Premium
The natural product argentatin C attenuates postoperative pain via inhibition of voltage‐gated sodium and T‐type voltage‐gated calcium channels
Author(s) -
Duran Paz,
LoyaLópez Santiago,
Ran Dongzhi,
Tang Cheng,
CalderonRivera Aida,
Gomez Kimberly,
Stratton Harrison J.,
Huang Sun,
Xu Yaming,
Wijeratne E. M. Kithsiri,
PerezMiller Samantha,
Shan Zhiming,
Cai Song,
Gabrielsen Anna T.,
Dorame Angie,
Masterson Kyleigh A.,
Alsbiei Omar,
Madura Cynthia L.,
Luo Guoqin,
Moutal Aubin,
Streicher John,
Zamponi Gerald W.,
Gunatilaka A. A. Leslie,
Khanna Rajesh
Publication year - 2023
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15974
Subject(s) - sodium channel , calcium , voltage dependent calcium channel , chemistry , natural product , sodium , t type calcium channel , n type calcium channel , pharmacology , medicine , anesthesia , biochemistry , organic chemistry
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 macaque DRG neurons, and reversed mechanical allodynia in a mouse model of postsurgical pain. 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.