3'-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels

Run-Jia Xu; Shuo-Han Fei; Lin-Yan Chen; Gan Wang; Ming Liu; Wen-Sheng Zhang; Xiu-Wen Yan; Ren Lai; Chuan-Bin Shen

doi:10.1016/S1875-5364(19)30049-4

3'-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels

Chin J Nat Med. 2019 Jun;17(6):413-423. doi: 10.1016/S1875-5364(19)30049-4.

Authors

Run-Jia Xu¹, Shuo-Han Fei¹, Lin-Yan Chen¹, Gan Wang², Ming Liu³, Wen-Sheng Zhang⁴, Xiu-Wen Yan¹, Ren Lai⁵, Chuan-Bin Shen⁶

Affiliations

¹ Life Sciences College of Nanjing Agricultural University, Nanjing 210095, China.
² Key Laboratory of bioactive peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, China.
³ Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
⁴ Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ Life Sciences College of Nanjing Agricultural University, Nanjing 210095, China; Key Laboratory of bioactive peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, China; Sino-African Joint Research Center, CAS, Kunming Institute of Zoology, Kunming 650223, China. Electronic address: rlai@mail.kiz.ac.cn.
⁶ Key Laboratory of bioactive peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming 650223, China. Electronic address: shenchuanbin@mail.kiz.ac.cn.

PMID: 31262454
DOI: 10.1016/S1875-5364(19)30049-4

Abstract

Isoflavones are widely consumed by people around the world in the form of soy products, dietary supplements and drugs. Many isoflavones or related crude extracts have been reported to exert pain-relief activities, but the mechanism remains unclear. Voltage-gated sodium channels (VGSCs) play important roles in excitability of pain sensing neurons and many of them are important nociceptors. Here, we report that several isoflavones including 3'-methoxydaidzein (3MOD), genistein (GEN) and daidzein (DAI) show abilities to block VGSCs and thus to attenuate chemicals and heat induced acute pain or chronic constriction injury (CCI) induced pain hypersensitivity in mice. Especially, 3MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes Na_V1.7, Na_V1.8 and Na_V1.3 with the IC₅₀ of 181 ± 14, 397 ± 26, and 505 ± 46 nmol·L^-1, respectively, providing a promising compound or parent structure for the treatment of pain pathologies. This study reveals a pain-alleviating mechanism of dietary isoflavones and may provide a convenient avenue to alleviate pain.

Keywords: 3′-Methoxydaidzein; Analgesic; Chronic pain; Isoflavone; Sodium channel.

MeSH terms

Analgesics / administration & dosage*
Analgesics / chemistry
Animals
Humans
Isoflavones / administration & dosage*
Isoflavones / chemistry
Male
Mice
Mice, Inbred C57BL
Pain / drug therapy*
Pain / genetics
Pain / metabolism
Voltage-Gated Sodium Channel Blockers / administration & dosage*
Voltage-Gated Sodium Channels / genetics
Voltage-Gated Sodium Channels / metabolism*

Substances

Analgesics
Isoflavones
Voltage-Gated Sodium Channel Blockers
Voltage-Gated Sodium Channels
daidzein