Park Hyun Jin, Zhao Ting Ting, Kim Seung Hwan, Lee Chong Kil, Hwang Bang Yeon, Lee Kyung Eun, Lee Myung Koo
Department of Pharmacy, College of Pharmacy; Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
Neural Regen Res. 2020 Feb;15(2):361-368. doi: 10.4103/1673-5374.265557.
Gynostemma (G.) pentaphyllum (Cucurbitaceae) contains various bioactive gypenosides. Ethanol extract from G. pentaphyllum (GP-EX) has been shown to have ameliorative effects on the death of dopaminergic neurons in animal models of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 6-hydroxydopamine. PD patients exhibit multiple symptoms, so PD-related research should combine neurotoxin models with genetic models. In the present study, we investigated the ameliorative effects of GP-EX, including gypenosides, on the cell death of dopaminergic neurons in the midbrain of A53T α-synuclein transgenic mouse models of PD (A53T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53T mice for 20 weeks. α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53T mice, which was reduced following treatment with GP-EX. Treatment with GP-EX modulated the reduced phosphorylation of tyrosine hydroxylase, extracellular signal-regulated kinase (ERK1/2), Bcl-2-associated death promoter (Bad) at Ser112, and c-Jun N-terminal kinase (JNK1/2) due to α-synuclein overexpression. In the A53T group, GP-EX treatment prolonged the latency of the step-through passive avoidance test and shortened the transfer latency of the elevated plus maze test. Gypenosides treatment exhibited the effects and efficacy similar to those of GP-EX. Taken together, GP-EX, including gypenosides, has ameliorative effects on dopaminergic neuronal cell death due to the overexpression of α-synuclein by modulating ERK1/2, Bad at Ser112, and JNK1/2 signaling in the midbrain of A53T mouse model of PD. Further studies are needed to investigate GP-EX as a treatment for neurodegenerative synucleinopathies, including PD. This study was approved by the Animal Ethics Committee of Chungbuk National University (approval No. CBNUA-956-16-01) on September 21, 2016.
绞股蓝（葫芦科）含有多种具有生物活性的绞股蓝皂苷。绞股蓝乙醇提取物（GP-EX）已被证明对1-甲基-4-苯基-1,2,3,6-四氢吡啶和6-羟基多巴胺诱导的帕金森病（PD）动物模型中多巴胺能神经元的死亡具有改善作用。PD患者表现出多种症状，因此与PD相关的研究应将神经毒素模型与遗传模型相结合。在本研究中，我们研究了GP-EX（包括绞股蓝皂苷）对A53T α-突触核蛋白转基因PD小鼠模型（A53T）中脑多巴胺能神经元细胞死亡的改善作用。将GP-EX和每天50mg/kg的绞股蓝皂苷口服给予A53T小鼠，持续20周。A53T小鼠中脑α-突触核蛋白免疫阳性细胞和α-突触核蛋白磷酸化增加，经GP-EX治疗后减少。GP-EX治疗调节了由于α-突触核蛋白过表达导致的酪氨酸羟化酶、细胞外信号调节激酶（ERK1/2）、丝氨酸112位点的Bcl-2相关死亡促进因子（Bad）和c-Jun氨基末端激酶（JNK1/2）磷酸化的降低。在A53T组中，GP-EX治疗延长了穿梭箱被动回避试验的潜伏期，并缩短了高架十字迷宫试验的转移潜伏期。绞股蓝皂苷治疗表现出与GP-EX相似的效果和功效。综上所述，GP-EX（包括绞股蓝皂苷）通过调节A53T PD小鼠模型中脑的ERK1/2、丝氨酸112位点的Bad和JNK1/信号，对α-突触核蛋白过表达引起的多巴胺能神经元细胞死亡具有改善作用。需要进一步研究将GP-EX作为包括PD在内的神经退行性突触核蛋白病的治疗方法。本研究于2016年9月21日获得忠北国立大学动物伦理委员会批准（批准号：CBNUA-956-16-01）。
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