Resveratrol Derivatives Inhibit Transthyretin Fibrillization: Structural Insights into the Interactions between Resveratrol Derivatives and Transthyretin

Q1 · MEDICINE

Article

Author: Yokoyama, Takeshi ; Mizuguchi, Mineyuki ; Fujiwara, Satoru ; Nabeshima, Yuko ; Kusaka, Katsuhiro

Hereditary ATTR amyloidosis is a disease caused by the deposition of amyloid fibrils formed by mutated transthyretin (TTR), a protein that binds to thyroid hormone in the serum, in the organs. The development of a small molecule that binds to and stabilizes TTR is a promising strategy for the treatment of ATTR amyloidosis. In the present study, we demonstrated that the resveratrol derivatives including pterostilbene available as a dietary supplement inhibit the fibrillization of V30M-TTR to the same extent as the approved drug tafamidis. Furthermore, based on a thermodynamic and X-ray crystallographic analysis, the binding of the resveratrol derivative to TTR was shown to be enthalpy-driven, with the binding enthalpy being acquired by hydrogen bonding to S117. Moreover, direct observation of hydrogen atoms by neutron crystallography provided details of the hydrogen bond network by S117 and emphasized the importance of the CH···π interaction by L110 in the ligand binding.

01 Oct 2023·Molecular nutrition & food research

Retracted: Resveratrol Derivative, Trans-3, 5, 4'-Trimethoxystilbene, Prevents the Developing of Atherosclerotic Lesions and Attenuates Cholesterol Accumulation in Macrophage Foam Cells.

Author: Hong, Ming ; Li, Siying ; Li, Jinke ; Almutairi, Mohammed M

Mol. Nutr. Food Res.2020, 64, 1 901 115 https://doi.org/10.1002/mnfr.201901115. The above article, published online on 22 January 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal's Editor-in-Chief, Dr. Julia Reuter, and Wiley-VCH GmbH. Following publication, the journal was contacted by the University of Kansas who indicated that three of the co-authors, Jinke Li, Siying Li and Mohammed M. Almutairi, whose affiliations had been noted at the Department of Pharmacology & Toxicology, University of Kansas, were not affiliated with the university. In addition, the journal was made aware of concerns raised by third parties regarding this article which evidences image duplication between Figures 1, 2, 3, 4, 6, and 7, and Table 1 in this article and two other articles purporting to show different data. The authors were contacted to ask for their explanation of the concerns raised, but no response was received. The retraction has been agreed as the editorial team no longer have confidence in the reported results and conclusions given the significant overlap between the results reported in the Figures and other published articles.

01 Apr 2023·Inflammation

Radial Extracorporeal Shock Wave Therapy Combined with Resveratrol Derivative Alleviates Chronic Nonbacterial Prostatitis in Rats

Article

Author: Jin, Chen ; Bian, Zichen ; Song, Zhengyao ; Liang, Chaozhao

Resveratrol (Res) is a non-flavonoid polyphenol compound with biological pleiotropic properties, but low bioavailability limits its application value. Here, we synthesized a new Res derivative ((E)-5-(dimethylamino)-2-(4-methoxystyryl)phenol), and attempted to determine the function of Res derivative combined with radial extracorporeal shock wave therapy (rESWT) in chronic nonbacterial prostatitis (CNP). CNP model rats were constructed by subcutaneous administration of prostatein suspension (15 mg/ml), followed by rESWT treatment alone or in associated with Res or Res derivatives. In this study, inflammatory cell infiltration and tissue fibrosis in the prostate tissues of CNP rats were significantly deteriorated, which was effectively abolished by rESWT treatment alone or in combination with Res or Res derivative. The expression of interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), and nuclear factor kappa-B (NF-κB) were increased, while silent information regulator 1 (SIRT1) expression was suppressed in the prostate tissues of CNP rats, which were then rescued by rESWT treatment alone or in associated with Res or Res derivative. Importantly, compared with Res derivative treatment alone or rESWT combined with Res treatment, combination treatment with rESWT and Res derivative was more effective in alleviating inflammation and fibrosis, in reducing IL-1β, TNF-α, NGF, and SIRT1 expression, and in facilitating SIRT1 expression. Overall, rESWT combined with Res derivative treatment improved CNP in rat by reducing inflammation and fibrosis, which attributed to regulate the expression of SIRT1 and NF-κB. Thus, this work provides a theoretical basis for rESWT combined with Res derivative in the clinical treatment of CNP.

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Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipidemias	Discovery	CN	Academy of Military Med Sci, Inst of Toxicology & Pharmacology	-

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