Neuroprotective effects of kukoamine A on 6-OHDA-induced Parkinson’s model through apoptosis and iron accumulation inhibition

作     者：Xin Li Xiao-wen Jiang Hai-xiao Chu Qing-chun Zhao Huai-wei Ding Chao-hong Cai Xin Li;Xiao-wen Jiang;Hai-xiao Chu;Qing-chun Zhao;Huai-wei Ding;Chao-hong Cai

作者机构：Department of PharmacyGeneral Hospital of Northern Theater CommandShenyang 110840China Key Laboratory of Structure-Based Drug Design and DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Department of Traditional Chinese MedicineShenyang Pharmaceutical UniversityShenyang 110016China 

出 版 物：《Chinese Herbal Medicines》 (中草药（英文版）)

年 卷 期：2021年第13卷第1期

页      面：105-115页

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1005[医学-中医学] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：supported by the Natural Science Foundation of Liaoning Province China.(Project number:20170540945)。 

主　　题：6-OHDA iron chelation iron homeostasis kukoamine A neuroprotection Parkinson’s disease 

摘      要：Objective: Parkinson’s disease(PD) is characterized by the loss of dopaminergic neurons in substantia nigra(SN). Our previous study demonstrated kukoamine A(KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP+-induced PD models in vivo and in vitro. It is necessary to evaluate the efficacy of the anti-PD effects under various models.Methods: In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex. Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD.Results: Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential(MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of a-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxininduced PD due to the apoptosis inhibition and iron homeostasis maintaining.Conclusion: KuA treatment might represent a neuroprotective treatment for PD.