دورية أكاديمية
Icariside II, a Prenyl-Flavonol, Alleviates Inflammatory and Neuropathic Pain by Inhibiting T-Type Calcium Channels and USP5-Cav3.2 Interactions.
| العنوان: | Icariside II, a Prenyl-Flavonol, Alleviates Inflammatory and Neuropathic Pain by Inhibiting T-Type Calcium Channels and USP5-Cav3.2 Interactions. |
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| المؤلفون: | Ali MY; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada.; Zymedyne Therapeutics, Calgary, AB T2N4G4, Canada., Gadotti VM; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada.; Zymedyne Therapeutics, Calgary, AB T2N4G4, Canada., Huang S; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada., Garcia-Caballero A; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada.; Zymedyne Therapeutics, Calgary, AB T2N4G4, Canada., Antunes FTT; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada., Jung HA; Department of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, Republic of Korea., Choi JS; Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea., Zamponi GW; Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N4N1, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada. |
| المصدر: | ACS chemical neuroscience [ACS Chem Neurosci] 2023 May 17; Vol. 14 (10), pp. 1859-1869. Date of Electronic Publication: 2023 Apr 28. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society |
| مواضيع طبية MeSH: | Calcium Channels, T-Type*/metabolism , Neuralgia*/drug therapy , Neuralgia*/metabolism, Female ; Mice ; Animals ; Molecular Docking Simulation ; Hyperalgesia/metabolism ; Flavonoids ; Flavonols ; Mice, Knockout ; Ubiquitin-Specific Proteases/metabolism |
| مستخلص: | Cav3.2 channels play an important role in the afferent nociceptive pathway, which is responsible for both physiological and pathological pain transmission. Cav3.2 channels are upregulated during neuropathic pain or peripheral inflammation in part due to an increased association with the deubiquitinase USP5. In this study, we investigated nine naturally occurring flavonoid derivatives which we tested for their abilities to inhibit transiently expressed Cav3.2 channels and their interactions with USP5. Icariside II (ICA-II), one of the flavonols studied, inhibited the biochemical interactions between USP5 and Cav3.2 and concomitantly and effectively blocked Cav3.2 channels. Molecular docking analysis predicts that ICA-II binds to the cUBP domain and the Cav3.2 interaction region. In addition, ICA-II was predicted to interact with residues in close proximity to the Cav3.2 channel's fenestrations, thus accounting for the observed blocking activity. In mice with inflammatory and neuropathic pain, ICA-II inhibited both phases of the formalin-induced nocifensive responses and abolished thermal hyperalgesia induced by injection of complete Freund's adjuvant (CFA) into the hind paw. Furthermore, ICA-II produced significant and long-lasting thermal anti-hyperalgesia in female mice, whereas Cav3.2 null mice were resistant to the action of ICA-II. Altogether, our data show that ICA-II has analgesic activity via an action on Cav3.2 channels. |
| فهرسة مساهمة: | Keywords: Cav3.2 III−IV linker; Cav3.2 T-type channel; Icariside II; USP5; flavonoids; molecular docking; pain |
| المشرفين على المادة: | 0 (Calcium Channels, T-Type) 113558-15-9 (baohuoside I) 0 (prenyl) 0 (Flavonoids) 0 (Flavonols) EC 3.4.19.12 (Usp5 protein, mouse) EC 3.4.19.12 (Ubiquitin-Specific Proteases) |
| تواريخ الأحداث: | Date Created: 20230428 Date Completed: 20230518 Latest Revision: 20230524 |
| رمز التحديث: | 20230525 |
| DOI: | 10.1021/acschemneuro.3c00083 |
| PMID: | 37116219 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1948-7193 |
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| DOI: | 10.1021/acschemneuro.3c00083 |