• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.6
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• pp.670-677
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• 2007

We analyzed antioxidant and physiological activities to investigate the functional effects of ethanol extracts of Anomala albopilosa imago and A. albopilosa larva. In order to effectively screen for anti-inflammatory agents, we first investigated the antioxidant activities such as DPPH radical scavenging capacity, superoxide radical scavenging capacity, xanthine oxidase inhibitory activity, and nitric oxide scavenging capacity of the A. albopilosa extracts. By the screening system, we found that A. albopilosa extracts had antioxidant activity which increased with increments of the extract concentration. Moreover, we examined the inhibitory effect of the A. albopilosa extracts on the production of anti-inflammatory factors that the nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostaglandin $E_2\;(PGE_2)$ production activated with LPS ($1{\mu}g/mL$) in murine macrophage cell line RAW 264.7. A. albopilosa extracts potentially inhibited the iNOS and COX-2 in a dose-dependent manner. The inhibition of iNOS activity was correlated with the decrease in nitrite levels. Additionally, the $PEG_2$ production is markedly inhibited after a treatment with the A. albopilosa extracts.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.305-310
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• 2005

It has been suggested that nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) may act as a mediator of cytokine-induced effects on bone turn-over. NO is also recognized as an important factor in bone remodeling, i.e., participating in osteoblast apoptosis in an arthritic joint. The components of Agastache rugosa are known to have many pharmacological activities. In the present study, we investigated the effects of Agastache rugosa leaf extract (ELAR) on NO production and the iNOS expression in ROS 17/2.8 cells activated by a mixture of inflammatory cytokines including TNF-$alpha$ and IL-1$\beta$. A preincubation with ELAR significantly and concentration-dependently reduced the expression of iNOS protein in ROS 17/2.8 cells activated with the cytokine mixture. Consequently, the NO production was also significantly reduced by ELAR with an IC$_{50}$ of 0.75 mg/mL. The inhibitory mechanism of iNOS induction by ELAR prevented the activation and translocation of NF-$\kappa$B (p65) to the nucleus from the cytosol fraction. Furthermore, ELAR concentration-dependently reduced the cellular toxicity induced by sodium nitroprusside, an NO-donor. These results suggest that ELAR may be beneficial in NO-mediated inflammatory conditions such as osteoporosis.

• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Journal of Life Science
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• v.25 no.9
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• pp.976-983
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• 2015

Achyranthoside C dimethyl ester (ACDE) is an oleanolic acid glycoside from Achyranthes japonica which has been used in traditional medicine for the treatment of edema and arthritis. In this study, we investigated the anti-inflammatory effects of ACDE in RAW264.7 macrophages. ACDE significantly induced heme oxygenase-1 (HO-1) gene expression in RAW264.7 cells, while ACDE improved LPS-induced toxicity of cells. And ACDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Further study demonstrated that ACDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) (LY294002), c-Jun kinase (JNK) (SP600125), extracellular signal regulated kinase (ERK) (PD98059) and p38 kinase (SB203580). Moreover, ACDE phosphorylated Akt, JNK, ERK, and p38 MAPK. In addition, ACDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression in a dose-dependent manner. The inhibitory effects of ACDE on iNOS expression were abrogated by small interfering RNA (siRNA)-mediated knock-down of HO-1. Therefore, these results suggest that ACDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/MAPK-Nrf2 signaling pathway. These findings could help us to understand the active principle included in the roots of A. japonica and the molecular mechanisms underlying anti-inflammatory action of ACDE.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5317-5324
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• 2014

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of cancer, but the results are still debatable. Therefore, we performed a systematic review to provide a more complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, EMBASE, EBSCO, Google Scholar and China National Knowledge Infrastructure (CNKI) databases until April 2014 to identify eligible studies. Thirty-one studies with cancer patients and controls were included in the meta-analysis. Overall, the polled analysis revealed that the T-786C polymorphism was significantly associated with increased cancer risk under multiple genetic models (C vs T: OR=1.135, 95%CI=1.048-1.228; CC vs TT: OR=1.278, 95%CI=1.045-1.562; TC vsTT: OR=1.136, 95%CI=1.023-1.261; CC+TC vs TT: OR=1.159, 95%CI=1.047-1.281; CC vs TC+TT: OR=1.204, 95%CI= 1.003-1.447). G894T was associated with significant risk for females (TT vs GG: OR=1.414, 95%CI=1.056-1.892; TT vs GT+GG: OR=1.356, 95%CI=1.108-1.661) and for breast cancer (T vs G: OR=1.097, 95%CI=1.001-1.203; TT vs GG: OR=1.346, 95%CI=1.012-1.789; TT vs GT+GG: OR=1.269, 95%CI=1.028-1.566). Increased susceptibility was revealed for prostate cancer with 4a/b (ba vs bb: OR=1.338, 95%CI=1.013-1.768; aa+ba vs bb: OR=1.474, 95%CI=1.002-2.170). This meta-analysis indicated that the eNOS T-786C polymorphism is associated with elevated cancer risk; the G894T polymorphism contributes to susceptibility to breast cancer and cancer generally in females; and the 4a/b polymorphism may be associated with prostate cancer risk.

