Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

Abstract

Ethnopharmacological relevanceAcanthopanax senticosus (Rupr. & Maxim.) Harms (AS) has been used as a traditional medicine for the treatment of hypertension, rheumatism, ischemic heart disease, diabetes, and hepatitis in East Asia. This herb has been reported to possess anti-cancer, anti-diabetes, and anti-inflammatory properties. Aim of the studyTo examine the anti-inflammatory activity of AS extract (ASE) and its mechanism of action in Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS)-stimulated macrophages. Materials and methodsP. gingivalis LPS was used to induce an inflammatory response in the murine macrophage cell line RAW 264.7. Pro-inflammatory cytokines were measured by using an enzyme-linked immunosorbent assay. We used western blot assays and real-time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. Nuclear translocation of nuclear factor (NF)-κB was assessed by confocal microscopy. ResultsASE significantly induced the expression and activity of heme oxygenase-1 (HO-1), which is known to produce an anti-inflammatory effect, in RAW 264.7 cells, through NF-E2-related factor 2 (Nrf-2), Janus kinase, and extracellular signal-regulated kinase activation. ASE also effectively suppressed the production of pro-inflammatory cytokines, tumor necrosis factor α, interleukin (IL)-1β, and IL-6, and decreased the nuclear translocation and transactivity of activator protein-1 (AP-1) and NF-κB by inhibiting the phosphorylation of IκB-α in P. gingivalis LPS-stimulated macrophage cells. Furthermore, ASE inhibits signal transducer and activator of transcription (STAT)1 phosphorylation while it activates STAT3 phosphorylation in P. gingivalis LPS-stimulated RAW 264.7 cells. ConclusionsOur study suggests that ASE produces anti-inflammatory effects on P. gingivalis LPS-stimulated macrophages through a reduction in AP-1 and NF-κB activity, modulation of STAT1 and STAT3 phosphorylation, and upregulation of HO-1 expression through the activation of mitogen-activated protein kinase and Nrf-2 signaling pathways. Therefore, ASE could be a candidate for the prevention and treatment of periodontal diseases that involve excessive inflammation.