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

  • Rungthip Thongboontho (Division of Biochemistry, School of Medical Sciences, University of Phayao) ;
  • Kanoktip Petcharat (Division of Biochemistry, School of Medical Sciences, University of Phayao) ;
  • Narongsuk Munkong (Department of Pathology, School of Medicine, University of Phayao) ;
  • Chakkraphong Khonthun (Division of Biochemistry, School of Medical Sciences, University of Phayao) ;
  • Atirada Boondech (Biology Program, Faculty of Science and Technology, Kamphaeng Phet Rajabhat University) ;
  • Kanokkarn Phromnoi (Division of Biochemistry, School of Medical Sciences, University of Phayao) ;
  • Arthid Thim-uam (Division of Biochemistry, School of Medical Sciences, University of Phayao)
  • Received : 2023.05.10
  • Accepted : 2023.05.19
  • Published : 2023.10.01

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 p2phox 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.

Keywords

Acknowledgement

This research was supported by grants from the Thailand Science Research and Innovation Fund and the University of Phayao (grant No.FF64-UoE020 for A.T.; grant No. RD61067 and RD62061 for R.T.; and grant No. UoE65005 for K.P.).

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