Anti-inflammatory and analgesic properties of Polyphyllin VI revealed by network pharmacology and RNA sequencing

Abstract

Inflammatory pain, sustained by a complex network of inflammatory mediators, is a severe and persistent illness affecting a large proportion of the general population. Based on our earlier research showing that Polyphyllin VI (PPVI) alleviates pain by reducing inflammation in mice we proceed to identify potential anti-inflammatory mechanisms of PPVI. Network pharmacology and RNA-Seq identified the contribution of the MAPK signaling pathway to inflammatory pain. In the in vitro LPS/ATP-induced RAW264.7 cell model pretreatment with PPVI for 24h inhibited the release of IL-6、IL-8, down-regulated expression of the P2X7 receptor(P2X7R), and decreased phosphorylation of p38 and ERK1/2 components of the MAPK pathway. Similarly, PPVI decreased expression of IL-6 and IL-8 was observed in the serum of the inflammatory pain mice model and reduced phosphorylation of p38 and ERK1/2 in the dorsal root ganglia. These results suggest that PPⅥ reduces phosphorylated p38 and ERK1/2 by regulating P2X7R, thus inhibiting the release of IL-6 and IL-8 to alleviate inflammatory pain.