title: Neolignans from Aristolochia fordiana Prevent Oxidative Stress-Induced Neuronal Death through Maintaining the Nrf2/HO-1 Pathway in HT22 Cells.
abstract: Bioassay-guided fractionation of the ethanolic extract of the stems of Aristolochia fordiana led to the isolation of six new dihydrobenzofuran neolignans (1-3 and 7-9), three new 2-aryldihydrobenzofurans (4-6), a new 8-O-4' neolignan (10), and 14 known analogues (11-24). The structures of compounds 1-10 were established by spectroscopic methods, and their absolute configurations were determined by analyses of the specific rotation and electronic circular dichroism data. The neuroprotective effects of compounds 1-24 against glutamate-induced cell death were tested in hippocampal neuronal cell line HT22. Compounds 17 and 20-24 exhibited moderate neuroprotective activity by increasing the endogenous antioxidant defense system. In addition, the neolignans activated the Nrf2 (nuclear factor E2-related factor 2) pathway, resulting in the increase of the expression of endogenous antioxidant protein HO-1 (heme oxygenase-1). The active compounds also preserved the levels of antiapoptotic protein Bcl-2 (B cell lymphoma/leukemia-2), which was decreased by glutamate. Collectively, these results suggested that the active neolignans protect neurons against glutamate-induced cell death through maintaining the Nrf2/HO-1 signaling pathway as well as preserving the Bcl-2 protein and might be promising novel beneficial agents for oxidative stress-associated diseases.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Zi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Longquanyi District Hospital of Traditional Chinese Medicine , Chengdu 610100, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Tan
authors.affiliation: The 2nd Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine , Guangzhou 510120, People's Republic of China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Jing-Mei
authors.initials: JM
authors.lastname: Bao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Zhong-Bin
authors.initials: ZB
authors.lastname: Cheng
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Zhang-Hua
authors.initials: ZH
authors.lastname: Sun
authors.affiliation: The 2nd Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine , Guangzhou 510120, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yin
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D030022:Aristolochia / Q000737:chemistry*; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D018384:Oxidative Stress / Q000187:drug effects*; D018547:Plant Stems / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D017705:Lignans; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1