• Biomolecules & Therapeutics
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• 제5권2호
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• pp.202-210
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• 1997

Protective effect of DA-9601, an extract of Artemisia Herb, against ethanol-induced gastric mucosal injury was evaluated in rats. In the prophylactic study, DA-9601 exhibited total protection (99.4%) against absolute ethanol-induced gastropathy, And the protective effect of DA-9601 lasted up to 2 hours, which was longer than those of other contemporary mucoprotectants. In the treatment study, DA-9601 significantly facilitated the healing of 70% ethanol-induced mucosal damage, which was superior to cetraxate, a commonly used anti-ulcer drug. The mechanisms of mucoprotection of DA-9601 were also assessed. DA-9601 increased the release of prostaglandin E$_2$ from murine neutrophils in a dose-dependent manner in vitro. The cytoprotective effect of DA-9601 against ethanol-induced mucosal damage was significantly diminished by the concommitant injection of N$\omega$-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, i.v.), a non-specific nitric oxide (NO) synthase inhibitor, while it was not affected by preinjection of indomethacin (5 mg/kg, s.c.), a prostaglandins-depletor. And it was found that DA-9601 significantly enhanced adaptive cytoprotective action of 10% ethanol against absolute ethanol (56.9$\pm$6.5 vs 23.0$\pm$3.3 mm$^2$, p<0.05, mean$\pm$SEM), though its exact underlying mechanism remains to be clarified. The present fin[lings demonstrate that DA-9601 exerts gastroprotecticv actions for the stomach against ethanol through several different underlying mechanisms, in which prostanglandins and NO are involved. In conclusion, the results obtained suggest that DA-9601 can be useful both in prevention and treatment of ethanol-induced gastric damage.

• Journal of Periodontal and Implant Science
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• 제25권2호
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• pp.386-396
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• 1995

Interieukin 1${\beta}$ is a potent bone resorptive cytokine which mediates soft tissue destruction through the stimulatidn of prostaglandin production and the induction of collagenase. This constellation of activities suggests a role of IL-1${\beta}$ in the pathogenesis of periodontal disease. The purpose of this study was to evaluate the effects of herbal extracts on production and activity of IL-1${\beta}$. When LPS was added to cultured human blood monocytes, the effects of herbal extracts on the production of IL-1${\beta}$ was evaluate by thymocyte stimulation assay. When rHuIL-1${\beta}$ was added to cultured human gingival fibroblasts, the effects of herbal extracts on production of $PGE_2$ was evaluated by ELISA and when it was added to cultured mouse calvaria, the effects on bone resorption was estimated by .$^{45}Ca$-release bone resorption assay. The herbal extracts that had been used in this study were as follows; Asparagi Radix, Schzandrae Fractus, Zizyphi Fractus and Rhois Galla. The following results were obtained from this study. 1. All these extracts effectively inhibited the production of IL-1${\beta}$ on cultured human blood monocytes. 2. All these extracts effectively inibited the production of $PGE_2$ on cultured human gingival fibroblasts. 3. All these extracts did not effectively inhibit the bone resorption induced by rHulL-1${\beta}$ on cultured mouse calvaria.

• Animal cells and systems
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• 제3권4호
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• pp.385-391
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• 1999

Changes in the levels of prostaglandian F$_{2a}$ (PGF$_{2a}$) and E$_2$ (PGE$_2$) in culture medium during in vitro ovulation of Rana dybowskii follicles were examined. The ovulation was induced by frog pituitary homogenate (FPH) or TPA (12-O-tetradecanoylphorbol-13-acetate, a protein kinase activator) and the levels of PGs were measured by radioimmunoassay. When the ovarian follicles were cultured, only a few oocytes were ovulated by 12 h, but half of them were ovulated by 24 h in response to FPH, whereas around 30% of oocytes were ovulated by 12 h and maximum ovulation (around 50%) occurred by 24 h in response to TPA. Without any stimulation (control), no ovulation occurred. TPA elevated the level of PGF$_{2a}$ to high levels when compared to control (basal levels), but the increase by FPH was less evident. Likewise, the levels of PGE$_2$ increased markedly in response to TPA, but rather decreased by FPH treatment. Interestingly, PGF$_{2a}$ induced ovulation but PGE$_2$ suppressed FPH- or PGF$_{2a}$-induced oocyte ovulation. Basal levels of PGs Increased steadily during culture. When theca/epithelium (THEP) layer and granulosa cell-enclosed oocytes (GCEOs) were separated by microdissection and cultured independently, higher levels of both PGs were secreted by THEP than by GCEOS. Synthesis of PGs by follicle or follicular components was strongly suppressed by exogenous cAMP or indomethacin. These results suggest that: 1) PGF$_{2a}$ plays an important role in Rana ovulation, 2) protein kinase C is involved in PGs production, and 3) thecal epithelium layer is responsible for the PGs production in Rana.

