Department of Oriental Medicine, Institute of Bioscience and Integrative Medicine, Daejeon University, Daejeon, 34520, Republic of Korea.
J Ethnopharmacol. 2020 Oct 5;260:113063. doi: 10.1016/j.jep.2020.113063. Epub 2020 Jun 4.
Herbal formulation Buyang Huanwu Decoction (BYHWD) has been used to treat cardiovascular disorders including cerebral ischemia. Recent studies showed its effects on promoting axonal regeneration after nerve injury. However, compositional reformulation supplemented with herbal components that regulates inflammation may increase its efficacy for nerve repair.
We prepared a new herbal decoction by adding selected herbal components to BYHWD (augmented BYHWD; ABHD) and investigated the effect of ABHD on the production of inflammatory cytokines and axonal regeneration using an animal model of nerve transection and coaptation (NTC).
A rat model of NTC was performed on the sciatic nerve. The sciatic nerve and dorsal root ganglion (DRG) were isolated and used for immunofluorescence staining and western blot analysis. DRG tissue was also used to prepare primary neuron culture and the length of neurites was analyzed. Sensorimotor nerve activities were assessed by rotarod and von Frey tests.
Three herbal components that facilitated neurite outgrowth were chosen to formulate ABHD. ABHD administration into the sciatic nerve 1 week or 3 months after NTC facilitated axonal regeneration. Cell division cycle 2 (Cdc2) and brain-derived neurotrophic factor (BDNF) proteins were induced from the reconnected distal portion of the sciatic nerve and the levels were further elevated by in vivo administration of ABHD. Phospho-Erk1/2 level was increased by ABHD treatment as well, implying its role in mediating retrograde transport of BDNF signals into the neuronal cell body. Production of inflammatory cytokines IL-1β and TNF-α was induced in the reconnected nerve but attenuated by ABHD treatment. Behavioral tests revealed that ABHD treatment improved functional recovery of sensorimotor activities.
A newly formulated ABHD is effective at regulating the production of inflammatory cytokines and promoting axonal regeneration after nerve transection and may be considered to develop therapeutic strategies for peripheral nerve injury disorders.
草药配方补阳还五汤（BYHWD）已被用于治疗包括脑缺血在内的心血管疾病。最近的研究表明，它在促进神经损伤后的轴突再生方面具有作用。然而，通过补充调节炎症的草药成分进行配方改革可能会提高其神经修复的疗效。
我们通过向 BYHWD 中添加精选的草药成分来制备一种新的草药配方（增强型 BYHWD；ABHD），并通过神经横断和吻合（NTC）动物模型研究 ABHD 对炎症细胞因子产生和轴突再生的影响。
在坐骨神经上进行 NTC 大鼠模型。分离坐骨神经和背根神经节（DRG），进行免疫荧光染色和 Western blot 分析。还使用 DRG 组织制备原代神经元培养物，并分析神经突的长度。通过旋转棒和 von Frey 测试评估感觉运动神经活动。
选择了三种有利于神经突生长的草药成分来配方 ABHD。NTC 后 1 周或 3 个月将 ABHD 注入坐骨神经，可促进轴突再生。细胞分裂周期 2（Cdc2）和脑源性神经营养因子（BDNF）蛋白从重新连接的坐骨神经远端部分诱导，并且通过体内给予 ABHD 进一步升高。ABHD 处理也增加了磷酸化-Erk1/2 水平，暗示其在介导 BDNF 信号逆行运输到神经元细胞体中的作用。在重新连接的神经中诱导产生了炎症细胞因子 IL-1β和 TNF-α，但 ABHD 处理可减轻其产生。行为测试表明，ABHD 治疗可改善感觉运动活动的功能恢复。
新配方的 ABHD 可有效调节神经横断后炎症细胞因子的产生和促进轴突再生，可考虑将其用于治疗周围神经损伤疾病的治疗策略。
