Skipjack tuna ( Katsuwonus pelamis ) eyeball oil exerts an anti-inflammatory effect by inhibiting NF-κB and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice

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: Introductionmentioning

confidence: 99%

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

Jiang

et al. 2016

IJMS

“…Another point is that the phosphorylation of MAP kinases is inhibited by LDHA inhibition. In the immune system, MAP kinases including ERK, JNK, and p38 play an important role in cytokine production, which is a cellular response (23). Cytokines increase the levels of leukocyte adhesion molecules that induce leukocyte extravasation (24).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of lactate dehydrogenase A suppresses inflammatory response in RAW 264.7 macrophages

Song

Kim

et al. 2018

Mol Med Report

Lactate is an important metabolite in cellular metabolism and fluctuates in certain disease conditions including cancer and immune diseases. It was hypothesized that a decrease in lactate would modulate the inflammatory response elicited by lipopolysaccharides (LPS) in macrophages. When RAW 264.7 macrophages were treated with FX11, a specific lactate dehydrogenase (LDHA) inhibitor, the expression of the cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) was downregulated due to reduced cellular lactate levels. Genetic suppression of LDHA by small interfering RNA (siRNA) downregulated the LPS-activated expression of interleukin (IL)-6, iNOS, and COX-2, and reduced the production of IL-6 and nitrites. Pharmacological and genetic suppression of LDHA inhibited the phosphorylation of p38 mitogen-activated protein kinase. Microarray gene expression profile demonstrated that the genes involved in cell proliferation and inflammation were mainly altered by siRNA-mediated LDHA suppression. Collectively, the present observations suggest that lactate may be an important metabolite and implicated in regulation of inflammatory response.

“…However, this conversion may not achieve EPA levels adequate for anti-inflammatory effects. Previous observational studies strongly support the efficacy of the marine-based n-3 PUFA such as DHA for preventing inflammation [29]. It has been reported particularly that DHA mediate its anti-inflammatory via the NFκB signaling system in a macrophage study [7].…”

Section: Effects Of Sda On Cellular Fatty Acid Profile In Lps-stimulamentioning

confidence: 93%

Anti‐Inflammatory Effects of Stearidonic Acid Mediated by Suppression of NF‐κB and MAP‐Kinase Pathways in Macrophages

Sung

Jeon²,

Kim

et al. 2017

Lipids

Stearidonic acid (SDA, 18:4n-3) is an omega-3 polyunsaturated fatty acid present in oils derived from plants of the Boraginaceae family. In this study, we determined the anti-inflammatory effects of SDA isolated from echium oil on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. SDA significantly downregulated the levels of the inducible nitric oxide synthase (iNOS) protein, thereby suppressing the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. In addition, SDA inhibited the nuclear translocation and promoter activity of nuclear factor κB (NFκB) and the phosphorylation of mitogen-activated protein kinases (MAPK) such as extracellular signal regulated kinase 1/2, c-jun N terminal kinase, and p38 in LPS-stimulated RAW 264.7 cells. Our results showed that SDA exerted anti-inflammatory effects by suppressing iNOS-mediated NO production via inactivation of NFκB and MAPK signaling pathways.