Ethanol extract from Gynostemma pentaphyllum ameliorates dopaminergic neuronal cell death in transgenic mice expressing mutant A53T human alpha-synuclein

作     者：Hyun Jin Park Ting Ting Zhao Seung Hwan Kim Chong Kil Lee Bang Yeon Hwang Kyung Eun Lee Myung Koo Lee Hyun Jin Park;Ting Ting Zhao;Seung Hwan Kim;Chong Kil Lee;Bang Yeon Hwang;Kyung Eun Lee;Myung Koo Lee

作者机构：Department of PharmacyCollege of PharmacyChungbuk National UniversityCheongjuRepublic of Korea 2Research Center for Bioresource and HealthCollege of PharmacyChungbuk National UniversityCheongjuRepublic of Korea Department of Social Physical EducationSongwon UniversityGwangjuRepublic of Korea 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第2期

页      面：361-368页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100104[医学-病理学与病理生理学] 10[医学] 

基　　金：supported by the National Research Foundation of Korea grant No.2016R1D1A3B03930722(to MKL) Republic of Korea 

主　　题：A53T α-synuclein genetic mice ERK1/2 gynostemma pentaphyllum gypenosides Parkinson’s disease retention transfer latency time 

摘      要：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 A53 T α-synuclein transgenic mouse models of PD(A53 T). Both GP-EX and gypenosides at 50 mg/kg per day were orally administered to the A53 T mice for 20 weeks.α-Synuclein-immunopositive cells and α-synuclein phosphorylation were increased in the midbrain of A53 T 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 A53 T 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 A53 T 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.