Abstract: PURPOSE: To investigate the potential mechanisms of scutellarin on oral leukoplakia (OLK) by network pharmacology and further verify by cytology. METHODS: The potential targets of scutellarin acting on OLK were excavated through network pharmacology. PPI network was constructed, and the possible targets and pathways of scutellarin were predicted by GO and KEGG enrichment analysis. CCK-8 and Transwell assays were used to verify the effects of scutellarin on proliferation, migration and invasion of Leuk-1 and Cal-27 cell lines. The expression of related molecules was detected by Western blot to explore potential molecular mechanisms. Statistical analysis was performed with GraphPad Prism 9 software package. RESULTS: There were 29 potential targets of scutellarin acting on OLK, of which HIF-1α was the key target, and the results of GO and KEGG analysis showed that scutellarin was highly involved in the response of cells and tissues to hypoxia and influenced HIF-1 signaling pathway. Scutellarin can significantly inhibit the proliferation (IC₅₀:2 mmol/L), invasion and migration of Leuk-1 and Cal-27 cells(P<0.05), and downregulated the expression of HIF-1α in Leuk-1 and Cal-27 cells. CONCLUSIONS: Scutellarin can inhibit carcinogenesis of OLK by suppressing HIF-1 signaling pathway.

Key words: Network pharmacology, Scutellarin, Oral leukoplakia, HIF-1α