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

摘要

BackgroundInflammation is an essential component of liver diseases. Paeoniflorin (PF), a monoterpenoid component derived from peony root (Paeonia lactifloraPall.), 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.MethodsLPS 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.ResultsIn 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.ConclusionThese 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.