much lower than that between P-gp and verapamil (a P-gp substrate). The transport study in vitro indicated that OPD increased the flux of VCR across MDCK-MDR1 cell monolayer. The in vivo pharmacokinetic parameters data showed OPD increased the absorption of DTX. OPD activated P-gp ATPase activity and enhanced intracellular accumulation of Rh123 in MDCK-MDR1 cells. Western blotting and qRT-PCR outcomes indicated that OPD suppressed P-gp protein expression as well as downregulated P-gp mRNA level. Thus, OPD reverse P-gp-mediated drug transport via inhibition of P-gp activity and P-gp protein expression as well as downregulation of P-gp mRNA level. Our results suggest that OPD could reverse P-gp-mediated drug resistance in tumor cells.

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Metabolomics analysis of salt tolerance of Zygosaccharomyces rouxii and guided exogenous fatty acid addition for improved salt tolerance

Wang

Huang

et al. 2022

J Sci Food Agric

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BACKGROUND: Zygosaccharomyces rouxii plays an irreplaceable role in the manufacture of traditional fermented foods, which are produced in a high-salt environment. However, there is little research on strategies for improving salt tolerance of Z. rouxii.RESULTS: In this study, metabolomics was used to reveal the changes in intracellular metabolites under salt stress, and the results show that most of the carbohydrate contents decreased, the contents of xanthohumol and glycerol increased (fold change 4.07 and 5.35, respectively), while the contents of galactinol, xylitol and D-threitol decreased (fold change −9.43, −5.83 and −3.59, respectively). In addition, the content of four amino acids and six organic acids decreased, while that of the ten nucleotides increased. Notably, except for stearic acid (C18:0), all fatty acid contents increased. Guided by the metabolomics results, the effect of addition of seven exogenous fatty acids (C12:0, C14:0, C16:0, C18:0, C16:1, C18:1, and C18:2) on the salt tolerance of Z. rouxii was analyzed, and the results suggested that four exogenous fatty acids (C12:0, C16:0, C16:1, and C18:1) can increase the biomass yield and maximum growth rate. Physiological analyses demonstrated that exogenous fatty acids could regulate the distribution of fatty acids in the cell membrane, increase the degree of unsaturation, improve membrane fluidity, and maintain cell integrity, morphology and surface roughness.CONCLUSION: These results are applicable to revealing the metabolic mechanisms of Z. rouxii under salt stress and screening potential protective agents to improve stress resistance by adding exogenous fatty acids.

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Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport

Cited by 19 publications

References 29 publications

Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters

Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters

Reversal Effect of Oxypeucedanin on P-glycoprotein-mediated Drug Transport

Metabolomics analysis of salt tolerance of Zygosaccharomyces rouxii and guided exogenous fatty acid addition for improved salt tolerance

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