Abstract：
BACKGROUND: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed.
OBJECTIVE: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms.
METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized.
RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 μM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells.
CONCLUSIONS: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.
OBJECTIVE: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms.
METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized.
RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 μM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells.
CONCLUSIONS: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.
摘要：
背景：五味子，木兰科植物五味子的干燥成熟果实（Turcz。)Baill,是传统镇痛处方中常用的。研究表明，五味子提取物（SC）具有镇痛活性。然而,镇痛活性成分和确切机制尚未揭示。
目的：本研究旨在研究五味子的抗伤害性成分，评估其镇痛效果，并探索潜在的分子机制。
方法：研究了一系列公认的SC化合物对甘氨酸受体的影响。在三种疼痛模型中评估所鉴定的化合物的镇痛效果。使用膜片钳技术对重组细胞中表达的各种靶标进行了机理研究。这些目标包括甘氨酸受体，Nav1.7钠通道，Cav2.2钙通道等。同时,还利用了原代培养的脊髓背角（SDH）神经元和背根神经节（DRG）神经元。
结果：五味子乙素（SchB）是脊髓背角神经元中甘氨酸受体的正变构调节剂。SchB对脊髓背角神经元甘氨酸受体的EC50为2.94±0.28μM。在三个疼痛模型中，SchB的镇痛效果与相同剂量的吲哚美辛相当。此外,SchB挽救了PGE2诱导的对α3GlyR活性的抑制并减轻了持续性疼痛。值得注意的是,SchB还可以有效降低DRG神经元中动作电位的频率并抑制钠和钙通道。与DRG神经元的数据一致，还发现SchB显著阻断重组细胞中的Nav1.7钠通道和Cav2.2通道。
结论：我们的结果表明，五味子B,五味子的主要木脂素成分，可以通过作用于多个离子通道来发挥其镇痛作用，包括甘氨酸受体,Nav1.7通道，和Cav2.2频道。
目的：本研究旨在研究五味子的抗伤害性成分，评估其镇痛效果，并探索潜在的分子机制。
方法：研究了一系列公认的SC化合物对甘氨酸受体的影响。在三种疼痛模型中评估所鉴定的化合物的镇痛效果。使用膜片钳技术对重组细胞中表达的各种靶标进行了机理研究。这些目标包括甘氨酸受体，Nav1.7钠通道，Cav2.2钙通道等。同时,还利用了原代培养的脊髓背角（SDH）神经元和背根神经节（DRG）神经元。
结果：五味子乙素（SchB）是脊髓背角神经元中甘氨酸受体的正变构调节剂。SchB对脊髓背角神经元甘氨酸受体的EC50为2.94±0.28μM。在三个疼痛模型中，SchB的镇痛效果与相同剂量的吲哚美辛相当。此外,SchB挽救了PGE2诱导的对α3GlyR活性的抑制并减轻了持续性疼痛。值得注意的是,SchB还可以有效降低DRG神经元中动作电位的频率并抑制钠和钙通道。与DRG神经元的数据一致，还发现SchB显著阻断重组细胞中的Nav1.7钠通道和Cav2.2通道。
结论：我们的结果表明，五味子B,五味子的主要木脂素成分，可以通过作用于多个离子通道来发挥其镇痛作用，包括甘氨酸受体,Nav1.7通道，和Cav2.2频道。
