Chen Dandan, Ren Qianqian, Lü Menglin, Zhang Baowen, Liu Xingran, Zhang Meng, Wang Yang, Kou Xianjuan
School of Sports Medicine, Wuhan Sports University, Wuhan 430079, China.
School of Physical Education, Guangxi University of Science and Technology, Liuzhou 545000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Aug 20;45(8):1571-1580. doi: 10.12122/j.issn.1673-4254.2025.08.01.
To investigate the effects of formulated granules of (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms.
Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment.
Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum.
TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
研究天麻颗粒（TGY）对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的亚急性帕金森病（PD）小鼠模型运动功能障碍的影响，并探讨其可能的分子机制。
将90只C57BL/6小鼠随机均分为6组，包括对照组、PD模型组、NEC-1（6.5mg/kg）治疗组、两个分别为5g/kg和2.5g/kg的TGY治疗组以及美多芭（76mg/kg）治疗（阳性对照）组。通过连续5天腹腔注射MPTP（30mg/kg）建立PD小鼠模型，并进行相应治疗15天。随机选取小鼠进行运动功能测试。采用蛋白质免疫印迹法检测小鼠纹状体中酪氨酸羟化酶（TH）、α-突触核蛋白（α-syn）、受体相互作用蛋白激酶1（RIPK1）、受体相互作用蛋白激酶3（RIPK3）和混合谱系激酶结构域样蛋白（MLKL）的表达变化。进行网络药理学分析和分子对接研究，以探索TGY介导的坏死性凋亡途径调控对PD治疗的作用。
与对照组相比，PD模型小鼠表现出明显的运动功能障碍，纹状体中α-syn蛋白表达显著增加，TH蛋白表达降低。NEC-1治疗明显改善了运动功能障碍，抑制了坏死性凋亡途径，并减轻了PD小鼠中TH和α-syn蛋白的变化。网络药理学和分子对接分析表明，TGY对PD的治疗作用与坏死性凋亡途径中的关键蛋白RIPK1的调节有关。在PD小鼠模型中，两个剂量的TGY治疗均显著改善了小鼠的运动功能障碍。增加了TH表达，并降低了纹状体中α-syn和坏死性凋亡相关蛋白的表达。
TGY可有效抑制坏死性凋亡途径，增加纹状体中TH表达，降低α-syn表达，从而改善PD小鼠的运动功能障碍。
