Publications by authors named "Xiang-Yan Wei"

5 Publications

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Alteration of twinfilin1 expression underlies opioid withdrawal-induced remodeling of actin cytoskeleton at synapses and formation of aversive memory.

Mol Psychiatry 2021 May 7. Epub 2021 May 7.

Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Exposure to drugs of abuse induces alterations of dendritic spine morphology and density that has been proposed to be a cellular basis of long-lasting addictive memory and heavily depend on remodeling of its underlying actin cytoskeleton by the actin cytoskeleton regulators. However, the actin cytoskeleton regulators involved and the specific mechanisms whereby drugs of abuse alter their expression or function are largely unknown. Twinfilin (Twf1) is a highly conserved actin-depolymerizing factor that regulates actin dynamics in organisms from yeast to mammals. Despite abundant expression of Twf1 in mammalian brain, little is known about its importance for brain functions such as experience-dependent synaptic and behavioral plasticity. Here we show that conditioned morphine withdrawal (CMW)-induced synaptic structure and behavior plasticity depends on downregulation of Twf1 in the amygdala of rats. Genetically manipulating Twf1 expression in the amygdala bidirectionally regulates CMW-induced changes in actin polymerization, spine density and behavior. We further demonstrate that downregulation of Twf1 is due to upregulation of miR101a expression via a previously unrecognized mechanism involving CMW-induced increases in miR101a nuclear processing via phosphorylation of MeCP at Ser421. Our findings establish the importance of Twf1 in regulating opioid-induced synaptic and behavioral plasticity and demonstrate its value as a potential therapeutic target for the treatment of opioid addiction.
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http://dx.doi.org/10.1038/s41380-021-01111-3DOI Listing
May 2021

Discovery and characterization of flavonoids in vine tea as catechol-O-methyltransferase inhibitors.

Fitoterapia 2021 Apr 28;152:104913. Epub 2021 Apr 28.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Vine tea has been used as a traditionally functional herbal tea in China for centuries, which exhibits paramount potential for chronic metabolic diseases. Herein, the inhibitory potential of vine tea toward human catechol-O-methyltransferase (hCOMT) was investigated. A practical bioactivity-guided fractionation combined with chemical profiling strategy was developed to identify the naturally occurring hCOMT inhibitors. Five flavonoids in vine tea displayed moderate to strong inhibition on hCOMT with IC values ranging from 0.96 μM to 42.47 μM, in which myricetin was the critically potent constituent against hCOMT. Inhibition kinetics assays and molecular docking simulations showed that myricetin could bind to the active site of COMT and inhibited COMT-catalyzed 3-BTD methylation in a mixed manner. Collectively, our findings not only suggested that the strong hCOMT inhibition of vine tea has guiding significance in the drug exposure of catechol drugs, but also identified a promising lead compound for developing more efficacious hCOMT inhibitors.
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http://dx.doi.org/10.1016/j.fitote.2021.104913DOI Listing
April 2021

Herb-drug interaction between Styrax and warfarin: Molecular basis and mechanism.

Phytomedicine 2020 Oct 21;77:153287. Epub 2020 Jul 21.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200473, China. Electronic address:

Background: Styrax, one of the most famous folk medicines, has been frequently used for the treatment of cardiovascular diseases and skin problems in Asia and Africa. It is unclear whether Styrax or Styrax-related herbal medicines may trigger clinically relevant herb-drug interactions.

Purpose: This study was carried out to investigate the inhibitory effects of Styrax on human cytochrome P450 enzymes (CYPs) and to clarify whether this herb may modulate the pharmacokinetic behavior of the CYP-substrate drug warfarin when co-administered.

Study Design: The inhibitory effects of Styrax on CYPs were assayed in human liver microsomes (HLM), while the pharmacokinetic interactions between Styrax and warfarin were investigated in rats. The bioactive constituents in Styrax with strong CYP3A inhibitory activity were identified and their inhibitory mechanisms were carefully investigated.

