摘要
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(3 MOD), 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, 3 MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes NaV1.7, NaV1.8 and NaV1.3 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.
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（3 MOD）, 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, 3 MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes NaV1.7, NaV1.8 and NaV1.3 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.
基金
supported by Ministry of Science and Technology of China(Nos.2013CB911304 and 2014ZX0800949B-002)
the National Natural Science Foundation of China(Nos.U1302221,31372208 and 31630075)
Innovation Programe of Chinese Academy of Sciences(Nos.XDA12020340 and 2015CASEABRI002)
Biological Resources Programme of Chinese Academy of Sciences(No.KFJ-BRP-008)
the Natural Science Foundation of Yunnan Province(Nos.2015BC005,2016FA006 and 2015HA023)
the Natural Science Foundation of Jiangsu Province(Nos.Q0201600440,BE2016742)
