title: Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2, and autophagy pathways.
abstract: Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has been shown to be neuroprotective in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of sulforaphane in an in vivo Parkinson's disease (PD) model, based on rotenone-mediated neurotoxicity. Our results showed that sulforaphane inhibited rotenone-induced locomotor activity deficiency and dopaminergic neuronal loss. Additionally, sulforaphane treatment inhibited the rotenone-induced reactive oxygen species production, malondialdehyde (MDA) accumulation, and resulted in an increased level of total glutathione and reduced glutathione (GSH): oxidized glutathione (GSSG) in the brain. Western blot analysis illustrated that sulforaphane increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1), the latter two of which are anti-oxidative enzymes. Moreover, sulforaphane treatment significantly attenuated rotenone-inhibited mTOR-mediated p70S6K and 4E-BP1 signalling pathway, as well as neuronal apoptosis. In addition, sulforaphane rescued rotenone-inhibited autophagy, as detected by LC3-II. Collectively, these findings demonstrated that sulforaphane exert neuroprotective effect involving Nrf2-dependent reductions in oxidative stress, mTOR-dependent inhibition of neuronal apoptosis, and the restoration of normal autophagy. Sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing PD.
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Nanjing Research Institute for Comprehensive Utilization of Wild Plants, Nanjing 210042, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
authors.forename: Xindong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Cai
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Wuguang
authors.initials: W
authors.lastname: Lu
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Huaijiang
authors.initials: H
authors.lastname: Yan
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ye
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Shen
authors.affiliation: Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.|Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D010300:Parkinson Disease / Q000209:etiology; D012402:Rotenone / Q000633:toxicity*; D013454:Sulfoxides; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D013454:Sulfoxides; D012402:Rotenone; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C016766:sulforaphane; D005978:Glutathione