• Biomedical Science Letters
• /
• v.17 no.3
• /
• pp.225-230
• /
• 2011

Indirubin is the active ingredient of Danggui Longhui Wan, a mixture of plants that is used in traditional Chinese medicine to treat chronic diseases. In this study we investigated the anti-inflammatory effects of an indirubin derivative, indirubin-3’-monoxime-5-sulphonic acid (I3M-5S, $C_{16}H_{11}N_3O_5S$). We found that I3M-5S inhibits the production of various inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) as well as inflammatory cytokines, tumor necrosis factor-${\alpha}$ and interleukin-6 in lipopolysaccharide (LPS) stimulated murine macrophage, RAW264.7 cells. In addition, the expression of inducible nitric oxide synthase and cyclooxygenase-2, which are essential enzymes to produce NO and $PGE_2$, respectively, was blocked by I3M-5S treatment in LPS-stimulated RAW264.7 cells. Present data suggest that I3M-5S exhibits potent anti-inflammatory activity in cultured macrophages and merit further study as potential therapeutic agents for inflammatory disorders.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.28 no.3
• /
• pp.1-13
• /
• 2015

Objective : This study investigated the inflammatory reaction is characterized by over production of inflammatory mediators due to an up-regulation of inflammatory pathways.Methods : We investigated the anti-inflammatory effects of water extracts fromLonicera japonicaandScutellaria baicalensisin lipopolysaccharide (LPS)-stimulated U937 cells. Each extract suppressed the production of inflammatory mediators (NO, IL-1${\beta}$, TNF-${\beta}$, and PGE₂) and the expression of inducible NO synthase and cyclooxygenase-2 in LPS- stimulated U937 cells in a dose-dependent manner.Results : These suggest that the suppression effects were synergistically increased by their combination. Their combination extract also inhibited NF-${\kappa}B$-DNA complex of NF-${\kappa}B$ binding activity and translocation of NF-${\kappa}B$ from cytosol to nucleus.Conclusions : Our study suggest that the combination of water-extractable components ofL. japonicaandS. baicalensismay be useful for therapeutic drugs against inflammatory immune diseases, probably by suppressing the production of inflammatory mediators.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.1
• /
• pp.151-159
• /
• 2019

Lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of $TNF-{\alpha}$ and interleukin (IL)-6. In addition, pLTA increases the survival rate of mice in a septic shock model. In the current study, we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail, pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However, $TNF-{\alpha}$ production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and $TNF-{\alpha}$ induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA, but not by other LTAs isolated from either Staphylococcus aureus (aLTA) or L. sakei (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and $TNF-{\alpha}$ induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK), respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together, our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.

• Nutrition Research and Practice
• /
• v.11 no.4
• /
• pp.265-274
• /
• 2017

BACKGROUND/OBJECTIVES: Nelumbo leaves have been used in traditional medicine to treat bleeding, gastritis, hemorrhoids, and halitosis. However, their mechanisms have not been elucidated. MATERIALS/METHODS: The present study prepared two Nelumbo leaf extracts (NLEs) using water or 50% ethanol. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 and nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) productions were assessed. To determine the anti-inflammatory mechanism of NLEs, we measured nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity. Major metabolites of NLEs were also analyzed and quantified. RESULTS: NLEs effectively reduced the expression and productions of pro-inflammatory mediators such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, $PGE_2$, and NO. NLEs also reduced NF-${\kappa}B$ activity by inhibiting inhibitor of NF-${\kappa}B$ phosphorylation. Both extracts contained catechin and quercetin, bioactive compounds of NLEs. CONCLUSIONS: In this study, we showed that NLEs could be used to inhibit NF-${\kappa}B$-mediated inflammatory responses. In addition, our data support the idea that NLEs can ameliorate disease conditions involving chronic inflammation.

• The Journal of Pediatrics of Korean Medicine
• /
• v.36 no.3
• /
• pp.19-34
• /
• 2022

Objectives To investigate the effect of Jakyakgamcho-tang (JGT) on Dextran sulfate sodium (DSS) induced ulcerative colitis. Methods Experimental animals were divided into six groups; group 1, normal group; group 2, DSS-induced colitis group; group 3, 5-aminosalicylic acid (5-ASA)-treated group; group 4, Glycyrrhiza Uralensis (Gamcho, GC)-treated group; group 5, Paeoniae Radix (Jakyak, JY)-treated group; group 6, JGT-treated group. Inflammatory cytokines and their metabolites were detected. Result In the JGT group, the levels of tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) were significantly decreased, whereas that of Interleukin-10 (IL-10) were significantly increased. In addition, the metabolite profile changed in the JGT group with most metabolites increasing. Conclusion This study demonstrates that the therapeutic potential of JGT in ulcerative colitis. Further studies should be conducted to confirm our findings.

• Mycobiology
• /
• v.43 no.3
• /
• pp.319-326
• /
• 2015

Fomes fomentarius is a fungus of the Polyporaceae family and is used in traditional oriental therapies. Although the anti-inflammatory activities of this species have been previously reported, the identity of the bioactive compounds responsible for this activity remains unknown. Here, we investigated whether methyl 9-oxo-(10E,12E)-octadecadienoate (FF-8) purified from F. fomentarius exerts anti-inflammatory activity in murine macrophages stimulated with lipopolysaccharide (LPS). FF-8 suppressed secretion of nitric oxide (NO) and prostaglandin $E_2$ through downregulation of inducible NO synthase and cyclooxygenase-2 expression induced by LPS. In addition, pretreatment of cells with FF-8 led to a reduction in levels of secreted inflammatory cytokines such as tumor necrosis factor-${\alpha}$ and interleukin-6 in macrophages stimulated with LPS. Conversely, FF-8 did not affect nuclear factor ${\kappa}B$, p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase pathways. Instead, FF-8 specifically interfered with signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by LPS. Collectively, this study demonstrated that FF-8 purified from F. fomentarius suppresses inflammatory responses in macrophages stimulated with LPS by inhibiting STAT3 activation. Further studies will be required to elucidate the anti-inflammatory effect of FF-8 in vivo.

