The natural product argentatin C attenuates postoperative pain via inhibition of voltage-gated sodium and T-type voltage-gated calcium channels.
Autor: | Duran P; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA., Loya-López S; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA., Ran D; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Tang C; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA.; NYU Pain Research Center, New York, New York, USA.; Department of Biochemistry and Molecular Biology, College of Life Sciences, Hunan Normal University, Changsha, China., Calderon-Rivera A; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA., Gomez K; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA., Stratton HJ; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Huang S; Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada., Xu YM; Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona, USA., Wijeratne EMK; Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona, USA., Perez-Miller S; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA., Shan Z; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Cai S; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Gabrielsen AT; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Dorame A; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Masterson KA; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Alsbiei O; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Madura CL; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Luo G; Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona, USA., Moutal A; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Streicher J; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, Arizona, USA., Zamponi GW; Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada., Gunatilaka AAL; Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona, USA., Khanna R; Department of Molecular Pathobiology, College of Dentistry, New York University, New York, New York, USA.; NYU Pain Research Center, New York, New York, USA. |
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Jazyk: | angličtina |
Zdroj: | British journal of pharmacology [Br J Pharmacol] 2023 May; Vol. 180 (9), pp. 1267-1285. Date of Electronic Publication: 2023 Jan 15. |
DOI: | 10.1111/bph.15974 |
Abstrakt: | Background and Purpose: Postoperative pain occurs in as many as 70% of surgeries performed worldwide. Postoperative pain management still relies on opioids despite their negative consequences, resulting in a public health crisis. Therefore, it is important to develop alternative therapies to treat chronic pain. Natural products derived from medicinal plants are potential sources of novel biologically active compounds for development of safe analgesics. In this study, we screened a library of natural products to identify small molecules that target the activity of voltage-gated sodium and calcium channels that have important roles in nociceptive sensory processing. Experimental Approach: Fractions derived from the Native American medicinal plant, Parthenium incanum, were assessed using depolarization-evoked calcium influx in rat dorsal root ganglion (DRG) neurons. Further separation of these fractions yielded a cycloartane-type triterpene identified as argentatin C, which was additionally evaluated using whole-cell voltage and current-clamp electrophysiology, and behavioural analysis in a mouse model of postsurgical pain. Key Results: Argentatin C blocked the activity of both voltage-gated sodium and low-voltage-activated (LVA) calcium channels in calcium imaging assays. Docking analysis predicted that argentatin C may bind to Na Conclusion and Implications: These results suggest that the dual effect of argentatin C on voltage-gated sodium and calcium channels supports its potential as a novel treatment for painful conditions. (© 2022 British Pharmacological Society.) |
Databáze: | MEDLINE |
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