• Journal of Life Science
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• v.18 no.12
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• pp.1651-1656
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• 2008

Redox factor-1 (Ref-1) is essential for repair of oxidatively damaged DNA and also govern the reductive activation of many transcription factors. In this study, we examined the effect of overexpressed Ref-1 on AKT activation for nitric oxide (NO) production in mouse aortic endothelial (MAE) cells. Adenoviral-mediated overexpression of Ref-1 enhanced NO production in unstimulated- as well as bradykinin-stimulated MAE cells. Importantly, forced overexpression of Ref-1 induced direct phosphorylation of AKT in cells. And, a PI3K inhibitor wortmannin completely abolished the increase in AKT phosphorylation by stimulation of bradykinin and/or overexpressed Ref-1. In addition, inhibition of AKT activity with HA-tagged activation-deficient AKT suppressed Ref-1-induced endothelial NO synthase (eNOS) phosphorylation and resulted in a corresponding inhibition of unstimulated- and bradykinin-stimulated NO production. These results suggest that Ref-1 stimulates direct phosphorylation of AKT for eNOS enzyme activity in murine endothelial cells.

• Korean Journal of Pharmacognosy
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• v.52 no.2
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• pp.92-98
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• 2021

Gryllus bimaculatus extract (GbE) have reported that anti-inflammatory activity by suppression of pro-inflammatory cytokines. However, the effects of fermented Gryllus bimaculatus extract (FGbE) have not yet been investigated. In this study, we evaluated the anti-inflammatory and anti-wrinkle effect of the fermented Gryllus bimaculatus extracts using Bacillus subtilis (JB PMB-18) in RAW264.7 cells. Both GbE and FGbE exerted no cytotoxic effects until 1000 ㎍/mL concentration. FGbE decreased NO production and decreased iNOS and COX-2 mRNA levels in a concentration-dependent manner. In addition, the protein production of inflammatory cytokines TNF-α, IL-1β and IL-6 was effectively reduced compared to the GbE. Inhibitory activities of elastase and collagenase associated with skin wrinkle improvement were measured to be 45% and 69%, respectively, at a concentration of 500 ㎍/mL in FGbE. From these results, FGbE can be used as a health functional food and skin functional cosmetic materials for preventing inflammatory diseases because it has excellent anti-inflammatory and anti-wrinkle effects.

• Journal of Life Science
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• v.26 no.3
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• pp.338-345
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• 2016

This study investigated the antioxidant and anti-inflammatory activity of ethanol extract from the flowers of Weigela subsessilis (WS-E) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The total polyphenol and flavonoid content was 719.19±0.04 μg tannic acid equivalents/ml and 644.87±0.02 μg quercetin equivalents/ml, respectively. The antioxidant activities of WS-E were measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging activity. The antioxidant activities of WS-E increased markedly, in a dose-dependent manner. To screen for anti-inflammatory agents, the inhibitory effects of WS-E on the production of proinflammatory cytokines in the LPS-stimulated RAW 264.7 macrophages was examined. WS-E had no effect on cell viability at a concentration of 100 μg/ml. Nitric oxide (NO) and interleukin (IL)-6 production were inhibited in a dose-dependent manner (p<0.05). WS-E had no effect on the production of tumor necrosis factor (TNF)-α at a concentration of 0.16–20 μg/ml but induced TNF-α at a concentration of 100 μg/ml. Inducible nitric oxide synthase (iNOS) expression was also inhibited at lower concentrations (p<0.05). In addition, WS-E reduced the activation of nuclear factor (NF)-κB by inhibition of inhibitoy (I) κB phosphorylation in RAW 264.7 macrophages upon stimulation with LPS (100 ng/ml) for 24 h but not that of mitogen-activated protein kinase (MAPK). These results suggest that WS-E may be a useful antioxidant and anti-inflammatory agent in functional cosmetics.

• Microbiology and Biotechnology Letters
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• v.45 no.1
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• pp.19-26
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• 2017

Effects of resveratrol glucosylation on the immunomodulation properties of resveratrol and on the viability of macrophage cells have been studied by using murine macrophage RAW 264.7 cells. Nitric oxide (NO) and interleukin 6 (IL-6) expression in macrophages in vitro were studied after treatment with different concentrations of (E)-resveratrol, (E)-resveratrol 3-O-${\beta}$-${\small{D}}$-glucoside (R-3-G), or (E)-resveratrol 4'-O-${\beta}$-${\small{D}}$-glucoside (R-4'-G). In vitro viability of RAW 264.7 cells after treatment with the aforementioned three compounds was also studied. As demonstrated by macrophage cell viability assays, two different resveratrol monoglucosides, R-3-G and R-4'-G, exhibited 50-80% reduced cytotoxicity in comparison to (E)-resveratrol in A549 and HepG2 cells. Compared to the resveratrol aglycon, both glucosylated resveratrol derivatives positively modulated NO and IL-6 production in macrophages positively via transcriptionally up-regulating IL-6 and iNOS expression. Conjugation of a glucose moiety on resveratrol was found to enhance the immunomodulating activity of resveratrol and the viability of RAW 264.7 cells.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.381-385
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• 2019

We attempted to examine anti-inflammatory and anti-oxidant effects of 4'-O-${\beta}$-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin $E_2$ ($PGE_2$) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). GOMV also scavenged free radicals in vitro, increased NF-E2-related factor 2 (NRF2), and activated antioxidant response element (ARE), thereby resulting in the induction of phase II cytoprotective enzymes in human keratinocyte HaCaT cells. Finally, GOMV significantly protected HaCaT cells against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative intracellular damages. Together, our results illustrate that GOMV possesses anti-inflammatory and anti-oxidant activity.