Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-κB and JNK/p38 MAPK

Jiang

et al. 2016

IJMS

Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells

Jiang

et al. 2016

IJMS

“…NF-κB and MAPK, served as the major transcription factors, have been reported to play vital roles in the regulation of inflammatory cytokines production 29, 30 . Generally, once stimulated, NF-κB activation is initiated by the IκB-α and then NF-κB p65 is translocated to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of TM6 on LPS-induced acute lung injury in mice

Tian

et al. 2017

Sci Rep

Acute lung injury (ALI) is an acute failure of the respiratory system for which effective treatment is urgently necessary. Previous studies found that several peptides potently inhibited the production of cytokines induced by lipopolysaccharide (LPS). In this study, we synthetized a cell-permeable TIR domain-derived decoy peptide (TM6) and examined its substance for the ability to inhibit TLR signaling in the model of ALI induced by LPS. We demonstrated that TM6 (2.5, 5 and 10 nmol/g) alleviated the histological changes in the lung tissues as well as myeloperoxtidase (MPO) activity, lung W/D ratio, the production of TNF-α, IL-1β and IL-6 induced by LPS. Furthermore, the numbers of total cells, neutrophils and macrophages in the BALF were suppressed by TM6. In vitro, TM6 (5, 10 and 20 µM) inhibited the production of TNF-α, IL-1β and IL-6 in LPS-stimulated alveolar macrophages. Moreover, the activation of Nuclear factor-kappaB (NF-κB) and Mitogen activated protein kinases (MAPK) signaling pathways induced by LPS were also inhibited by TM6. Collectively, our results suggested that TM6 was an effective inhibitor of ALI induced by LPS, and this peptide may very well serve as a future treatment for ALI.

Journal of Periodontology

“…The MAPK‐mediated pathway is another vital signaling pathway involved in LPS‐induced inflammation 4 . As a new member of the MAPK family, the role of ERK5 in inflammatory response has attracted much attention 24 , 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Lipopolysaccharide (LPS), a major component of the outer membrane of Gram‐negative bacteria, 3 plays a crucial role in the development of periodontal disease. It stimulates host cells and initiates proinflammatory signaling pathways such as the nuclear factor (NF)‐kappa B and mitogen‐activated protein kinase (MAPK) pathways, resulting in excessive expression and secretion of a large number of proinflammatory cytokines 4 , 5 . Destruction of periodontal tissue has been associated with overexpression of these cytokines 6 …”

mentioning

confidence: 99%

The Proteasome Inhibitor Bortezomib Inhibits Inflammatory Response of Periodontal Ligament Cells and Ameliorates Experimental Periodontitis in Rats

Jiang

Song

et al. 2017