The natural product argentatin C attenuates postoperative pain via inhibition of voltage‐gated sodium and T‐type voltage‐gated calcium channels

作者：Paz Duran, Santiago Loya‐López, Dongzhi Ran, Cheng Tang, Aida Calderón‐Rivera, Kimberly Gómez, Harrison J. Stratton, Sun Huang, Ya-Ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez‐Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John M. Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna · 发表于：British Journal of Pharmacology · 年份：2022 · DOI：10.1111/bph.15974 · 被引用次数：18 · 研究领域：Pain Mechanisms and Treatments、Chemical synthesis and alkaloids、Allelopathy and phytotoxic interactions

Abstract 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 V 1.7–1.9 and Ca V 3.1–3.3 channels. Furthermore, argentatin C decreased Na + and T‐type Ca 2+ currents as well as excitability in rat and mac...