• Title/Summary/Keyword: iNOS synthesis

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Human placental extract suppresses lipopolysaccharide-induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells

  • Yang, Sang-Eun;Kim, Yong-Suk;Park, Dong-Suk
    • Journal of Acupuncture Research
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    • v.22 no.2
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    • pp.111-121
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    • 2005
  • Human placental extract (HPE), which is prepared from the placenta of healthy pregnant females, has been widely used in clinical field. HPE is known to possess anti-inflammatory, anti-viral, anti-oxidative, anti-mutagenic, and analgesic properties. In this study, the effect of HPE against lipopolysaccharide (LPS)-induced inflammation was investigated. From the present results, HPE was shown to suppress prostaglandin E2 synthesis (PGE2) and nitric oxide (NO) production by inhibition on the LPS-stimulated enhancement of the cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in mouse BV2 microglial cells. These results suggest that HPE may offer a valuable mean of therapy for the treatment of brain inflammatory diseases by attenuating LPS-induced PGE2 and NO production.

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Synthesis and Biological Evaluation of Militarin Derivatives (밀리타린 유도체의 합성 및 생리활성 평가)

  • Che, Haiyan;Yoon, Deok Hyo;Kim, Tae Woong;Sung, Gi-Ho;Park, Haeil
    • YAKHAK HOEJI
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    • v.56 no.6
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    • pp.372-376
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    • 2012
  • Militarin was isolated from Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom and reported to possess anticancer activities against several tumor cells. A number of militarin derivatives bearing different numbers of ethylene glycol unit were synthesized and evaluated for their biological activities related with anticancer and antiinflammatory effects. Among militarin derivatives tested, the compounds 2 and 5 exhibited anticancer and antiinflammatory activities.

Inducible nitric oxide synthase is involved in neuronal death induced by trimethyltin in the rat hippocampus (Trimethyltin에 의한 랫드 해마의 신경세포 사멸과 iNOS의 연관성)

  • Jang, Sukwon;Choi, Sungyoung;Park, Changnam;Ahn, Meejung;Shin, Taekyun;Kim, Seungjoon
    • Korean Journal of Veterinary Research
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    • v.51 no.3
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    • pp.185-191
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    • 2011
  • Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.

Anti-inflammatory Activities Verification of Ambrosia trifida L. extract in RAW 264.7 Cells (RAW 264.7 세포에서의 단풍잎돼지풀 추출물의 항염증 활성 검증)

  • Yoo, Dan-Hee;Lee, Jin-Young
    • Microbiology and Biotechnology Letters
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    • v.48 no.1
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    • pp.79-89
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    • 2020
  • This study was performed to evaluate the anti-inflammatory activities of 70% ethanol extract from Ambrosia trifida L. (AT). The electron donating ability and ABTS+ radical scavenging ability of extract from AT was shown to be 84.1% and 92.5% at 1,000 ㎍/ml concentration. The astringent effect of extract from AT was shown to be 94.7% at 1,000 ㎍/ml. The anti- inflammatory activities of extract of AT were investigated using RAW 264.7 cells induced by lipopolysaccharide (LPS). The cell toxicity effect of AT extract on RAW 264.7 performed MTT assay. As a result of the measured cell toxicity effect, 90% or more was shown with cell viability at a 500 ㎍/ml concentration. In nitric oxide synthesis inhibition effect, it was shown that extract from AT concentration dependent inhibited nitric oxide production. The protein expression inhibitory effect of AT extract was measured by western blot at 25, 50, and 100 ㎍/ml concentration and the β-actin used as a positive control. Consequently, the inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 protein expression inhibitory effect was decreased by 8.6%, 25.1% at 100 ㎍/ml concentration. The phosphorylation of extracellular signal-regulated kinase 1/2, p38, c-Jun NH2-terminal kinase and Iκ-Bα protein expression inhibitory effect was a decreased dependent concentration. The mRNA expression inhibitory effect was measured by reverse transcription - polymerase chain reaction at 25, 50, and 100 ㎍/ml concentration and the glyceraldehyde-3-phosphate dehydrogenase used as a positive control. Consequently, the iNOS, COX-2, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α mRNA expression inhibition effect was a decreased dependent concentration in an LPS-activated macrophage. In conclusion, AT extract may have some effects on inflammatory factors as potential anti-inflammatory agents and natural substance for cosmetics.

