scholarly journals Neolitsea Sericea Essential Oil Attenuates LPS-induced Inflammation in RAW 264.7 Macrophages by Suppressing NF-κB and MAPK Activation

2010 ◽  
Vol 5 (8) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Weon-Jong Yoon ◽  
Ji-Young Moon ◽  
Ji-Yong Kang ◽  
Gi-Ok Kim ◽  
Nam Ho Lee ◽  
...  

The chemical composition and antiinflammatory activities of hydrodistilled essential oil from Neolitsea sericea leaves (NSE) have been investigated for the first time. The chemical constituents of NSE were analysed by GC-MS and found to include sericenine (32.3%), sabinene (21.0%), trans-β-ocimene (13.3%), β-caryophyllene (4.8%), and 4-terpineol (4.2%). The effects of NSE on nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. Pro-inflammatory cytokine and mediator tests indicated that NSE has excellent dose-dependent inhibitory activities. To further examine the mechanism responsible for the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression by NSE, we examined the effect of NSE on nuclear factor-κB (NF-κB) activation and the phosphorylation of mitogen-activated protein kinases (MAPK). NSE inhibited NF-κB activation by LPS, and this was associated with the abrogation of IκB-α phosphorylation and subsequent decreases in nuclear p50 and p65 protein levels. Further, the phosphorylation of p38, ERK and JNK was suppressed by NSE in a concentration-dependent manner. These results suggest that NSE exerts antiinflammatory effects in LPS-stimulated RAW 264.7 macrophages by inhibition of NF-κB activation and MAPK phosphorylation, and, therefore, may be useful for treatment of inflammatory diseases.

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2092048 ◽  
Author(s):  
Hyun-Kyu Kang ◽  
Chang-Gu Hyun

Recently, additional therapeutic potentials of classical antibiotics are gaining considerable attention. The discovery of penicillin in the 1920s had a major impact on the history of human health. Penicillin has been used for the treatment for fatal microbial infections in humans and has led to the discovery of several new antibiotics. d-(+)-Cycloserine (DCS) is an antibiotic isolated from Streptomyces orchidaceous and is used in conjunction with other drugs in the treatment of tuberculosis. However, there have been no studies on the anti-inflammatory effects of DCS in RAW 264.7 macrophage cell line. To investigate the anti-inflammatory effects of DCS, we examined the ability of DCS to inhibit the inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in this study. Cell viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were pretreated with various concentrations (2, 4, and 6 mM) of DCS, then treated with 1 μg/mL LPS to detect its anti-inflammatory effects. d-(+)-Cycloserine inhibited the production of nitric oxide (NO) in a concentration-dependent manner, and to some extent, inhibited the production of prostaglandin E2. Consistent with these findings, DCS suppressed the expression of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6. However, it had no effect on the expression of tumor necrosis factor-α. Western blot analysis demonstrated that DCS inhibited inducible nitric oxide synthase and suppressed cyclooxygenase type-2 (COX-2) expression. In addition, investigation of its effects on nuclear factor kappa B signaling showed that DCS inhibited phosphorylation of inhibitory kappa B-α (IκB-α) and increased intracellular IκB-α in a concentration-dependent manner. Furthermore, DCS inhibited the phosphorylation of LPS-induced extracellular signal-regulated kinase, however it did not affect phosphorylation of c-jun N-terminal kinase and p38. Further studies confirmed that the inhibition of phosphorylation of IκB-α was mediated through the inhibition of phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway. To determine the applicability of DCS to the skin, cytotoxicity on HaCaT keratinocytes was measured following treatment with various concentrations (2, 4, 6, 8, and 10 mM) of DCS using MTT assay. These results suggest that DCS may be used as a potential drug for the treatment of inflammatory diseases.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hai Yang Yu ◽  
Kyoung-Sook Kim ◽  
Young-Choon Lee ◽  
Hyung-In Moon ◽  
Jai-Heon Lee

Oleifolioside A, a new triterpenoid compound isolated fromDendropanax morbiferaLeveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E2(PGE2) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-κB in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-αand subsequent translocation of the NF-κB p65 subunit to the nucleus. Inhibition of NF-κB activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.


2021 ◽  
Vol 22 (15) ◽  
pp. 8120
Author(s):  
Dahae Lee ◽  
Seoung Rak Lee ◽  
Ki Sung Kang ◽  
Ki Hyun Kim

The fruits of the mulberry tree (Morus alba L.), known as white mulberry, have been consumed in various forms, including tea, beverages, and desserts, worldwide. As part of an ongoing study to discover bioactive compounds from M. alba fruits, the anti-inflammatory effect of compounds from M. alba were evaluated in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. Phytochemical analysis of the ethanol extract of the M. alba fruits led to the isolation of 22 compounds. Among the isolated compounds, to the best of our knowledge, compounds 1, 3, 5, 7, 11, 12, and 14–22 were identified from M. alba fruits for the first time in this study. Inhibitory effects of 22 compounds on the production of the nitric oxide (NO) known as a proinflammatory mediator in LPS-stimulated RAW 264.7 macrophages were evaluated using NO assays. Western blot analysis was performed to evaluate the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5). We evaluated whether the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5) following LPS stimulation in RAW 264.7 macrophages occurred because of phosphorylation of IκB kinase alpha (IKKα), IκB kinase beta (IKKβ), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB) and activations of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cyclo(L-Pro-L-Val) (5) significantly suppressed phosphorylations of IKKα, IKKβ, IκBα, and NF-κB and activations of iNOS and COX-2 in a concentration-dependent manner. Taken together, these results indicate that cyclo(L-Pro-L-Val) (5) can be considered a potential therapeutic agent for the treatment of inflammation-associated disorders.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Soo Chil Lee ◽  
Young-Won Kwon ◽  
Ju-Yeon Park ◽  
Sung Yun Park ◽  
Ju-Hee Lee ◽  
...  