• Journal of Periodontal and Implant Science
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• 제29권4호
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• pp.995-1005
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• 1999

Alveolar bone destruction is a character-istic of periodontal disease. Treponema denticola are found in significantly increased numbers in the sites affected with periodontal disease. In order to clarify the role of T. denticola in destruction of alveo-lar bone in periodontal disease, this study was undertaken to determine the effect of sonicated extract of T. denticola on osteo-clast differentiation in co-culture system of mouse bone marrow cells and calvaria cells. The ability of osteoclast formation was estimated by counting the number of tar-tartrate resistant acid phosphatase(TRAP) positive cells. Sonicated extract of this bacteria stimulated osteoclast formation in a dose dependent manner(p<0.05). Indomathacin, an inhibitor of prostaglandin synthesis, decreased osteoclast formation induced by sonicated extract of this bacte-bacteria(p<0.05). Extract-induced osteoclast formation was decreased, when sonicated extract of bacteria was heated(p<0.05). These findings suggest that T. denticola induces osteoclast differentiation, and protein component of this bacteria and $PGE_2$ may play an important role in this process.

• Nutrition Research and Practice
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• 제11권2호
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• pp.90-96
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• 2017

BACKGROUND/OBJECTIVES: Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS: Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and $30{\mu}M$ lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B ($NF-{\kappa}B$), inhibitor kappa B ($I{\kappa}B$), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were determined via enzyme-linked immunosorbent assays. RESULTS: In cells treated with lycopene and LPS, the mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of $PGE_2$ and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of $NF-{\kappa}B$ and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS: Lycopene restrains $NF-{\kappa}B$ and JNK activation, which causes inflammation, and suppresses the expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.

• Journal of Periodontal and Implant Science
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• 제33권1호
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• pp.79-89
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• 2003

치주질환은 세균감염에 의해 치조골이 파괴되는 염증성질환으로서 치아상실의 주된 원인이다. Treponema denticola는 성인성 치주염의 병소에서 자주 발견되는 세균으로서 부착능 및 단백분해효소생성능과 같은 독성 인자가 밝혀져 치주조직 파괴에 있어서 중요성이 강조되어 왔다. 골개조는 조골세포의 골형성및 파골세포에 의한 골흡수의 균형에 의하여 유지되며 치주염시 야기되는 치조골파괴는 조골세포 및 파골세포 기능의 불균형에 의하여 야기되는 것으로 설명되고 있다. 골세포에 대한 영향으로서 T. denticola는 파골세포의 형성을 촉진시키는 것으로 보고되었으나 조골세포에 대한 영향은 아직 밝혀져 있지 않다. 따라서 본 연구에서는 T. denticola가 골형성에 미치는 영향을 알아보고자 마우스의 두개골세포로부터 조골세포를 분리한 후 T. denticola분쇄액으로 처리하여 본 세균이 조골세포의 alkaline phosphatase(ALPase) 활성, 석회화결절 형성 및 Prostaglandin $E_2\;(PGE_2)$ 생성에 미치는 영향을 평가하였다. ALPase활성은 p-nitrophenylphosphate분해능, 석회화결절형성은 Von Kossa 염색법, 그리고 PGE2의 농도는 효소면역측정법으로 측정하였다. T. denticola분쇄액 (2.5 ug/ml)은 마우스 두개골세포의 ALPase활성을 억제하였으며 석회화결절의 형성을 감소시켰다. 또한 동일한 농도의 균분쇄액은 마우스 두개골세포의 $PGE_2$ 생산을 증가시켰다. 균분쇄액과 prostaglandin의 합성억제제인 indomethacin으로 세포를 동시에 처리한 경우 T .denticola분쇄액에 의한 $PGE_2$의 생산은 감소되었으나, ALPase의 활성억제에는 변화가 없었다. 균분쇄액을 열처리하여 마우스 두개골세포에 처리하였을 때에도 ALPase의 활성이 억제되는 것에는 변함이 없었다. 이러한 결과는 T. denticola의 구성성분 중 열에 안정한 물질이 prostaglandin과 무관한 경로를 통해 조골세포의 분화를 억제함을 시사하며 이와 같은 T. denticola에 의한 골형성억제가 치주염시 야기되는 치조골 파괴에 관여할 수 있을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.435-441
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• 1998

