Liu Quanfeng, Sang Heon Kim, Yung-Wei Sung, Sok Cheon Pak, Wonwoong Lee, Jongki Hong, Jaehwan Jang, Kyoung Sang Cho, Songhee Jeon, Byung-Soo Koo
Department of Oriental Medicine, Dongguk University, Gyeogju, 38066, Republic of Korea.
Department of Oriental Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Gyeonggi-do 10326, Republic of Korea.
J Tradit Chin Med. 2019 Dec;39(6):800-808.
To examine the role of KSOP1009 (a modified formulation of Suhexiang Wan essential oil) in an animal model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection.
Cell toxicity, apoptosis, and reactive oxygen species (ROS) levels were analyzed in the human neuroblastoma cell line SH-SY5Y. After that, changes in animal behavior and tyrosine hydroxylase (TH) protein levels in the substantia nigra (SN) of MPTP-injected mice were examined. Three different doses of KSOP1009 (30, 100, and 300 mg/kg, n = 8 for each group) were administered daily for 7 d before MPTP injection and 14 d after MPTP injection, totaling 21 d.
MPP+, the active metabolite of MPTP, decreased the viability of SH-SY5Y cells, whereas KSOP1009 alleviated MPP+-induced cytotoxicity. KSOP1009 (10 and 50 mg/mL) reduced MPP+-induced ROS generation compared with the control group. Treatment with 1 mM MPP+ increased the percentage of depolarized/live cells, whereas KSOP1009 intake at a dose of 10 mg/mL decreased the percentage of these cells. The mean latency to fall in the rotarod test was reduced in mice treated with MPTP compared with the control group. However, mice receiving three different doses of KSOP1009 performed better than MPTP-treated animals. MPTP-treated mice were more hesitant and took longer to traverse the balance beam than the control animals. In contrast, KSOP1009-treated mice performed significantly better than MPTP- treated mice. Furthermore, the KSOP1009-treated groups had a significantly higher number of TH-positive neurons in the lesioned SN and significantly higher expression of TH in the striatum than the MPTP-treated group. MPTP treatment strongly induced Jun-N-terminal kinase (JNK) activation, whereas KSOP1009 suppressed MPTP-induced JNK activation. In addition, KSOP1009 intake reversed the decrease in the phosphorylation levels of cAMP-response element-binding protein in the brain of MPTP-treated mice. KSOP1009 also restored the decrease in dopaminergic neurons and dopamine levels in the brain of MPTP-treated mice.
KSOP1009 protected mice against MPTP-induced toxicity by decreasing ROS formation and restoring mitochondrial function.
研究KSOP1009（苏合香丸精油的改良制剂）在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）注射诱导的帕金森病（PD）动物模型中的作用。
对人神经母细胞瘤细胞系SH-SY5Y进行细胞毒性、凋亡及活性氧（ROS）水平分析。之后，检测MPTP注射小鼠的动物行为变化及黑质（SN）中酪氨酸羟化酶（TH）蛋白水平。在MPTP注射前7天及注射后14天，每天给予三种不同剂量的KSOP1009（30、100和300 mg/kg，每组n = 8），共21天。
MPTP的活性代谢产物MPP +降低了SH-SY5Y细胞的活力，而KSOP1009减轻了MPP +诱导的细胞毒性。与对照组相比，KSOP1009（10和50 mg/mL）降低了MPP +诱导的ROS生成。用1 mM MPP +处理增加了去极化/活细胞的百分比，而以10 mg/mL剂量摄入KSOP1009降低了这些细胞的百分比。与对照组相比，MPTP处理的小鼠在转棒试验中的平均跌落潜伏期缩短。然而，接受三种不同剂量KSOP1009的小鼠表现优于MPTP处理的动物。与对照动物相比，MPTP处理的小鼠在走过平衡木时更犹豫，花费时间更长。相比之下，KSOP1009处理的小鼠表现明显优于MPTP处理的小鼠。此外，与MPTP处理组相比，KSOP1009处理组在受损SN中TH阳性神经元数量明显更多，纹状体中TH表达明显更高。MPTP处理强烈诱导Jun-N末端激酶（JNK）激活，而KSOP1009抑制MPTP诱导的JNK激活。此外，摄入KSOP1009逆转了MPTP处理小鼠脑中cAMP反应元件结合蛋白磷酸化水平的降低。KSOP1009还恢复了MPTP处理小鼠脑中多巴胺能神经元和多巴胺水平的降低。
KSOP1009通过减少ROS形成和恢复线粒体功能保护小鼠免受MPTP诱导的毒性。
