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 HO-induced apoptosis. The non-toxic level of SSD significantly mitigated the HO-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 HO-induced apoptosis by damaging the intracellular antioxidation system. SSD significantly slowed the HO-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 HO-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 HO-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 HO-induced PC12 cell apoptosis by removing ROS and blocking MAPK-dependent oxidative damage.

Fucoxanthin prevents H2O2-induced neuronal apoptosis via concurrently activating the PI3-K/Akt cascade and inhibiting the ERK pathway

“…[4,5] Therefore, we assessed whether the alteration of these pathways was also involved in our model. Figure 5 shows that H 2 O 2 decreased pSer473-Akt and pSer9-GSK3β levels in SH-SY5Y cells.…”

“…Inhibition of PI3-K/Akt cascade consequently activates glycogen synthase kinase 3β (GSK3β), a molecule involved in H 2 O 2 -induced neuronal apoptosis. [4,5] In addition, extracellular signal-regulated kinase (ERK), a key intermediate of the MAPK pathway, has been regarded as a main pro-apoptotic molecule involved in H 2 O 2 -induced neurotoxicity. [5,6]…”

Localization of malonyl and acetyl on substituted saikosaponins according to the full‐scan mass spectra and the fragmentation of sodium‐adduct ions in the positive mode

“…Saikosaponins exert significant pharmacological activities, including antitumor, chemosensitizing, radiosensitizing, anti‐inflammatory, hepatoprotective, nephroprotective, anti‐Alzheimer, neuroprotective, immune‐modulatory, anti‐virus, and so on. Saikosaponins are considered to be the major bioactive ingredients and the key markers for quality control of Radix Bupleuri , which is a famous traditional Chinese medicine (TCM) that has been used for more than 1000 years.…”

A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins

“…SSd also protected cisplatin-induced nephrotoxicity by repressing ROS accumulation and ROS-induced MAPK/NF-κB pathways (Ma et al, 2015). In addition, SSd exhibited neuroprotective effects on H 2 O 2 -induced oxidative damage in PC-12 cells and MPP + -induced oxidative stress and cytotoxicity in SHY5Y cells through inhibition of MAPK signaling and SIRT3 induction, respectively (Lin et al, 2016b;Yang et al, 2016;Yuan et al, 2014). Furthermore, SSd alleviated oxidative stress and following cell apoptosis and thus protected against ventilator-induced lung injury .…”

“…Oxidative stress plays a critical role in neuronal injury and is closely related with various neurodegenerative diseases (Higgins et al, 2010). SSd has also been found to significantly mitigate the H 2 O 2 -induced apoptosis by reducing the activation of caspase-3 and the cleavage of poly ADP-ribose polymerase (PARP), releasing of malonic dialdehyde (MDA) and lactate dehydrogenase, and by increasing the activity of superoxide dismutase (SOD) via MAPK signaling pathways (Lin et al, 2016b). In addition, SSd acts as GR agonist, regulates mitochondrial function and inhibits the translocation of GR to the mitochondria in cortisone-challenged PC-12 cells, accompanied with upregulation of anti-apoptotic signaling (Li et al, 2014b).…”