SC-E3 is a novel herbal formula composed of five oriental medicinal herbs that are used to treat a wide range of inflammatory diseases in Korean traditional medicine. In this study, we sought to determine the effects of SC-E3 on free radical generation and inflammatory response in lipopolysaccharide- (LPS-) treated RAW 264.7 macrophages and the molecular mechanism involved. The ethanol extract of SC-E3 showed good free radical scavenging activity and inhibited LPS-induced reactive oxygen species generation. SC-E3 significantly inhibited the production of the LPS-induced inflammatory mediators, nitric oxide and prostaglandin E2, by suppressing the expressions of inducible nitric oxide synthase and cyclooxygenase-2, respectively. SC-E3 also prevented the secretion of the proinflammatory cytokines, IL-1β, TNF-α, and IL-6, and inhibited LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Furthermore, SC-E3 induced the expression of heme oxygenase-1 (HO-1) by promoting the nuclear translocation and transactivation of Nrf2. Taken together, these results suggest that SC-E3 has potent antioxidant and anti-inflammatory effects and that these effects are due to the inhibitions of NF-κB and MAPK and the induction of Nrf2-mediated HO-1 expression in macrophages. These findings provide scientific evidence supporting the potential use of SC-E3 for the treatment and prevention of various inflammatory diseases.


Author(s):  
Adek Zamrud Adnan ◽  
Muhammad Taher ◽  
Tika Afriani ◽  
Annisa Fauzana ◽  
Dewi Imelda Roesma ◽  
...  

 Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.


2018 ◽  
Vol 13 (5) ◽  
pp. 1934578X1801300
Author(s):  
You Chul Chung ◽  
Sung-Min Park ◽  
Jin Hwa Kim ◽  
Geun Soo Lee ◽  
Jung No Lee ◽  
...  

The Trifolium pratense L. (red clover), which blossoms, leaves and stems can be used as medicines for treatment of burns, skin diseases, diabetes and other diseases. Recently study shown that pratol (7-hydroxy-4-methoxyflavone), an O-methylated flavone in T. pratense has been evaluated to induce melanogenesis in B16F10 melanoma cells. However, the anti-inflammatory effect of pratol has not been reported. In this study, we investigated the effects of pratol on anti-inflammation. We also studied the mechanism of action of pratol in LPS-stimulated RAW 264.7 cells. The cells were treated with various concentration of pratol (25, 50, or 100 μM) and 25 μM ammonium pyrrolidinedithiocarbamate (APDC) was used as control. The results in LPS-stimulated RAW 264.7 cells showed that pratol significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without any cytotoxic. In addition, pratol strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooygenase (COX-2). Furthermore, pratol reduced proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We also found that pratol strongly inhibited activation of nuclear factor kappa B (NF-κB) by reducing the p65 phosphorylation and protecting inhibitory factor kappa B alpha (IκBα) degradation. The results suggest that, pratol may be used to treat or prevent inflammatory diseases such as dermatitis, arthritis, cardiovascular and cancer.


2009 ◽  
Vol 2 (4) ◽  
pp. 245-249 ◽  
Author(s):  
Eun-Jin Yang ◽  
Eun-Young Yim ◽  
Gwanpil Song ◽  
Gi-Ok Kim ◽  
Chang-Gu Hyun

Inhibition of nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages by Jeju plant extractsNitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed during septic shock and inflammation. Thus, inhibitors of iNOS may be useful candidates for the treatment of inflammatory diseases accompanied by the overproduction of NO. In this study, we prepared alcoholic extracts of Jeju plants and screened them for their inhibitory activity against NO production in lipopolysaccharide (LPS)-activated macrophages. Among the 260 kinds of plant extract tested, 122 extracts showed potent inhibitory activity towards NO production by more than 25% at a concentration of 100 μg/mL. Plants such asMalus sieboldii, Vaccinium oldhamii, Corylus hallaisanensis, Carpinus laxiflora, Styrax obassia, andSecurinega suffruticosashowed the most potent inhibition (above 70%) at a concentration of 100 μg/mL. The cytotoxic effects of the plant extracts were determined by colorimetric MTT assays and most plant extracts exhibited only moderate cytotoxicity at 100 μg/mL. Therefore, these plants should be considered promising candidates for the further purification of bioactive compounds and would be useful for the treatment of inflammatory diseases accompanying overproduction of NO.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Eun-Jin Yang ◽  
Young Min Ham ◽  
Kyong-Wol Yang ◽  
Nam Ho Lee ◽  
Chang-Gu Hyun

During our ongoing screening program designed to determine the anti-inflammatory potential of natural compounds, we isolated sargachromenol fromSargassum micracanthum. In the present study, we investigated the anti-inflammatory effects of sargachromenol on lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells and the underlying mechanisms. Sargachromenol significantly inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E2(PGE2) in a dose-dependent manner. It also significantly inhibited the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner in LPS-stimulated macrophage cells. Further analyses showed that sargachromenol decreased the cytoplasmic loss of inhibitorκBα(IκBα) protein. These results suggest that sargachromenol may exert its anti-inflammatory effects on LPS-stimulated macrophage cells by inhibiting the activation of the NF-κB signaling pathway. In conclusion, to our knowledge, this is the first study to show that sargachromenol isolated fromS. micracanthumhas an effective anti-inflammatory activity. Therefore, sargachromenol might be useful for cosmetic, food, or medical applications requiring anti-inflammatory properties.


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