Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Na(v)1.7 Voltage-Gated Sodium Channel

Yang, Haoyi1; Shan, Zhiming2,3,4,5; Guo, Weijie1; Wang, Yuwei1; Cai, Shuxian1; Li, Fuyi1; Huang, Qiaojie1; Liu, Jessica Aijia6; Cheung, Chi Wai2; Cai, Song1

2022-12-01

10.3390/ijms232314842

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Impact Factor & Quartile

1422-0067

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 (Na-V) 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) Na-V channels, and (iv) blunts the upregulation of Na(v)1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Na(v)1.7 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.

natural products Narirutin Na(v)1 7 ion channels nociceptive neurons neuropathic pain

SCI

English

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Biochemistry & Molecular Biology ; Chemistry

Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary

WOS:000896129100001

MDPI

CHEMISTRY

Web of Science

1.Shenzhen Univ, Dept Anat & Histol, Hlth Sci Ctr, Shenzhen 518060, Peoples R China
2.Univ Hong Kong, Lab & Clin Res Inst Pain, Li Ka Shing Fac Med, Sch Clin Med,Dept Anaesthesiol, Hong Kong 999077, Peoples R China
3.Southern Univ Sci & Technol, Dept Anethesiol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
4.Jinan Univ, Clin Med Coll 2, Shenzhen 518020, Peoples R China
5.Shenzhen Engn Res Ctr Anesthesiol, Shenzhen 518020, Peoples R China
6.City Univ Hong Kong, Dept Neurosci, Hong Kong 999077, Peoples R China

Yang, Haoyi,Shan, Zhiming,Guo, Weijie,et al. Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Na(v)1.7 Voltage-Gated Sodium Channel[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2022,23(23).

Yang, Haoyi.,Shan, Zhiming.,Guo, Weijie.,Wang, Yuwei.,Cai, Shuxian.,...&Cai, Song.(2022).Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Na(v)1.7 Voltage-Gated Sodium Channel.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,23(23).

Yang, Haoyi,et al."Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Na(v)1.7 Voltage-Gated Sodium Channel".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23.23(2022).