Abstract
Cynandione A, an acetophenone isolated from Cynanchum Wilfordii Radix, exhibits antineuropathic pain effect. This study further explored the target molecule and signaling mechanisms underlying cynandione-A-induced antineuropathic pain. Intrathecal injection of cynandione A significantly attenuated mechanical allodynia in neuropathic rats and substantially increased spinal expression of IL-10 and β-endorphin but not dynorphin A. Cynandione A treatment also enhanced expression of IL-10 and β-endorphin but not α7 nicotinic acetylcholine receptors (nAChRs) in cultured microglia. The IL-10 antibody attenuated cynandione-A-induced spinal or microglial gene expression of β-endorphin and mechanical allodynia, whereas the β-endorphin antiserum blocked cynandione-A-induced mechanical antiallodynia but not spinal or microglial IL-10 gene expression. The α7 nAChR antagonist methyllycaconitine significantly reduced cynandione-A-induced mechanical antiallodynia and spinal or microglial expression of IL-10 and β-endorphin. Furthermore, cynandione A stimulated microglial phosphorylation of PKA, p38, and CREB in an α7-nAChR-dependent manner, and treatment with their inhibitors attenuated cynandione-A-induced mechanical antiallodynia and spinal or microglial expression of IL-10 and β-endorphin. In addition, cynandione A stimulated spinal phosphorylation of the transcription factor STAT3, which was inhibited by methyllycaconitine, the PKA activation inhibitor or IL-10 antibody. The STAT3 inhibitor NSC74859 also abolished cynandione-A-induced mechanical antiallodynia and spinal expression of β-endorphin. These findings suggest that cynandione A suppresses neuropathic pain through α7-nAChR-dependent IL-10/β-endorphin signaling pathway in spinal microglia.
Highlights
Cynanchum Wilfordii has long been used in the East Asian countries especially in China, Korea, and Japan as a traditional herb medicine for the treatment of insomnia, anxiety, anemia, senescence, and various geriatric diseases (Gong et al, 1988; Hwang et al, 1999; Koo et al, 2015)
Our results demonstrated that cynandione A produces mechanical antiallodynia in neuropathic pain through spinal microglial IL-10 expression via the cAMP/PKA/p38/CREB signaling and subsequent β-endorphin expression via the IL-10/STAT3 signaling in an α7-nicotinic acetylcholine receptors (nAChRs)-dependent manner
We have previously demonstrated that intrathecal injection of cynandione A dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in neuropathic pain, with Emax values of 57 and 59% maximum possible effect and ED50 values of 14.9 and 6.5 μg, respectively (Huang et al, 2017)
Summary
Cynanchum Wilfordii has long been used in the East Asian countries especially in China, Korea, and Japan as a traditional herb medicine for the treatment of insomnia, anxiety, anemia, senescence, and various geriatric diseases (Gong et al, 1988; Hwang et al, 1999; Koo et al, 2015). It has been demonstrated to reduce LPS-induced expression of TNF-α, IL-6, IL-1β, nitric oxide and Cynandione A Inhibits Mechanical Allodynia prostaglandin E2 in BV-2 microglia, RAW264.7 macrophages and primary microglia, as well as in septic mice and neuropathic rats (Yang et al, 2014; Kim et al, 2015; Huang et al, 2017). It attenuated glutamate-induced cytotoxicity and mitigated ischemic injuries in rats with cerebral ischemia (Yue et al, 2012) and protected cultured cortical neurons from toxicity induced by hydrogen peroxide, L-glutamate, and kainate (Lee et al, 2000). Little is known about the upstream signaling and target molecule mechanisms of cynandione A, its antinociception was blocked by the α7 nicotinic acetylcholine receptor (α7 nAChR) antagonist in our preliminary experiment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
