Zhao Qianru, Zhang Xu, Long Siru, Wang Shaobing, Yu Hui, Zhou Yongsheng, Li Yi, Xue Lu, Hu Yan, Yin Shijin
Department of Chemical Biology, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, People's Republic of China (Q.Z., X.Z., S.L., S.W., H.Y., Y.Z., Y.H., S.Y.) and Institute for Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central Minzu University, Wuhan, People's Republic of China (Y.L., L.X.).
Department of Chemical Biology, School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, People's Republic of China (Q.Z., X.Z., S.L., S.W., H.Y., Y.Z., Y.H., S.Y.) and Institute for Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central Minzu University, Wuhan, People's Republic of China (Y.L., L.X.)
Mol Pharmacol. 2023 Oct;104(4):133-143. doi: 10.1124/molpharm.122.000658. Epub 2023 Jul 7.
Licorice is a traditional Chinese medicine and recorded to have pain relief effects in national pharmacopoeia, but the mechanisms behind these effects have not been fully explored. Among the hundreds of compounds in licorice, licochalcone A (LCA) and licochalcone B (LCB) are two important components belonging to the chalcone family. In this study, we compared the analgesic effects of these two licochalcones and the molecular mechanisms. LCA and LCB were applied in cultured dorsal root ganglion (DRG) neurons, and the voltage-gated sodium (Na) currents and action potentials were recorded. The electrophysiological experiments showed that LCA can inhibit Na currents and dampen excitabilities of DRG neurons, whereas LCB did not show inhibition effect on Na currents. Because the Na1.7 channel can modulate Subthreshold membrane potential oscillations in DRG neuron, which can palliate neuropathic pain, HEK293T cells were transfected with Na1.7 channel and recorded with whole-cell patch clamp. LCA can also inhibit Na1.7 channels exogenously expressed in HEK293T cells. We further explored the analgesic effects of LCA and LCB on formalin-induced pain animal models. The animal behavior tests revealed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, and LCB can inhibit the pain responses during phase 2. The differences of the effects on Na currents between LCA and LCB provide us with the basis for developing Na channel inhibitors, and the novel findings of analgesic effects indicate that licochalcones can be developed into effective analgesic medicines. SIGNIFICANCE STATEMENT: This study found that licochalcone A (LCA) can inhibit voltage-gated sodium (Na) currents, dampen excitabilities of dorsal root ganglion neurons, and inhibit the Na1.7 channels exogenously expressed in HEK293T cells. Animal behavior tests showed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, whereas licochalcone B can inhibit the pain responses during phase 2. These findings indicate that licochalcones could be the leading compounds for developing Na channel inhibitors and effective analgesic medicines.
甘草是一种传统中药，《中国药典》记载其具有止痛作用，但其作用机制尚未完全阐明。甘草中数百种化合物中，光甘草定（LCA）和光甘草酮（LCB）是查尔酮家族的两个重要成分。本研究比较了这两种光甘草查尔酮的镇痛作用及其分子机制。将LCA和LCB作用于培养的背根神经节（DRG）神经元，记录电压门控钠（Na）电流和动作电位。电生理实验表明，LCA可抑制Na电流并降低DRG神经元的兴奋性，而LCB对Na电流无抑制作用。由于Na1.7通道可调节DRG神经元阈下膜电位振荡，从而缓解神经性疼痛，因此将Na1.7通道转染至HEK293T细胞中，并用全细胞膜片钳进行记录。LCA还可抑制在HEK293T细胞中过表达的Na1.7通道。我们进一步探究了LCA和LCB对福尔马林诱导的疼痛动物模型的镇痛作用。动物行为学实验表明，LCA可抑制福尔马林试验第1期和第2期的疼痛反应，而LCB可抑制第2期的疼痛反应。LCA和LCB对Na电流作用的差异为开发Na通道抑制剂提供了依据，而镇痛作用的新发现表明光甘草查尔酮可开发成有效的镇痛药。意义声明：本研究发现，光甘草定（LCA）可抑制电压门控钠（Na）电流，降低背根神经节神经元的兴奋性，并抑制在HEK293T细胞中过表达的Na1.7通道。动物行为学实验表明，LCA可抑制福尔马林试验第1期和第2期的疼痛反应，而光甘草酮可抑制第2期的疼痛反应。这些发现表明，光甘草查尔酮可能是开发Na通道抑制剂和有效镇痛药的先导化合物。
