Schisandrin B Induced ROS-Mediated Autophagy and Th1/Th2 Imbalance via Selenoproteins in Hepa1-6 Cells

Abstract

Schisandrin B (Sch B) is well-known for its antitumor effect; however, its underlying mechanism remains confusing. Our study aimed to investigate the role of selenoproteins in Sch B-induced autophagy and Th1/Th2 imbalance in Hepa1-6 cells. Hepa1-6 cells were chosen to explore the antitumor mechanism and were treated with 0, 25, 50, and 100 μM of Sch B for 24 h, respectively. We detected the inhibition rate of proliferation, transmission electron microscopy (TEM), monodansylcadaverine (MDC) staining, reactive oxygen species (ROS) level and oxidative stress-related indicators, autophagy-related genes, related Th1/Th2 cytokines, and selenoprotein mRNA expression. Moreover, the heat map, principal component analysis (PCA), and correlation analysis were used for further bioinformatics analysis. The results revealed that Sch B exhibited well-inhibited effects on Hepa1-6 cells. Subsequently, under Sch B treatment, typical autophagy characteristics were increasingly apparent, and the level of punctate MDC staining enhanced and regulated the autophagy-related genes. Overall, Sch B induced autophagy in Hepa1-6 cells. In addition, Sch B-promoted ROS accumulation eventually triggered autophagy initiation. Results of Th1 and Th2 cytokine mRNA expression indicated that Th1/Th2 immune imbalance was observed by Sch B treatment in Hepa1-6 cells. Intriguingly, Sch B downregulated the majority of selenoprotein expression. Also, the heat map results observed significant variation of autophagy-related genes, related Th1/Th2 cytokines, and selenoprotein expression in response to Sch B treatment. PCA outcome suggested the key role of Txnrd1, Txnrd3, Selp, GPX2, Dio3, and Selr with its potential interactions in ROS-mediated autophagy and Th1/Th2 imbalance of Hepa1-6 cells. In conclusion, Sch B induced ROS-mediated autophagy and Th1/Th2 imbalance in Hepa1-6 cells. More importantly, the majority of selenoproteins were intimately involved in the process of autophagy and Th1/Th2 imbalance, Txnrd3, Selp, GPX2, Dio3, and Selr had considerable impacts on the process.

miR‐210/NF‐κB axis: A new direction for regulating cadmium‐induced pig artery inflammatory injury

“…Necroptosis has also been shown to be a key driver of inflammation induced by RIPK3 (Zhang et al, 2019b). Meanwhile, Th1/Th2 imbalance caused by overproduction of ROS is also an important factor in cell death (Tan et al, 2022). Qin et al (2020) believed that oxidative stress caused by selenium deficiency could induce windpipe immune damage of chickens by changed the expressions of IFN‐γ, IL‐2, IL‐4, and IL‐6.…”

CeO2/Bovine Serum Albumin Nanoclusters with Robust Reactive Oxygen Species Scavenging and Improved Endothelial Dysfunction Abilities for the Treatment of Pulmonary Hypertension

“…The results revealed that the most significant enrichment of these 273 mRNAs was the Th1 and Th2 cell differentiation (Figure 7d). It has been reported that there is a potential interaction between ROS and Th1/ Th2 imbalance, 30 which may be the potential mechanism of the CeO 2 /BSA nanocluster treatment. GO analysis also showed that differential mRNAs were part of inflammationrelated pathways, including the immunoglobulin complex, immunoglobulin receptor binding, and immune response (Figure S9).…”

The Use of Schisandrin B to Combat Triple-Negative Breast Cancers by Inhibiting NLRP3-Induced Interleukin-1β Production

“…Schisandrin B (Sch B), a compound extracted from Schisandra chinensis, has previously been used to treat liver diseases [7][8][9]. Lately, investigations have claimed the beneficial effect of Sch B against different tumors such as cholangiocarcinoma [10], hepatoma [11], gastric cancer [12], glioma [13], prostate cancer [14], and multi-drug-resistant breast cancer [15]. Research has suggested that Sch B is able to restore the drug sensitivity of multi-drug-resistant MCF-7 cells [15].…”