title: Neuroprotective Effects of Tanshinone I Against 6-OHDA-Induced Oxidative Stress in Cellular and Mouse Model of Parkinson's Disease Through Upregulating Nrf2.
abstract: In this study, we investigated whether tanshinone I (T-I) has therapeutic effects in cellular and animal model of Parkinson's disease (PD), and explore its possible mechanism. For this purpose, human neuroblastoma SH-SY5Y cells were cultured and exposed to 100 μM 6-hydroxydopamine (6-OHDA) in the absence or presence of T-I (1, 2.5 and 5 μM). The results revealed that 6-OHDA-induced cell death was reduced by T-I pretreatment as measured by MTT assay, lactate dehydrogenase release and flow cytomety analysis of cell apoptosis. The increase in the reactive oxygen species caused by 6-OHDA treatment was also attenuated by T-I in SH-SY5Y cells. T-I pretreatment was also shown to result in an increase in nuclear factor erythroid-2-related factor 2 (Nrf2) protein levels and its transcriptional activity as well as the upregulation of Nrf2-dependent genes encoding the antioxidant enzymes heme oxygenase-1, glutathione cysteine ligase regulatory subunit and glutathione cysteine ligase modulatory subunit in SH-SY5Y cells. Moreover, in the in vivo experiment, T-I treatment significantly attenuated 6-OHDA-induced striatal oxidative stress and ameliorated dopaminergic neurotoxicity in 6-OHDA-lesioned mice, as evidenced by western blot analysis of tyrosine hydroxylase (TH) and TH immunostaining of dopaminergic neurons in the substantia nigra and the striatum. Taken together, the results suggest that T-I may be beneficial for the treatment of neurodegenerative diseases like PD.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.|Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
authors.forename: Manru
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
authors.forename: Lingtian
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong Province, China. louhaiyan@sdu.edu.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lou
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D061745:Antioxidant Response Elements; D016923:Cell Death; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D045784:Abietanes; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; C021751:tanshinone; D016627:Oxidopamine
keywords: 6-OHDA; Nrf2; Parkinson’s disease; Tanshinone I