We examined effects of interleukin $1{\alpha}$ ($IL1{\alpha}$) and phorbol 12, 13 dibutyrate (PDB), an activator of protein kinase C, on mRNA for Prostaglandin H synthase (PGHS) and prostanoid production in cultured ovine meningeal fibroblasts. Immuno- and morphologically-identified fibroblasts were derived from cerebral cortex and white matter from fetal lambs (approximately 120 days gestation) and grown to confluence on glass coverslips in 12 well plates. Levels of prostaglandin $F_{2{\alpha}}$ and the stable hydrolysis product of prostacyclin (i.e., $6-keto-PGF_{1{\alpha}}$) were determined using enzyme immunoassay. Relative amounts of mRNA were determined by in situ hybridization using ovine cDNA for PGHS1. $IL1{\alpha}$ (10 ng/ml) increased mRNA levels over baseline by $62{\pm}19%$ (p＜0.05) at 60 min., $37{\pm}12%$ (NS) at 120 min., and $36{\pm}18%$ (NS) at 240 min (n=12). Levels of $6-keto-PGF_{1{\alpha}}$ were $148{\pm}18%$ pg/ml during baseline, $246{\pm}41%$ pg/ml at 60 min., $248{\pm}40%$ pg/ml at 120 min., and $259{\pm}62%$ pg/ml at 240 min (all p＜0.05) (n=12). $PGF_{2{\alpha}}$ was increased although it wasn't statistically significant. However, $IL1{\alpha}$ decreased $PGE_2$ level significantly (all p＜0.05). PDB $(10^{-6}M)$ increased mRNA levels over baseline by $25{\pm}6%$ after 30 min., $40{\pm}6%$ after 60 min., and $20{\pm}8%$ after 90 min. (n=9) (all p＜0.05). Levels of $6-keto-PGF_{1{\alpha}}$ were $200{\pm}43%$ pg/ml during baseline, $202{\pm}43%$ pg/ml after 30 min. (NS), $268{\pm}58%$ pg/ml after 60 min. (p＜0.05), and $296{\pm}60%$ pg/ml after 90 min. (p＜0.05) (n=9). Levels of $PGF_{2{\alpha}}$ were $178{\pm}26%$ pg/ml during baseline, $300{\pm}30%$ pg/ml after 30 min., $299{\pm}35%$ pg/ml after 60 min., and $355{\pm}32%$ pg/ml after 90 min (all p＜0.05) (n=6). Actinomycin-D (1 mg/ml) prevented increases in mRNA, $6-keto-PGF_{1{\alpha}}$, and $PGF_{2{\alpha}}$ at 60 min. for both $IL1{\alpha}$ and PDB. We conclude that cerebral fibroblasts are avid producers of prostanoids, and that enhanced production of PGHS is responsible for augmented $PGF_{2{\alpha}}$ and prostacyclin production in the presence of an activator of protein kinase C and for decreased $PGE_2$ and increased prostacyclin production in the presence of $IL1{\alpha}$.

