Antiepileptic Effects of Cicadae Periostracum on Mice and Its Antiapoptotic Effects in H₂O₂‐Stimulated PC12 Cells via Regulation of PI3K/Akt/Nrf2 Signaling Pathways

Abstract

Cicadae Periostracum (CPM), a commonly used animal traditional Chinese medicine (TCM), possesses antifebrile, spasmolytic, antiasthmatic, and antiphlogistic effects. In our present paper, we aimed to systemically investigate the antiepileptic effects of CPM in epileptic mice and explore the related molecular mechanism. Pentylenetetrazole- (PTZ) and strychnine-induced convulsion mice were established, and the results showed CPM could prolong the latency of convulsion and death and improve the neuronal damage in the hippocampus of PTZ-induced mice. Furthermore, the H2O2-treated PC12 cells were prepared to explore the possible mechanisms for the antiepileptic effects of CPM. CCK-8 results showed that CPM significantly improved the cell viability of H2O2-treated PC12 cells. Results of the acridine orange- (AO-) ethidium bromide (EB) staining, cell mitochondrial membrane potential (MOMP) analysis, and flow cytometry analysis showed that CPM significantly suppressed the H2O2-induced apoptosis in PC12 cells. In addition, CPM also downregulated the proapoptosis proteins, including Bax, cleaved- (C-) caspase-3, and C-caspase-9, and upregulated Bcl-2. Furthermore, CPM reduced the reactive oxygen species (ROS) levels via increasing antioxidative enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Importantly, CPM could increase the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in H2O2-induced PC12 cells and can promote the nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) and increase the expression of heme oxygenase-1 (HO-1) in the cytoplasm. In conclusion, our present study suggested CPM possessed antiepileptic effects through antiapoptosis of neuron cells via regulation of the PI3K/Akt/Nrf2 signaling pathway.

Alpiniae oxyphyllae fructus possesses neuroprotective effects on H2O2 stimulated PC12 cells via regulation of the PI3K/Akt signaling Pathway

“…Subsequently, Cyt-C in the cytoplasm activates caspase-9, which in turn activates Caspase-3. As the ultimate executor of apoptosis, caspase-3 activation triggers the occurrence of apoptosis ( Zhang et al, 2021 ).…”

“…In addition, H 2 O 2 is a small molecule compound with high cell membrane permeability. At the same time, as an important member of the ROS family, H 2 O 2 can also generate hydroxyl radicals, which in turn cause oxidative stress and even cell death ( Zhang et al, 2021 ). Therefore, PC12 cells stimulated by H 2 O 2 are often used in drug screening models for various neurodegenerative diseases, and this model was also selected as a cell model to verify the anti-AD effect of AOF in this experiment ( Bie et al, 2021 ; Vahdati et al, 2022 ).…”

“…As research on AOF continues, there are more chemical components identified from AOF, which contains essential oils, sesquiterpenes (e.g., Nootkatone), flavones (e.g., Tectochrysin, Izalpinin, Chrysin, and Kaempferide), diarylheptanoids (e.g., TYakuchinone A and B and Oxyphyllacinol), glycosides, steroids and so on ( Chen et al, 2014 ; Zhang et al, 2015 ). In addition, more effects of AOF have been reported, such as, anti-cancer, anti-inflammatory, analgesic, anti-allergic, insecticidal, anti-parasitic, anti-microbial and anti-oxidant properties ( Yu et al, 2003 ; Zhang et al, 2011 ; Chang et al, 2017 ; Qi et al, 2019 ). Similarly, AOF was surprisingly found to have anti-AD effects, such as Shenqi Yizhi Decoction and Yizhi Decoction ( Liu and Hong, 2017 ; Wang et al, 2022 ).…”

Anti-depression effectiveness of essential oil from the fruits of Zanthoxylum bungeanum maxim. on chronic unpredictable mild stress-induced depression behavior in mice

“…JC-1 was commonly considered a perfect probe for assessing ΔΨm. In addition, apoptosis rate was measure by flow cytometry analysis ( Zhang et al, 2021a ). Our results revealed that treatment with HEO remarkably decrease apoptosis in CORT-injured PC12 cells.…”

An Integrated Approach Based on Network Analysis Combined With Experimental Verification Reveals PI3K/Akt/Nrf2 Signaling Is an Important Way for the Anti-Myocardial Ischemia Activity of Yi-Qi-Tong-Luo Capsule

“…Therefore, it is necessary to identify more safe and effective drugs for MI. With a long history of clinic use, Traditional Chinese medicine (TCM) has great advantages to treat cardiovascular diseases ( Duan et al, 2021 ; Zhang et al, 2021a ), which can be seen as a resource library for alternative drugs of MI ( Wu et al, 2020 ).…”