Network pharmacology predicted HDAC6 as a potential target of flavones from Daphne giraldii on hepatocellular carcinoma

Abstract

Daphne giraldii Nitsche, belongs to Daphne genus, has been reported to exert anti-tumor activities. Our previous study suggested that flavones from Daphne giraldii have significant inhibitory effects on hepatocellular carcinoma (HCC) cells. However, the potential target of this type flavone was still unknown. In this study, 74 flavonoids compounds of Daphne giraldii and 41 potential targets of HCC were analyzed by the network, the most potential target was histone deacetylase 6 (HDAC6). Considering the cytotoxicity, compound 70 (Daphnegiravone D, DGD) was chosen for further confirmation. Molecular docking study revealed that DGD formed high binding affinity with HDAC6. Concomitantly, pharmacological studies indicated that DGD could inhibit the expression of HDAC6 in vitro and in vivo. In this study, network pharmacology along with experimental validation predicted and verified HDAC6 as one of potential targets of flavones, these investigations provide a new insight for further study of Daphne giraldii on HCC treatment.

Graphical Abstract

Keywords:

• Daphne giraldii
• hepatocellular carcinoma
• flavone
• network pharmacology
• histone deacetylase 6

Disclosure statement

The authors have declared that there is no conflict of interest.

Additional information

Funding

This study was financially supported by National Nature Science Foundation of China [grant numbers 81973528, 81872766, 81673324, 81573319], China Postdoctoral Science Foundation [grant number 2017M620104].