Effect and Mechanism of Schizandrin A in the Treatment of Liver Cancer Using Network Pharmacology, Molecular Docking, and Target Validation

Abstract

Background Liver cancer is a common threat to human health. Schizandrin A (SA) has certain therapeutic effect on liver cancer, but its related mechanism of action is not clear. Elucidating this mechanism is of great significance for the development of drugs to target liver cancer. Objective The objective is to study the effect and mechanism of SA on liver cancer. Methods The potential targets of SA in the treatment of liver cancer were screened based on network pharmacology, and the core targets were further screened by protein network interaction. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed based on the core targets to find the key pathways of action. The results obtained for key targets and pathways were verified in vitro by pharmacological experiments with HepG2 cells. Specifically, an Enzyme Linked Immunosorbent assay (ELISA) kit was used to detect the content of key indicators (interleukin-1 (IL-1), Tumor Necrosis Factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase [SOD], malondialdehyde [MDA], interferon (IFN), and Glutathione peroxidase (GSH-px)), Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to detect the key messenger Ribonucleic Acid (mRNA) (phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), vascular endothelial growth factor A (VEGFA), and Transforming Growth Factor Beta-1 (TGF-β1)) after drug intervention, and Western blotting (WB) detected the expression of key target proteins (p-PI3K, PI3K, p-Akt, and Akt). Results The results showed that SA mainly acts on IL-1β, TNF-α, IL-6, IL-10, SOD, MDA, TGF-β1, IFN, and VEGFA, affecting the PI3K-Akt signaling pathway and playing an anti-inflammatory role in the treatment of liver cancer. The experimental results showed that SA significantly reduced the inflammation level of HepG2 cells; improved the oxidative stress state (decreasing SOD level and increasing MDA level of cells); downregulated TGF-β1, VEGFA, PI3K, and Akt mRNA levels; and inhibited the expression of the PI3K-Akt signaling pathway. Conclusions SA has a significant anti-HepG2 effect, which may be achieved by reducing inflammation levels, improving oxidative stress state, and inhibiting the PI3K-Akt pathway.

The therapeutic effect of ultrasound targeted destruction of schisandrin A contrast microbubbles on liver cancer and its mechanism

“… 12 Our previous study found that Schisandrisin A significantly reduced the inflammation level of HepG2 cells; improved the oxidative stress state; downregulated transforming growth factor beta 1 (TGF-β1), vascular endothlial growth factor (VEGF), phosphoinositide 3-kinase (PI3K), and Akt mRNA levels; inhibited the expression of the PI3K-Akt signaling pathway, and had a significant anti-tumor effect on tumor cells with high activity and small molecular weight, which was an ideal candidate for the production of contrast-enhanced ultrasound microbubbles. 13 Therefore, in this study, Schisandin A was loaded into Span-PEG microbubbles to make ultrasound contrast agent and to play an anti-tumor effect on the lesions of liver cancer, which was rarely reported. This study would provide a new reference for the treatment of liver cancer.…”