Journal
PHYTOTHERAPY RESEARCH
Volume 33, Issue 3, Pages 718-727Publisher
WILEY
DOI: 10.1002/ptr.6262
Keywords
acid-sensing ion channel; dorsal root ganglion neuron; dragon's blood resin; flavonoid; inflammatory thermal hyperalgesia model
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Funding
- National Science Foundation of Hubei [2014CFB455]
- National Natural Science Foundation of China [81403186]
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Acid-sensing ion channel (ASIC) serves important roles in the transmission of nociceptive information. To confirm the analgesic mechanism of dragon's blood resin, patch-clamp technique, in vivo animal experiments, and immunohistochemical staining were used to observe the effects of the three flavonoids (loureirin B, cochinchinemin A, and cochinchinemin B) isolated from dragon's blood resin on ASIC. Results showed that the three flavonoids exerted various inhibitory effects on ASIC currents in rat dorsal root ganglion (DRG) neurons. The combination of the three flavonoids with total concentration of 6.5 mu M could decrease (53.8 +/- 4.3%) of the peak amplitude and (45.8 +/- 4.5%) of the sustained portion of ASIC currents. The combination of the three flavonoids was fully efficacious on complete Freud's adjuvant (CFA)-induced inflammatory thermal hyperalgesia at a dose of 6.5 mM similar with amiloride at 10 mM. The analgesic effects of the combination could be weakened by an ASIC activator 2-guanidine-4-methylquinazoline. CFA-induced hyperalgesia was accompanied by c-Fos up-regulation in DRG neurons, and the combination rescued thermal hyperalgesia through down-regulation of c-Fos and ASIC3 expression in CFA-induced inflammation. These collective results suggested that the flavonoids isolated from dragon's blood resin could be considered as the chemical compounds that exert analgesic effects on inflammatory thermal pain due to action on ASIC.
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