• Journal of Korean Medicine Rehabilitation
• /
• v.24 no.4
• /
• pp.15-28
• /
• 2014

Objectives This study was carried out to find out the Antioxidant and Anti-inflammatory Effects of Components of Mahwangbujaseshin-tang in LPS-Stimulated RAW264.7 Macrophages. Methods There are 5 experimental groups. ; normal, control, EH (Ephedrae Herba), ALRP (Aconiti Lateralis Radix Preparata) and AR (Asiasari Radix). The extract of EH, ALRP and AR ($100{\mu}g/ml$) was added to each group. We examined cytotoxicity, total phenolic contents, DPPH and ABTS free radical scavenging activity, Intracellular ROS (reactive oxygen species) production, NO (Total Nitric oxide), iNOS (inducible nitric oxide synthase), PGE2 (prostaglandin E2), COX-2 (cyclooxygenase-2), $IL-1{\beta}$ ($interleukin-1{\beta}$), IL-6 (interleukin-6), $TNF-{\alpha}$ (tumor necrosis factor-${\alpha}$), MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinase-1) and HO-1 (heme oxygenase-1) expression level. Results 1. Total phenolic contents of EH were in the highest level. 2. DPPH and ABTS free radical scavenging activity of EH was in the highest level. 3. ROS production was significantly decreased in AR. 4. NO production was significantly decreased in EH, ALRP, AR and iNOS expression was decreased in EH, AR. 5. PGE2 and COX-2 expression was decreased in EH, AR. 6. $IL-1{\beta}$ production was significantly decreased in EH, AR and IL-6 production was significantly decreased in AR. $TNF-{\alpha}$ production was significantly decreased in ALRP, AR. 7. MMP-9 and TIMP-1 production were significantly decreased in EH. 8. HO-1 expression was significantly increased in EH. 9. With simultaneous usage of SnPP which is expression inhibitor of HO-1, NO, $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production were partially increased in EH, ALRP, AR. Conclusions According to this study, Components of Mahwangbujaseshin-tang have anti-oxidants and anti-inflammation effects in LPS-Stimulated RAW264.7 Macrophages.

• Korean Journal of Medicinal Crop Science
• /
• v.17 no.2
• /
• pp.109-114
• /
• 2009

Rhubarb is the well-known and frequently used herbal medicine for the treatment of constipation, inflammation, and cancer. As described in the Korea and Chinese Pharmacopoeia, rhubarb consists of the roots and rhizomes of Rheum palmatum, R. officinale, and R. tanguticum. However, the pharmacological differences among rhubarb have not been scientifically established. In the present study, we investigated and compared the inhibitory effects of 70% ethanolic extracts from R. palmatum (RPE), R. officinale (ROE), R. nobile (RNE), and R. franzenbachii (RFE) on the production of inflammatory mediators, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), interlukin-1beta ($IL-1{\beta}$), and tumor necrosis factor-alpha ($TNF-{\alpha}$) in RAW 264.7 macrophage cells. ROE, RNE, and RFE significantly inhibited the release of NO, $PGE_2$, $IL-1{\beta}$, and $TNF-{\alpha}$. RPE significantly reduced the release of $IL-1{\beta}$, but not NO, $PGE_2$, and $TNF-{\alpha}$. Overall, RFE was found to inhibit the release of $PGE_2$ and $IL-1{\beta}$, to a far greater degree than RPE, ROE, and RNE. Our results indicate that RFE possess the strongest anti-inflammatory activity among 4 tested rhubarb.

• IMMUNE NETWORK
• /
• v.7 no.1
• /
• pp.31-38
• /
• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• The Korea Journal of Herbology
• /
• v.34 no.6
• /
• pp.117-124
• /
• 2019

Objective : Broccoli is edible green plant that has a wide variety of health benefits including cancer prevention and cholesterol reduction. However, leaves of broccoli are not eaten and are mostly left as waste. This study was conducted to evaluate the effects of the broccoli leaf extract (BLE) on prostaglandin E₂ (PGE₂) production related to nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-activated macrophages. Methods : BLE was prepared by extracting dried leaf with ethanol. Cell viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PGE₂ and inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Expression level of each protein was monitored by Western blot analysis. Results : In LPS-activated Raw264.7 cells, PGE₂ release into culture medium was dramatically enhanced compared to control cells. However, increased PGE₂ was attenuated dose-dependently by treatment with BLE. Inhibition of PGE₂ production by BLE was due to the suppression of cyclooxygenase-2 (COX-2) expression determined by Western blot analysis. BLE also inhibited the production of inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Inhibition at PGE₂ and cytokine was mediated from inhibition of nuclear translocation of NF-κB due to the repression of inhibitory kappa B alpha (IκBα) phosphorylation and degradation. Conclusion : This study showed that BLE exerted inhibitory activities against PGE₂, which is critical for the initiation and resolution of inflammatory responses, and that inhibition of PGE₂ was mediated by suppression of NF-κB signaling. These results suggest that the waste broccoli leaves could be used for controlling inflammation.