Chlojaponilactone B Attenuates Lipopolysaccharide-Induced Inflammatory Responses by Suppressing TLR4-Mediated ROS Generation and NF-κB Signaling Pathway.
Shaoxia YeQiyao ZhengYang ZhouBai BaiDepo YangZhi-Min ZhaoPublished in: Molecules (Basel, Switzerland) (2019)
The lindenane-type sesquiterpenoid chlojaponilactone B (1), isolated from Chloranthus japonicus, has been reported to possess anti-inflammatory properties. The present study aimed to further explore the molecular mechanisms underlying the anti-inflammatory activity of 1. RNA-seq analyses revealed the significant changes in the expression levels of genes related to multiple inflammatory pathways upon treatment of lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages with 1. Real time PCR (RT-PCR) and Western blotting were used to confirm the modulations in the expression of essential molecules related to inflammatory responses. Compound 1 inhibited toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) activation upon LPS stimulation, influencing the expression of NF-κB and pro-inflammatory mediators. Molecular docking studies showed that 1 bound to TLR4 in a manner similar to that of TAK-242, a TLR4 inhibitor. Moreover, our results showed that 1 suppressed inflammatory responses by inhibiting TLR4 and subsequently decreasing reactive oxygen species (ROS) generation, downregulating the NF-κB, thus reducing the expression of the pro-inflammatory cytokines iNOS, NO, COX-2, IL-6 and TNF-α; these effects were similar to those of TAK-242. We proposed that 1 should be considered as a potential anti-inflammatory compound in future research.
Keyphrases
- inflammatory response
- toll like receptor
- lps induced
- lipopolysaccharide induced
- nuclear factor
- signaling pathway
- poor prognosis
- anti inflammatory
- molecular docking
- reactive oxygen species
- rna seq
- immune response
- single cell
- oxidative stress
- pi k akt
- south africa
- real time pcr
- binding protein
- molecular dynamics simulations
- genome wide
- nitric oxide
- cell death
- gene expression
- climate change
- dna methylation
- risk assessment
- rheumatoid arthritis
- acute myeloid leukemia
- bone marrow
- single molecule
- dendritic cells
- cell proliferation
- nitric oxide synthase
- current status