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

• Published in: Purinergic signalling 2024-08, Vol.20 (4), p.449-463
• Main Authors: Zhang, Zhenglang, Wang, Tingting, Luo, Zhenhui, Zaib, Muhammad Haris, Yi, Mengqin, Zeng, Hekun, Li, Peiyang, Tang, Dan, Verkhratsky, Alexei, Nie, Hong
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics - pharmacology; Animals; Anti-Inflammatory Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Dorsal root ganglia; Extracellular signal-regulated kinase; Human Physiology; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Interleukin 6; Interleukin 8; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred C57BL; Network Pharmacology; Neurosciences; Pain; Pain - drug therapy; Pain - metabolism; Pharmacology/Toxicology; Phosphorylation; RAW 264.7 Cells; Receptors, Purinergic P2X7 - drug effects; Receptors, Purinergic P2X7 - metabolism; Sequence Analysis, RNA - methods; Signal transduction
• ISSN: 1573-9538; 1573-9546; 1573-9546
• DOI: 10.1007/s11302-023-09979-2

Inflammatory pain, sustained by a complex network of inflammatory mediators, is a severe and persistent illness affecting many of the general population. We explore possible anti-inflammatory pathways of Polyphyllin VI (PPVI) based on our prior study, which showed that PPVI reduces inflammation in mice to reduce pain. Network pharmacology and RNA-Seq identified the contribution of the MAPK signaling pathway to inflammatory pain. In the LPS/ATP-induced RAW264.7 cell model, pretreatment with PPVI for 1 h inhibited the release of IL-6 and IL-8, down-regulated expression of the P2X 7 receptor(P2X 7 R), and decreased phosphorylation of p38 and ERK1/2 components of the MAPK pathway. Moreover, 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 while the reductions of expression of IL-6 and phosphorylation of ERK1/2 were not observed after the pre-treatment with A740003 (an antagonist of the P2X 7 R). These results suggest that PPVI may inhibit the release of IL-8 by regulating P2X 7 R to reduce the phosphorylation of p38. However, the modulation of PPVI on the release of IL-6 and phosphorylation of ERK1/2 may mediated by other P2X 7 R-independent signals. Graphical Abstract