title: Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra.
abstract: Parkinson's disease (PD) is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of aggregated α-synuclein in specific central nervous system (CNS) regions. Disease development is attributed to α-synuclein abnormalities, particularly aggregation and phosphorylation. The ginsenoside Rg1, an active component of ginseng, possesses neuroprotective and anti-inflammatory effects. The purpose of the present study was to evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms. Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the SNpc. Rg1 also alleviated the unusual MPTP-induced increase in oligomeric, phosphorylated and disease-related α-synuclein in the SNpc. In conclusion, Rg1 protects dopaminergic neurons, most likely by reducing aberrant α-synuclein-mediated neuroinflammation, and holds promise for PD therapeutics.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Heng
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Qiu-Shuang
authors.initials: QS
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: yuanyuhe@imm.ac.cn.
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. Electronic address: chennh@imm.ac.cn.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology*; D011339:Probenecid / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C035054:ginsenoside Rg1; D011339:Probenecid
keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Ginsenoside Rg1; Neuroinflammation; Parkinson’; s disease; α-Synuclein