Methods: The inhibitory effects of Styrax on human CYPs were assayed in vitro, while the pharmacokinetic interactions between Styrax and warfarin were studied in rats. Fingerprinting analysis of Styrax coupled with LC-TOF-MS/MS profiling and CYP inhibition assays were used to identify the constituents with strong CYP3A inhibitory activity. The inhibitory mechanism of oleanonic acid (the most potent CYP3A inhibitor occurring in Styrax) against CYP3A4 was investigated by a panel of inhibition kinetics analyses and in silico analysis.

Results: In vitro assays demonstrated that Styrax extract strongly inhibited human CYP3A and moderately inhibited six other tested human CYPs, as well as potently inhibited warfarin 10-hydroxylation in liver microsomes from both humans and rats. In vivo assays demonstrated that compared with warfarin given individually in rats, Styrax (100 mg/kg) significantly prolonged the plasma half-life of warfarin by 2.3-fold and increased the AUC of warfarin by 2.7-fold when this herb was co-administrated with warfarin (2 mg/kg) in rats. Two LC fractions were found with strong CYP3A inhibitory activity and the major constituents in these fractions were characterized by LC-TOF-MS/MS. Five pentacyclic triterpenoid acids (including epibetulinic acid, betulinic acid, betulonic acid, oleanonic acid and maslinic acid) present in Styrax were potent CYP3A inhibitors, and oleanonic acid was a competitive inhibitor against CYP3A-mediated testosterone 6β-hydroxylation.

Conclusion: Styrax and the pentacyclic triterpenoid acids occurring in this herb strongly modulate the pharmacokinetic behavior of warfarin via inhibition of CYP3A.
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http://dx.doi.org/10.1016/j.phymed.2020.153287DOI Listing
October 2020

A near-infrared Nile red fluorescent probe for the discrimination of biothiols by dual-channel response and its bioimaging applications in living cells and animals.

Analyst 2019 Jun 14;144(11):3676-3684. Epub 2019 May 14.

Experiment Center of Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Biothiols, including cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and HS, play important roles in human physiological processes. However, it is a great difficulty to distinguish biothiols from each other because of their similar chemical properties. Based on Nile red, we have designed and synthesized a near-infrared fluorescent probe for discriminating Cys/Hcy from GSH/HS by a dual-channel detection method. Using an ether bond, near-infrared Nile red was attached to 7-nitrobenzofurazan to construct the probe. Due to the photo-induced electron transfer, the probe showed almost no fluorescence from the green to red emission band. But upon the addition of Cys (0-150 μM) or Hcy (0-200 μM), the probe exhibited a noteworthy fluorescence "turn-on" signal in two unique emission bands (Green and Red) with a fast response (within 30 min). In contrast, the probe displayed an increase in fluorescence only in the red channel when encountering GSH (0-70 μM) or HS (0-50 μM), and GSH/HS could be tested respectively by different response time. The limit of detection was calculated to be 0.09 μM (Cys), 0.30 μM (Hcy), 0.24 μM (GSH), and 0.04 μM (HS), respectively (based on S/N = 3). The desirable dual-channel detection could be achieved in serum samples and living cells. Moreover, the probe could be applied for bioimaging in mice, which indicated its potential application in the clinic.
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http://dx.doi.org/10.1039/c9an00280dDOI Listing
June 2019

[Influences of the introduction of western medicine on the evolution of concept of viscera-bowels theory].

Zhonghua Yi Shi Za Zhi 2013 Nov;43(6):351-5

Affiliated Zhongshan Hospital of Fudan University, Shanghai, 201203, China.

Viscera-bowels theory is one of the key parts of the theoretical system of traditional Chinese medicine (TCM). The concept of viscera-bowels in TCM at the turn of the Ming-Qing Dynasties must have anatomical significance in western medical context. By then, western medicine began its dissemination into China with the conflict between it and TCM, which gradually increased, and eventually triggering the major debate between them in early 20th century. Under this background, Yun Tie-qiao definitely pointed out that TCM viscera-bowels was different from western anatomical visceral organs; rather, it was a theoretical model characterized by seasonal qi transformation. Thus, it became the beginning of the nature of five viscera - six bowels interpreted by TCM functional unit and pushing the development of modern TCM theoretical system. Hence, the correct handling of history of its evolutionary process from the TCM recognition on viscera-bowels to the western visceral idea is helpful to the orientation and its total implication in TCM viscera-bowels and its research.
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November 2013