Anti-inflammatory effects of a mixture of coffee and sword bean extracts (커피와 작두콩 추출물의 혼합에 따른 항염증 효과)

  • Bae, Hun Cheon;Park, Jung Up;Moon, Jae-Hak
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.237-243
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    • 2020
  • Coffee is one of the most widely consumed beverages in the world, and sword bean (Canavalia gladiata, SB) reportedly possesses various biological activities. Therefore, in this study, to reduce caffeine intake and improve coffee function, SB was selected as a supplementary material for blending coffee. The antioxidant and anti-inflammatory activities of coffee with the SB extract at concentrations of 0.1-0.5% (v/v) were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and RAW 264.7 cells, respectively. The DPPH radical-scavenging activity of SB-treated coffee depended on the concentration of the SB extract. In the cell culture experiment, cytotoxicity was not observed at any SB concentration. In addition, the inducible nitric oxide synthesis protein expression as well as the increases in nitric oxide and interleukin-6 expression were effectively inhibited by SB addition to the coffee. These results indicate that SB might be useful as a supplementary ingredient to enhance the caffeinated drink functions.

Effects of Dokhwalgisaengtang-gami Water Extract on Osteoclast Differentiation and Osteoblast Function in RANKL-induced RAW 264.7 Cell (독활기생탕가미방(獨活寄生湯加味方)이 파골세포 분화 억제와 조골세포 활성에 미치는 영향)

  • Je, Yun-Mo;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.2
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    • pp.1-16
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    • 2013
  • Objectives: This study was performed to evaluate the effect of Dokhwalgisaengtang-gami water extract(DGG) on osteoporosis. Methods: The osteoclastogenesis and gene expression were determined in RANKL-stimulated RAW 264.7 cell. And osteoblastogenesis was also determined in rat calvarial cell. Results: The results were summarized as followes. 1. DGG decreased the number of TRAP positive cell in RANKL-stimulated RAW 264.7 cell. 2. DGG inhibited TRAP activity in RANKL-stimulated RAW 264.7 cell. 3. DGG decreased the expression of NAFTc1, MITF in RANKL-stimulated RAW 264.7 cell. 4. DGG increased the expression of iNOS, COX-2, IL-6 in RANKL-stimulated RAW 264.7 cell. 5. DGG decreased the expression of cathepsin K, MMP-9, TRAP in RANKL-stimulated RAW 264.7 cell. 6. DGG increased cell proliferation of rat calvarial cell. 7. DGG increased ALP activity in rat calvarial cell 8. DGG increased bone matrix protein, collagen synthesis and nodule formation in rat calvarial cell. Conclusions: It is concluded that DGG might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression. And DGG might increase the bone formation resulted from increase of osteoblast function.

A77 1726 Inhibit NO-induced Apoptosis via PI-3K/AKT Signaling Pathway in Rabbit Articular Chondrocyte

  • Choi, In-Kyou;Kim, Song-Ja
    • Biomedical Science Letters
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    • v.15 no.1
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    • pp.61-66
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    • 2009
  • Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis (RA). Leflunomide known as a regulator of iNOS synthesis which largely decreases NO production in diverse cell type. However, the effect of leflunomide on chondrocyte is still poorly understood. In our previous studies, we have shown that direct production of Nitric oxide (NO) by treating chondrocytes with NO donor, sodium nitroprusside (SNP), causes apoptosis via p38 mitogen-activated protein kinase in association with elevation of p53 protein level, caspase-3 activation. In this study, we characterized the molecular mechanism by which A77 1726 inhibit apoptosis. We found that A77 1726 inhibit NO-induced apoptosis as determined by MTT (Thiazolyl Blue Tetrazolium Bromide) assay and DNA fragmentation. The inhibition of apoptosis by A77 1726 was accompanied by increased PI-3 kinase and AKT activities. So, inhibition of phosphatidylinositol (PI)-3kinase with LY294002 rescued apoptosis. Triciribine, the specific inhibitor of AKT, also abolished anti-apoptotic effect. Our results indicate that A77 1726, the active metabolite of leflunomide, mediates NO-induced apoptosis in chondrocytes by modulating up-regulation of PI-3 kinase and AKT.

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Morus Nigra Extract Attenuates Cognition Impairment and GABAergic Interneuron Degeneration in Aged Rat Brain

