Study on the Potential Molecular Mechanism of Kaempferol from Siraitia Grosvenorii in Inhibiting HepG2 Cell Proliferation
KE Feiyan1,2, ZHANG Dingguo1, LUO Guizhao1, WU Zhiwei1,2*
Exploring the potential molecular mechanism of Siraitia grosvenorii in inhibiting HCC (hepatocellular carcinoma) by network pharmacology molecular docking combined with cell experiment. The TCMSP database was used to screen the active components and targets of Siraitia grosvenorii, and the Genecards database was used to search the relevant targets of hepatocellular carcinoma. The potential targets of Siraitia grosvenorii for the treatment of hepatocellular carcinoma were obtained by intersection of these two targets on the Venny platform. DAVID database was used to enrich analysis for gene function and their working pathways (GO/KEGG) of potential action targets, and the “drug component-disease-target” and “drug component-target-pathway-disease” network maps of Momordica grosvenorii for the treatment of hepatocellular carcinoma were established by Cytoscape software. The core targets were obtained through the database of biological molecular function annotation system and the software of Cytoscape. Molecular docking between proposed drug active products (kaempferol) and key targets was performed in AutoDock Vina software. Using naphthol as the experimental drug and HepG2 as the research object, CCK-8 method was used to screen the concentration of kaempferol inhibiting HepG2 cell proliferation; flow cytometry was used to detect the apoptosis rate, and Western blot was used to analyze protein levels of potential targets identified through screening. Totally 11 active components and 77 related targets of Siraitia grosvenorii and 7 773 disease targets of hepatocellular carcinoma and 62 common targets were screened. Totally 275 biological functions and 87 signal pathways were obtained by functional enrichment analysis of GO and KEGG. Ten potential core targets of Siraitia grosvenorii for the treatment of hepatocellular carcinoma were screened, such as p65, JNK1, Caspase-3 and AKT1. Kaempferol above 20 μg/mL could significantly reduce the proliferation activity of HepG2 cells, increase its apoptosis rate, and significantly up regulate p65, Caspase-3 expression levels and down regulate JNK1 and AKT1 expression levels in HepG2 cells. Kaempferol isolated from Siraitia grosvenorii has the activity in inhibiting the proliferation and promoting apoptosis of liver cancer cells. However, Siraitia grosvenorii has the efficacy and characteristics of multi-component, multi-target, and multi-pathway, which reveals that the mechanism of Siraitia grosvenorii in the treatment of hepatocellular carcinoma is more complex.
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