Inhibitory effects of astilbin, neoastilbin and isoastilbin on human cytochrome CYP3A4 and 2D6 activities

Shi, Yurui; Xie, Jing; Chen, Rongda; Liu, Guiming; Tao, Yanzhou; Fan, Yangyang; Wang, Xiaolin; Xu, Jiaming

doi:10.1002/bmc.5039

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…According to multiple spectroscopic coupled with molecular docking analysis, astilbin has strong binding ability to human CYP2D6 ( Tao et al, 2021 ). Ultrahigh-performance liquid chromatography and triple quadrupole mass spectrometry have been used to confirm the interaction of human CYP3A4 and CYP2D6 with astilbin ( Shi et al, 2021 ). In the present study, astilbin efficiently stimulated the ROS of human CD4 + T cells, indicating the inhibition of CYP3A4 and CYP2D6 by astilbin.…”

Section: Discussionmentioning

confidence: 99%

Astilbin Activates the Reactive Oxidative Species/PPARγ Pathway to Suppress Effector CD4+ T Cell Activities via Direct Binding With Cytochrome P450 1B1

Ding

Wang

et al. 2022

Front. Pharmacol.

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Astilbin, as a compound of flavonoids, exerts anti-inflammation, antioxidation, and immune-suppression activities. Decreased activation of NF-κB and p38 MAPK and increased activation of SOCS3 and AMPK have been found in astilbin-treated cells. However, what molecules are docked by astilbin to initiate signaling cascades and result in functional changes remains unknown. In the study, we found that astilbin efficiently suppressed TNF-α production and increased CCR9 and CD36 expression of CD4+ T cells. In vivo administration of astilbin repressed the occurrence of type 1 diabetes mellitus in non-obese diabetic mice. The PPARγ/SOCS3, PPARγ/PTEN, and PPARγ/AMPK signaling pathways were substantially activated and played key roles in astilbin-induced downregulation of CD4+ T cell functions. Transcriptome sequencing results confirmed the changes of signaling molecules involved in the immune system, inflammatory responses, and indicated variations of multiple enzymes with oxidant or antioxidant activities. Astilbin directly induced cytoplasmic ROS production of CD4+ T cells ex vivo, but had no effects on mitochondrial ROS and mitochondrial weight. When cellular ROS was depleted, astilbin-treated CD4+ T cells remarkably reversed the expression of TNF-α, IFN-γ, CCR9, CD36, and signaling molecules (PPARγ, PTEN, p-AMPK, and SOCS3). Based on bioinformatics, two P450 enzymes (CYP1B1 and CYP19A1) were selected as candidate receptors for astilbin. CYP1B1 was identified as a real docking protein of astilbin in ROS production by AutoDock Vina software analysis and surface plasmon resonance assay. Collectively, astilbin downregulates effector CD4+ T cell activities via the CYP1B1/ROS/PPARγ pathway, which firmly supports its potential use in the treatment of inflammation.

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Section: Discussionmentioning

confidence: 99%

Astilbin Activates the Reactive Oxidative Species/PPARγ Pathway to Suppress Effector CD4+ T Cell Activities via Direct Binding With Cytochrome P450 1B1

Ding

Wang

et al. 2022

Front. Pharmacol.

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“…Radical scavening(%) = A control − A sample /A sample × 100 (10) where A control is the absorbance of DPPH alone and A sample is the absorbance of DPPH with astilbin in the presence or absence of HSA.…”

Section: Effect Of Hsa On the Antioxidant Capacity Of Astilbinmentioning

confidence: 99%

“…Noteworthily, wines contain high levels of astilbin [ 7 ], which has been shown to contribute notably to the sweet taste of dry wines [ 8 ]. Modern pharmacological studies have shown that astilbin has various pharmacological activities such as anti-inflammatory [ 9 ], immunosuppressive [ 10 ], antioxidant [ 11 ], anti-diabetic [ 12 ] and cardiovascular protection [ 13 ]. Overall observations from data suggested that astilbin is a promising compound and a “star material” for the development of new health food products.…”

Section: Introductionmentioning

confidence: 99%

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

et al. 2022

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Astilbin is a dihydroflavonol glycoside identified in many natural plants and functional food with promising biological activities which is used as an antioxidant in the pharmaceutical and food fields. This work investigated the interaction between astilbin and human serum albumin (HSA) and their effects on the antioxidant activity of astilbin by multi-spectroscopic and molecular modeling studies. The experimental results show that astilbin quenches the fluorescence emission of HSA through a static quenching mechanism. Astilbin and HSA prefer to bind at the Site Ⅰ position, which is mainly maintained by electrostatic force, hydrophobic and hydrogen bonding interactions. Multi-spectroscopic and MD results indicate that the secondary structure of HSA could be changed because of the interaction of astilbin with HSA. DPPH radical scavenging assay shows that the presence of HSA reduces the antioxidant capacity of astilbin. The explication of astilbin–HSA binding mechanism will provide insights into clinical use and resource development of astilbin in food and pharmaceutical industries.

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Comparative study of the interaction mechanism of astilbin, isoastilbin, and neoastilbin with CYP3A4

Tao,

Fan,

Wang

et al. 2023

Luminescence

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The interactions of human CYP3A4 with three selected isomer flavonoids, such as astilbin, isoastilbin and neoastilbin, were clarified using spectral analysis, molecular docking, and molecular dynamics simulation. During binding with the three flavonoids, the intrinsic fluorescence of CYP3A4 was statically quenched in static mode with nonradiative energy conversion. The fluorescence and ultraviolet/visible (UV/vis) data revealed that the three flavonoids had a moderate and stronger binding affinity with CYP3A4 due to the order of the Ka1 and Ka2 values ranging from 104 to 105 L·mol−1. In addition, astilbin had the highest affinity with CYP3A4, then isoastilbin and neoastilbin, at the three experimental temperatures. Multispectral analysis confirmed that binding of the three flavonoids resulted in clear changes in the secondary structure of CYP3A4. It was found from fluorescence, UV/vis and molecular docking analyses that these three flavonoids strongly bound to CYP3A4 by means of hydrogen bonds and van der Waals forces. The key amino acids around the binding site were also elucidated. Furthermore, the stabilities of the three CYP3A4 complexes were evaluated using molecular dynamics simulation.

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Inhibitory effects of astilbin, neoastilbin and isoastilbin on human cytochrome CYP3A4 and 2D6 activities

Cited by 4 publications

References 22 publications

Astilbin Activates the Reactive Oxidative Species/PPARγ Pathway to Suppress Effector CD4+ T Cell Activities via Direct Binding With Cytochrome P450 1B1

Astilbin Activates the Reactive Oxidative Species/PPARγ Pathway to Suppress Effector CD4+ T Cell Activities via Direct Binding With Cytochrome P450 1B1

Molecular Insight into the Binding of Astilbin with Human Serum Albumin and Its Effect on Antioxidant Characteristics of Astilbin

Comparative study of the interaction mechanism of astilbin, isoastilbin, and neoastilbin with CYP3A4

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