Paeoniflorin inhibits lipopolysaccharide-induced inflammation in LO2 cells by regulating RhoA/NLRP3 pathway

Abstract

Inflammation is an essential component of liver diseases. Paeoniflorin (PF), a monoterpenoid component derived from peony root ( Paeonia lactiflora Pall.), has anti-inflammatory, immunoregulatory, and hepatoprotective activities. However, whether PF affects liver inflammation and its underlying mechanisms is unclear. In this study, we investigated the effects of PF on lipopolysaccharide (LPS)-induced inflammation in LO2 cells and the underlying molecular mechanism. LPS was used to induce inflammation. After PF pretreatment for 2 h, the cells were treated with PF and LPS. Cell counting kit-8 was used to measure cell viability. Tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were tested by Enzyme-linked immunosorbent assay. Western blot was used to evaluate TNF-α, Ras homolog family member A (RhoA), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1β proteins expression. In LPS-induced LO2 cells, PF reduced TNF-α and IL-6 inflammatory cytokine production in a dose-dependent manner. LPS-induced TNF-α expression was also suppressed by PF. In addition, PF significantly inhibited LPS-induced RhoA activation ( P = .0014). Finally, PF suppressed LPS-induced NLRP3 inflammasome activation by downregulating NLRP3, ASC, caspase-1, and IL-1β expression. These findings suggest that PF alleviates inflammation induced by LPS and further suggest the anti-inflammatory effect of PF may follow via reduced RhoA and NLRP3 inflammasome activity.