Ginsenosides induce extensive changes in gene expression and inhibit oxidative stress-induced apoptosis in human lens epithelial cells

Zhewen Wang,Shiping Zhou,Jiannan Chai,Xiaoqing Hu

doi:10.1186/s12906-020-2826-8

Zhewen Wang, Shiping Zhou + Show 2 more

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https://doi.org/10.1186/s12906-020-2826-8

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Abstract

BackgroundThe effect of ginsenosides on the growth and apoptosis of human lens epithelial (HLE) B3 cells exposed to H2O2 was investigated. In addition, the effect of ginsenosides on gene expression in HLE-B3 cells was analyzed using microarray assays to determine its molecular mechanism.MethodsHLE-B3 cells were treated with 1.75 M H2O2 in the presence or absence of 5, 10 or 20 μM ginsenosides. Cell viability and apoptosis were examined by MTT assays and flow cytometry, respectively, at 24 to 120 h after the treatment. Furthermore, HLE-B3 cells were treated with 20 μM ginsenosides for 8 days and total RNA was isolated and analyzed using the Affymetrix GeneChip Array. Principal component analysis was performed to visualize the microarray data.ResultsAddition of ginsenosides significantly alleviated the growth inhibitory effect of H2O2 on HLE-B3 cells and the percentage of viable cells was increased by more than 3 folds. Flow cytometric analysis showed that 6.16 ± 0.29% of H2O2-treated HLE-B3 cells were early apoptotic cells, and the percentage was reduced to 4.78 ± 0.16% (P < 0.05) in the presence of 20 μM ginsenosides. Principal component analysis revealed that ginsenoside caused extensive changes in gene expression in HLE-B3 cells. A total of 6219 genes showed significant differential expression in HLE-B3 cells treated with ginsenoside; among them, 2552 (41.0%) genes were significantly upregulated, whereas 3667 (59.0%) genes were significantly downregulated. FOXN2, APP and RAD23B were the top three upregulated genes while WSB1, PSME4 and DCAF7 were the top three downregulated genes in HLE-B3 cells treated with ginsenosides.ConclusionGinsenosides induce extensive changes in the expression of genes involved in multiple signaling pathways, including apoptotic signaling pathway and DNA damage response signaling pathway. Ginsenosides alleviate H2O2-induced suppression of the growth of HLB cells and inhibit H2O2-induced apoptosis of HLB cells.

Highlights

The effect of ginsenosides on the growth and apoptosis of human lens epithelial (HLE) B3 cells exposed to Hydrogen peroxide (H2O2) was investigated
We investigated the effect of ginsenosides on the growth and apoptosis of human lens epithelial (HLE-B3) cells exposed to H2O2
Ginsenoside reverses H2O2-induced growth inhibition of HLE-B3 cells MTT assays showed that H2O2 exhibited a dosedependent inhibitory effect on the viability of HLE-B3 cells

Summary

Introduction

The effect of ginsenosides on the growth and apoptosis of human lens epithelial (HLE) B3 cells exposed to H2O2 was investigated. Hydrogen peroxide (H2O2), a non-free radical member of the active oxygen family, is the major intracellular reactive oxygen species (ROS) in the aqueous humor, which generates hydroxyl radicals that irreversibly damage the lens epithelium. It can activate multiple signaling events such as the activation of apoptosis-associated molecules or pathways, including caspases, the Bcl-2 family, the mitogen-activated protein kinases (MAPKs), and NF-кB pathways, which lead to apoptosis of lens epithelial cells (HLE), resulting in lens opacification and subsequent cataract development [7, 8]. A variety of antioxidant nutrients, such as flavonoids, phenolic acids, carotenoids, and vitamins, have been tested for their ability to prevent or delay cataract development in animal studies, but their protective effects have not been demonstrated unequivocally [9]

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