Interaction study of astilbin, isoastilbin and neoastilbin toward CYP2D6 by multi‐spectroscopy and molecular docking

The interaction mechanism of pelargonidin (PG) with tyrosinase was investigated by multi-spectroscopy and molecular docking. As a result, PG had strong inhibitory activity on tyrosinase with the IC 50 value of 41.94 Â 10 À6 molÁL À1 . The inhibition type of PG against tyrosinase was determined as a mixed-mode. Meanwhile, the fluorescence of tyrosinase was quenched statically by PG, and accompanied by non-radiative energy transfer. The three-dimensional (3-D) fluorescence, ultravioletvisible spectroscopy (UV-Vis) and circular dichroism spectroscopies (CD) indicated that PG decreased the hydrophobicity of the micro-environment around tryptophan (Trp) and tyrosine (Tyr), which resulted in the conformational change of tyrosinase. In addition, fluorescence and molecular docking analysis indicated that PG bound to tyrosinase via hydrogen bonds (H-bonds) and van der Waals force (vdW force). We herein recommended that PG might be a potential candidate drug for the treatment of melanin-related diseases.

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“…The energy transfer efficiency was obtained according to Equations (). 35,36

E goodbreak= 1 goodbreak- ((), \frac{F}{F_{0}}) goodbreak= \frac{R_{0}^{6}}{R_{0}^{6} + r^{6}}

R_{0}^{6} goodbreak= 8.8 goodbreak\times 10^{- 25} K^{2} N^{- 4} φ normalJ

J goodbreak= \frac{F ((), λ) ε ((), λ) λ^{4} normalΔ λ}{\sum F ((), λ) normalΔ λ}

…”

Section: Methodsmentioning

confidence: 99%

Interaction mechanism of pelargonidin against tyrosinase by multi‐spectroscopy and molecular docking

Tao

Chen

Fan

et al. 2022

J of Molecular Recognition

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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 ).…”

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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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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Interaction study of astilbin, isoastilbin and neoastilbin toward CYP2D6 by multi‐spectroscopy and molecular docking

Cited by 3 publications

References 41 publications

Interaction mechanism of pelargonidin against tyrosinase by multi‐spectroscopy and molecular docking

Interaction mechanism of pelargonidin against tyrosinase by multi‐spectroscopy and molecular docking

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

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

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