  • Lee, Joo Hee;Kim, Yoonju;Song, Min Kyung;Kim, Youn-Jung
    • Journal of Korean Biological Nursing Science
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    • v.24 no.2
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    • pp.77-85
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    • 2022
  • Purpose: Aging process comes with cognitive impairment due to decreased neuronal cell number, activity, and neuronal circuit. Alteration of inhibitory neurons contributes to cognitive impairment in normal aging and is responsible for disrupting the excitation/inhibition balance by reducing the synthesis of gamma-aminobutyric acid (GABA). Morus nigra (Mulberry) is a natural physiologically active substance that has been proven to have anti-oxidant, anti-diabetic, and anti-inflammatory effects through many studies. This study aimed to evaluate the effects of the mulberry extract (ME) on cognitive function through anti-oxidant enzyme and GABAergic neuronal activity in aged rat brain. Methods: Sprague Dawley rats were randomly assigned as the young group (8 weeks, n= 8), aging group (67 weeks, n= 8), and aging+ mulberry extract group (67 weeks, n= 8). The aging+ mulberry extract group was orally administered 500 mg/kg/d mulberry extract for 6 weeks. Results: The aging+ mulberry extract group improved spatial and short-term memory. The antioxidant potential of ME increased the expression of superoxide dismutase-1 (SOD-1) and decreased inducible nitric oxide synthase (iNOS). Also, the aging+ mulberry extract group significantly increased the expression of GABAergic interneuron in hippocampus cornu ammonis1 (CA1) compared to the aging group. Conclusion: The number of GABAergic inhibitory interneurons was deceased and memory functions in the aging process, but those symptoms were improved and restored by mulberry extract administration.

Artemisolide from Artemisia asiatica: Nuclear $Factor-{\kappa}B\;(NF-{\kappa}B)$ Inhibitor Suppressing Prostaglandin $E_2$ and Nitric Oxide Production in Macrophages

  • Reddy, Alavala Matta;Lee, Jun-Young;Seo, Jee-Hee;Kim, Byung-Hak;Chung, Eun-Yong;Ryu, Shi-Yong;Kim, Young-Sup;Lee, Chong-Kil;Min, Kyung-Rak;Kim, Young-Soo
    • Archives of Pharmacal Research
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    • v.29 no.7
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    • pp.591-597
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    • 2006
  • Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as an oriental medicine for the treatment of inflammatory and ulcerogenic diseases. In the present study, artemisolide was isolated as a nuclear factor $(NF)-{\kappa}B$ inhibitor from A. asiatica by activity-guided fractionation. Artemisolide inhibited $NF-{\kappa}B$ transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an $IC_{50}$ value of $5.8\;{\mu}M$. The compound was also effective in blocking $NF-{\kappa}B$ transcriptional activities elicited by the expression vector encoding the $NF-{\kappa}B$ p65 or p50 subunits bypassing the inhibitory kB degradation signaling $NF-{\kappa}B$ activation. The macrophages markedly increased their $PGE_2$ and NO production upon exposure to LPS alone. Artemisolide inhibited LPS-induced $PGE_2$ and NO production with $IC_{50}$ values of $8.7\;{\mu}M$ and $6.4\;{\mu}M$, respectively, but also suppressed LPS-induced synthesis of cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together, artemisolide is a $NF-{\kappa}B$ inhibitor that attenuates LPS-induced production of $PGE_2$ or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW 264.7. Therefore, artemisolide could represent and provide the anti-inflammatory principle associated with the traditional medicine, A. asiatica.

Anti-Arthritic Effect of Sogyunghwalhyel-tang-gamibang (소경활혈탕가미방(疎經活血湯加味方)의 관절염에 미치는 효과)

  • Jo, Joo-hyun;Im, Ji-sung;Kim, Jong-gyu;Park, Jung-hyun;Choi, Hag-soon;Hwang, Geu-won;Song, Yung-sun
    • Journal of Korean Medicine Rehabilitation
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    • v.31 no.1
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    • pp.33-46
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    • 2021
  • Objectives The aim of this study is to evaluate anti-inflammatory and anti-arthritic effects of Sogyunghwalhyel-tang-gamibang (SGHHTGB) in cell and animal models and also to suggest one of putative mechanisms underlying its anti-arthritic effects. Methods Enzyme-linked immunosorbent assay was applied to measure the concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in culture medium and blood serum and nitric oxide (NO) was assayed by Griess reagent. The expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by Western blot method. Results In a cell model using RAW264.7 macrophages stimulated with the endotoxin lipopolysaccharide (LPS), the drug, at its non-cytotoxic concentrations, inhibited the production of the pro-inflammatory cytokine TNF-α, IL-1β and IL-6. In addition, it suppressed the expression of the inflammatory enzyme iNOS and COX-2, and reduced the synthesis of the enzyme product NO (as stable nitrite) and PGE2 in activated macrophages. Meanwhile, in an animal model using rheumatic arthritis (RA) mice induced with injection of type II collagen antibody (CAb) and LPS, the drug improved clinical symptom of arthritis and reduced paw thickness and inflammatory cell infiltration. In blood of RA mice, the drug reduced serum levels of TNF-α, IL-1β, IL-6, nitrite, and PGE2, all inflammatory mediators produced by activated macrophages. Conclusions SGHHTGB may ameliorate CAb and LPS-induced RA in mice, presumably by inactivating macrophages that are capable of initiating joint inflammation by producing pro-inflammatory cytokines and expressing inflammatory enzymes.