Hydroxy-α-sanshool Possesses Protective Potentials on H₂O₂-Stimulated PC12 Cells by Suppression of Oxidative Stress-Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway

Abstract

<jats:p><jats:italic>Zanthoxylum bungeanum</jats:italic> pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy-<jats:italic>α</jats:italic>-sanshool (HAS) is the most important active ingredient of <jats:italic>Z. bungeanum</jats:italic> pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.</jats:p>

The Cyr61 Is a Potential Target for Rotundifuran, a Natural Labdane‐Type Diterpene from Vitex trifolia L., to Trigger Apoptosis of Cervical Cancer Cells

“…The mitochondrial-dependent apoptosis is one of the most important pathways for cell death, and proteins in caspase and Bcl-2 families are the dominant regulators in this apoptotic pathway [ 19 , 20 ]. The results of our present study ( Figure 4(a) ) revealed that RTF treatment (8 and 16 μ M) could statistically upregulate the cleaved caspase family proteins (cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9) and proapoptotic Bcl-2 family proteins (Bax and Bim), while statistically downregulating the antiapoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL) compared to the control cells.…”

“…Furthermore, the unlabeled quantitative proteomics analysis was carried out to explore the deep possible mechanisms of antitumor effects of RTF, and the related KEGG analysis based on differential proteins revealed that PI3K/Akt and MAPK signaling pathways might be related to the antitumor effects of RTF (data not shown). Previous scientific reports demonstrated that PI3K/Akt and MAPK signaling pathways are also closely involved in the ROS-induced mitochondrial-dependent apoptosis [ 19 , 26 , 27 ]. Consequently, we examined the related proteins in the two signal pathways and found that RTF treatment could downregulate the phosphorylation of PI3K, Akt, and ERK, while upregulating the phosphorylation of JNK in HeLa cells.…”

Inducing Apoptosis and Suppressing Inflammatory Reactions in Synovial Fibroblasts are Two Important Ways for Guizhi-Shaoyao-Zhimu Decoction Against Rheumatoid Arthritis

“…Mitochondrial function is important for the survival of cells, and the decreased mitochondrial membrane potential (MMOP, Δ Ψ ) could induce the apoptosis of cells. 43 , 44 In addition, the flow cytometry analysis with fluorescent double staining is another important way for determining the apoptosis in cells. 45 The results of this study showed that GSZD could reduce the MOMP in MH7A cells, and increase the level of apoptosis.…”

Six-ingredient-Xiao-qing-long decoction inhibited TGF-β1-induced proliferation and migration of human airway smooth muscle cells by regulating FKBP51/AKT signaling

“…AKT also known as protein kinase B, is activated by various stimuli, growth factors and hormones (Risso et al 2015;Song et al 2019). It has been reported that Akt plays a crucial role in cell survival and development (Li et al 2020), and the activation of AKT is involved in regulating the proliferation and migration of hASMC (Deng et al 2017;Lin et al 2019). A previous study demonstrated that AKT activation was significantly increased in hASMC induced by TGF-β1, while inhibition of the AKT signaling pathway significantly decreases hASMC migration (Lv et al 2019).…”