Effects of Pogonatherum paniceum (Lamk) Hack extract on anti-mitochondrial DNA mediated inflammation by attenuating Tlr9 expression in LPS-induced macrophages

Abstract

BACKGROUND/OBJECTIVES Mitochondrial DNA leakage leads to inflammatory responses via endosome activation. This study aims to evaluate whether the perennial grass water extract ( Pogonatherum panicum ) ameliorate mitochondrial DNA (mtDNA) leakage. MATERIALS/METHODS The major bioactive constituents of P. paniceum (PPW) were investigated by high-performance liquid chromatography, after which their antioxidant activities were assessed. In addition, RAW 264.7 macrophages were stimulated with lipopolysaccharide, resulting in mitochondrial damage. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to examine the gene expression and cytokines. RESULTS Our results showed that PPW extract-treated activated cells significantly decrease reactive oxygen species and nitric oxide levels by reducing the p22 phox and iNOS expression and lowering cytokine-encoding genes, including IL-6 , TNF-α , IL-1β , PG-E2 and IFN-γ relative to the lipopolysaccharide (LPS)-activated macrophages. Furthermore, we observed that LPS enhanced the mtDNA leaked into the cytoplasm, increasing the transcription of Tlr9 and signaling both MyD88 / Irf7- dependent interferon and MyD88/NF-κb p65-dependent inflammatory cytokine mRNA expression but which was alleviated in the presence of PPW extract. CONCLUSIONS Our data show that PPW extract has antioxidant and anti-inflammatory activities by facilitating mtDNA leakage and lowering the Tlr9 expression and signaling activation.