Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Nav1.7 Voltage-Gated Sodium Channel
-
Published:2022-11-27
Issue:23
Volume:23
Page:14842
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Yang Haoyi, Shan ZhimingORCID, Guo Weijie, Wang Yuwei, Cai Shuxian, Li Fuyi, Huang Qiaojie, Liu Jessica Aijia, Cheung Chi Wai, Cai SongORCID
Abstract
Neuropathic pain is a refractory chronic disease affecting millions of people worldwide. Given that present painkillers have poor efficacy or severe side effects, developing novel analgesics is badly needed. The multiplex structure of active ingredients isolated from natural products provides a new source for phytochemical compound synthesis. Here, we identified a natural product, Narirutin, a flavonoid compound isolated from the Citrus unshiu, showing antinociceptive effects in rodent models of neuropathic pain. Using calcium imaging, whole-cell electrophysiology, western blotting, and immunofluorescence, we uncovered a molecular target for Narirutin’s antinociceptive actions. We found that Narirutin (i) inhibits Veratridine-triggered nociceptor activities in L4-L6 rat dorsal root ganglion (DRG) neurons, (ii) blocks voltage-gated sodium (NaV) channels subtype 1.7 in both small-diameter DRG nociceptive neurons and human embryonic kidney (HEK) 293 cell line, (iii) does not affect tetrodotoxin-resistant (TTX-R) NaV channels, and (iv) blunts the upregulation of Nav1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Nav1.7 as a molecular target of Narirutin may further clarify the analgesic mechanism of natural flavonoid compounds and provide an optimal idea to produce novel selective and efficient analgesic drugs.
Funder
National Natural Science Foundation of China Science and Technology Planning Project of Shenzhen Shenzhen Key Medical Discipline Construction Fund Sanming Project of Medicine in Shenzhen
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference47 articles.
1. A new definition of neuropathic pain;Jensen;Pain,2011 2. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients with Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial;Krebs;JAMA,2018 3. Opioid agonist treatment for people who are dependent on pharmaceutical opioids;Nielsen;Cochrane Database Syst. Rev.,2022 4. Khan, F.A., Ali, G., Rahman, K., Khan, Y., Ayaz, M., Mosa, O.F., Nawaz, A., Hassan, S.S.U., and Bungau, S. (2022). Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms. Molecules, 27. 5. Khatoon, F., Ali, S., Kumar, V., Elasbali, A.M., Alhassan, H.H., Alharethi, S.H., Islam, A., and Hassan, M.I. (2022). Pharmacological features, health benefits and clinical implications of honokiol. J. Biomol. Struct. Dyn., 1–23.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|