• 대한치과교정학회지
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• 제26권1호
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• pp.83-94
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• 1996

Substance P는 교정력이 가해진 치아의 치주인대 중 인장력을 받는 부위에 많이 분포하는 neuropeptide중의 하나이며, 또한 여러 조직에서 neurogenic inflammation을 야기하는 neuropeptide중의 하나로도 알려져 있다. 그러나 중요한 세포외 단백기질인 교원질의 생성에 대한 Substance P의 효과는 잘 알려져 있지 않다. 따라서 이 연구의 목적은 배양치주인대 세포에서 교원질 생성에 대한 Substance P의 효과를 평가하는 것이었다. collagenase-digestion method로 교원질 생성을 평가하였고 mRNA 수준에서 작용효과를 평가하기 위하여 Northern blot hybridization을 시행하였다. 이 연구는 또한 교원질 생성에 대한 prostaglandin과 gelatinase 생성도 포함하였으며 변성된 교원질의 분해를 평가하기 위하여 zymography를 이용하였다. 비교원성 단백질, 교원성 단백질, 상대교원질에 대한 dose-dependent effect를 보면 Substance P는 비교원성 단백질 합성을 증가시켰으나 교원성 단백질 합성은 감소시킨다. 그리하여 총 단백합성에 대한 상대적인 교원질 생성을 나타내는 상대교원질은 $7\%$에서 $3.6\%$로 감소시켰다. 세포를 indomethacin과 동시에 처리할 때 substance P의 교원질 합성 억제효과는 나타나지 않았다. 이것은 Substance P의 교원질 합성 억제효과가 prostaglandin의 생성 때문이라는 것을 의미한다. Substance P의 교원질 합성 억제효과가 procollagen mRNA의 정상(steady-state)수준에 부합하는가를 평가하기 위하여 northern blot hybridization을 시행한 결과 Substance P는 ${\alpha}1(1)$ procollagen mRNA의 양적 변동을 일으키지 않았다. Substance P의 교원질 생성 억제효과는 전사이후의 어떤 단계에서 이루어지는 현상임을 나타낸다. 치주인대세포에서 gelatinase 생성에 대한 Substance P의 효과를 알아보기 위하여 zymography를 이용하였다. zymogram 을 보면 Substance P는 치주인대세포에서 gelatinase 생성에는 아무 효과도 나타내지 않음들 알 수 있다. Substance P의 교원질 생성 억제효과가 치주인대세포에 대해 선택적인가 아닌가를알아보기 위하여 MC3T3-E1세포를 이용하였는데 Substance P는 MC3T3-E1세포의 교원질 합성에는 영향을 미치지 않았다. 이상에서 Substance P는 인간의 치주인대세포에서 교원질 합성을 억제하였다. 이 효과는 procollagen mRNA와 gelatinase 생성의 정상(steady-state) 수준의 변화 때문이 아니라 prostaglandin 생성과 연관이 있음을 알았다.

• 대한본초학회지
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• 제23권2호
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• pp.51-58
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• 2008

Objectives : Trimellitic anhydride (TMA), a sensitizer that induces occupational asthma and atopic dermatitis, is widely used industrially to make epoxy and alkyd resins, plasticizers, high temperature polymer, and surfactants. The aim of this study was to investigative the effects of aqueous extracts of Lonicera japonica Flower(LJFAE) on TMA-induced contact hypersensitivity (CHS) in Balb/c mice. Methods : The dried flowers of L. japonica were extracted with distilled water at $100^{\circ}C$ for 7 h. The extract was freeze-dried following filteration through 0.45 ${\mu}m$ filter. Mice were orally administrated with or without LJFE of a different doses(25-100 mg/kg) for 28 days. In the challenge period, mice were externally applied at difference doses of LJFAE one time per day 30 min before TMA treatment. We examined the effects of LJFAE on the the serum levels of IgE and prostagladin E2 (PGE2), the Thl/Th2 cytokine production of spleen cells, ear swelling responses, and the leukocyte infiltration induced by TMA. Results : The orally and externally administration of LJFAE dose-dependently reduced the serum levels of IgE and PGE2 production as well as ear swelling responses and leukocyte infiltration in TMA-induced Balb/c mice. Furthermore, the levels of Thl (TNF-${\alpha}$, IFN-${\gammer}$, IL-2)/Th2 (IL-4, IL-5, IL-13) cytokine production from spleen cells stimulated with anti-CD3 and CD28 mAbs was markedly suppressed by the orally and externally treatment with LJFAE in a concentration dependent manner. Conclusions : These results suggest that LJFAE suppresses the inflammatory mediators and regulates the Thl/Th2 cytokines. Therefore, these properties may contribute to the strong anti-CHS response effect of LJFAE.

• Mycobiology
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• 제43권3호
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• pp.319-326
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• 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.