title: Saikosaponin-D Reduces H2O2-Induced PC12 Cell Apoptosis by Removing ROS and Blocking MAPK-Dependent Oxidative Damage.
abstract: Neuronal oxidative stress (OS) injury has been proven to be associated with many neurodegenerative diseases, and thus, antioxidation treatment is an effective method for treating these diseases. Saikosaponin-D (SSD) is a sapogenin extracted from Bupleurum falcatum and has been shown to have many pharmacological activities. The main purpose of this study was to investigate whether and how SSD protects PC12 cells from H2O2-induced apoptosis. The non-toxic level of SSD significantly mitigated the H2O2-induced decrease in cell viability, reduced the apoptosis rate, improved the nuclear morphology, and reduced caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Additionally, exogenous H2O2-induced apoptosis by damaging the intracellular antioxidation system. SSD significantly slowed the H2O2-induced release of malonic dialdehyde (MDA) and lactate dehydrogenase and increased the activity of superoxide dismutase (SOD) and the total antioxidant capacity, thereby reducing apoptosis. More importantly, SSD effectively blocked H2O2-induced phosphorylation of extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38MAPK), and specific inhibitors of ERK, JNK, and p38-reduced OS injury and apoptosis, suggesting that SSD reduces OS injury and apoptosis via MAPK signalling pathways. Finally, we confirmed that SSD significantly reduced H2O2-induced reactive oxygen species (ROS) accumulation, and the ROS inhibitor blocked the apoptosis caused by MAPK activation and cellular oxidative damage. In short, our study confirmed that SSD reduces H2O2-induced PC12 cell apoptosis by removing ROS and blocking MAPK-dependent oxidative damage.
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China.
authors.forename: Songdi
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhi
authors.affiliation: Department of Neurology, The First Hospital of Xi'an, No. 30, Powder Lane, South Street, Xi'an, 710002, China. wangfangEDU@foxmail.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D029972:Bupleurum / Q000737:chemistry; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012503:Saponins; D009828:Oleanolic Acid; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C025759:saikosaponin D
keywords: Cell apoptosis; Oxidative stress; PC12 cell; Reactive oxygen species; Saikosaponin-D