Kaempferol modulates TCDD- and <i>t</i>-BHQ-induced drug-metabolizing enzymes and luteolin enhances this effect

Kitakaze, Tomoya; Makiyama, Atsushi; Nakai, Rika; Kimura, Yûki; Ashida, Hitoshi

doi:10.1039/c9fo02951f

Cited by 9 publications

(9 citation statements)

References 42 publications

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“…The cells were harvested with PBS and centrifuged at 800 g for 5 min at 4 °C. After the resultant precipitate was treated with the deconjugation enzymes (β-glucuronidase and sulfatase), kaempferol was extracted from the cells and quantified by HPLC as described in the previous report …”

Section: Materials and Methodsmentioning

confidence: 99%

“…After the resultant precipitate was treated with the deconjugation enzymes (β-glucuronidase and sulfatase), kaempferol was extracted from the cells and quantified by HPLC as described in the previous report. 27 Statistical Analysis. All data are represented as the mean ± standard deviation (SD) from the results of at least three independent determinations.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway

Kitakaze

Jiang

Nomura

et al. 2020

J. Agric. Food Chem.

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Kaempferol possesses various health-promoting functions including antihyperglycemic activity, but its underlying molecular mechanism is poorly understood. Glucose transporter 4 (GLUT4) plays an important role in the uptake of blood glucose into muscle cells after its translocation to the plasma membrane. In this study, we demonstrated that kaempferol at 1.0 nM or more significantly increased the uptake of 2-[3H]- deoxy-d-glucose by 1.3–1.4-fold in L6 myotubes. Kaempferol at 10 pM or more also significantly increased GLUT4 translocation by 1.3–1.6-fold. Kaempferol at 1.0 nM significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) by 2.9-fold, liver kinase B1 and Janus kinase 2 (JAK2) by 1.9-fold, and signal transducer and activator of transcription 3 by 3.7-fold. In addition, kaempferol increased phosphorylation of phosphoinositide 3-kinase (PI3K) by 1.8-fold but not the insulin receptor. Small interfering RNA (siRNA) for AMPK, JAK2, or PI3K canceled kaempferol-induced glucose uptake and GLUT4 translocation. Furthermore, siRNA for JAK2 canceled kaempferol-induced phosphorylation of AMPK and PI3K. These results indicate that a JAK2-depdendent pathway regulates kaempferol-induced glucose uptake and GLUT4 translocation in L6 myotubes and that kaempferol may be an effective compound for the prevention of hyperglycemia.

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Section: Materials and Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway

Kitakaze

Jiang

Nomura

et al. 2020

J. Agric. Food Chem.

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“…[24][25][26] Luteolin enhances the kaempferol-inhibited expression of drug-metabolizing enzymes, and co-treatment with kaempferol and luteolin was previously found to increase the cellular levels of kaempferol without affecting the levels of luteolin. [27] Quercetin can inhibit the activation of P38, ERK1/2, and NF-κB; reduce the expression of cyclooxygenase and lipoxygenase; maintain the stability of mast cells; reduce the production of IL-1β, IL-6, and TNFα; inhibit Lyn/PLCγ/IP3R-Ca 2+ , Lyn/ERK1/2, and Lyn/NF-κB signaling pathways; and achieve anti-inflammatory effects. [28][29][30] Naringin can reduce the release of IL-1β, IL-6, and IL-18 and inhibit the high expression of NF-κB-P65.…”

Section: Discussionmentioning

confidence: 99%

Identification of the key mechanisms of action of Si-Ni-San in uveitis using bioinformatics and network pharmacology

Zhang,

Hong,

Zhang

et al. 2023

Medicine

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Background: Uveitis is an eye disease with a high rate of blindness, whose pathogenesis is not completely understood. Si-Ni-San (SNS) has been used as a traditional medicine to treat uveitis in China. However, its mechanism of action remains unclear. This study explored the potential mechanisms of SNS in the treatment of uveitis through network pharmacology and bioinformatics. Methods: Using R language and Perl software, the active components and predicted targets of SNS, as well as the related gene targets of uveitis, were mined through the Traditional Chinese Medicine Systems Pharmacology, Therapeutic Target, Gene Expression Omnibus, GeneCards, and DrugBank databases. The network diagram of active components and intersection targets was constructed using Cytoscape software and the String database. The CytoNCA plug-in was used to conduct topological analysis on the network diagram and screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Chemoffice, Pymol, AutoDock, and Vina were used to analyze the molecular docking of key targets and core compounds of diseases through the PubChem database. Results: JUN, RELA, and MAPK may play important roles in the treatment of uveitis by SNS. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that core genes were mainly concentrated in MAPK, toll-like receptor, tumor necrosis factor, and nucleotide oligomerization domain-like receptor signaling pathways. In addition, molecular docking results showed that the bioactive compounds (kaempferol, luteolin, naringin, and quercetin) exhibited good binding ability to JUN, RELA, and MAPK. Conclusion: Based on these findings, SNS exhibits multi-component and multi-target synergistic action in the treatment of uveitis, and its mechanism may be related to anti-inflammatory and immune regulation.

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“…After calculating the binding energy value (KJ/mol) and analyzing the docking effect of 64 groups in Table S2 , different flavonoids showed conservative or similar binding conformations across the active site of the same receptor, indicating that similar physiological activities of flavonoids were closely related to their highly homologous structures [ 91 , 92 ]. For instance, co-treatment with luteolin (A18) and kaempferol (C17) enhances the inhibitory effect on the expression of drug-metabolizing enzymes [ 93 ]. This unique material foundation can reasonably strengthen the compatibility effect.…”

Section: Discussionmentioning

confidence: 99%

Systems pharmacology-based drug discovery and active mechanism of natural products for coronavirus pneumonia (COVID-19): An example using flavonoids

Wang

Ding

Zhao

et al. 2022

Computers in Biology and Medicine

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Kaempferol modulates TCDD- and t-BHQ-induced drug-metabolizing enzymes and luteolin enhances this effect

Abstract: Co-treatment with kaempferol and luteolin inhibits AhR- and Nrf2-induced expression of drug-metabolizing enzymes.

Cited by 9 publications

References 42 publications

Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway

Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway

Identification of the key mechanisms of action of Si-Ni-San in uveitis using bioinformatics and network pharmacology

Systems pharmacology-based drug discovery and active mechanism of natural products for coronavirus pneumonia (COVID-19): An example using flavonoids

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