• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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• pp.325-331
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• 2000

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ plays important roles in inflammatory responses. Some of tetrahydroisoquinoline (THI) compounds exhibited to inhibit iNOS expression in animal studies and RAW 264.7 cells, but the action of THI on inflammatory reaction was not fully investigated. In the present study, we examined a limited series of THIs (higenamine, YS-51 and THI-52) on the $TNF-{\alpha}$ mRNA expression in mouse peritoneal macrophages by Northern analysis. When thioglycollate-stimulated peritoneal macrophages were incubated with LPS (100 ng/ml), expression of $TNF-{\alpha}$ mRNA was evident and reached its maximum at 2.5 h, which was reduced concentration-dependently by treatment with THIs. When the $TNF-{\alpha}$ activity of macrophage-conditioned media was measured using a TNF-sensitive L929 fibroblast cell line, CCL 1, all THIs increased the cell viability in a concentration dependent manner. The concentrations of THIs used are not cytotoxic by itself when analysed by MTT. Furthermore, nitrite/nitrate level was significantly reduced by the presence of THIs in cells treated with $LPS+interferon-{\gamma}\;(IFN-{\gamma}).$ It is concluded, thus, that these results strongly indicated that THIs can suppress the $TNF-{\alpha}$ expression and reduce NO, which may be useful for the inflammatory disorders.

• Journal of Ginseng Research
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• 제43권3호
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• pp.394-401
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• 2019

Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.

• 약학회지
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• 제42권6호
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• pp.558-566
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• 1998

Two isoforms of cyclooxygenase (COX) have been identified - COX-1, which is constitlitively expressed in most tissues, and the inducible form, COX-2, of which expression is induced by inflammatory signals and mitogens. It has been considered that the beneficial effects of NSAIDs are due to the inhibition of COX-2 activity and the side effects are from the inhibition of COX-1 activity. Therefore, it is essential to develop selective COX-2 inhibitor for developing new GI-tolerable NSAIDS. To discover new leads for developing selective COX-2 inhibitors, three-hundred extracts of natural products were primarily screened with the system of prostaglandin accumulation in LPS-stimulated mouse peritoneal macrophages. To identify whether these inhibitory activities of crude extracts on the accumulation of Prostaglandins were derived from direct action against COX-2, the effects of selected extracts on exogenous arachidonic acid-derived production of prostaglandins by LPS-stimulated macrophages were determined. Among them, 5 methanol extracts of natural products, such as Zingiberis Rhizoma, Alpinae Officinarum Rhizoma, Caryophilli Flos, Scutellariae Radix, Dalbergia ordorifera. inhibited more than 70% of the prostaglandin production in LPS-stimulated mouse peritoneal macrophages at a con-centration of 1${\mu}$g/ml.

• 한방안이비인후피부과학회지
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• 제28권4호
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• pp.92-110
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• 2015

Objectives : The water extract of Bowon-tang composited with thePanax, AstragalusandGlycyrrhiza Radixhas been traditionally used for treatment of a sickly child and smallpox in oriental medicine. However, little is known about the regulatory effects of Bowon-tang on the production, expression and activity of immune mediators [nitric oxide, prostaglandin E2, inducible nitric oxide synthetase, cyclooxygenase-2], the macrophage activation factor production, the proliferation, subset expression, the killing activity, and the capping in immune cells.Methods : In this study, we investigated the effects of water extracts from Bowon-tang,Panax, AstragalusorGRin mouse immune cells or human Jurkat T cells. Each extract (25-200 ㎍/㎖)perse had no cytotoxic effect in unstimulated macrophages, but concentration-dependently regulated NO and PGE₂production, iNOS expression, and COX-2 activity in mouse peritoneal macrophages with MAF stimulation. These regulatory effects were synergistically increased by their combination (Bowon-tang).Results : The extract of Bowon-tang concentration-dependently regulated T cell proliferation, CD4⁺and CD8⁺expression, and NK killing activity in mouse splenocytes and capping in Jurkat T cells.Conclusions : These results suggest that the water extract of Bowon-tang composited with thePanax, AstragalusandGRmay be useful for therapeutic drugs against a sickly constitution and immune diseases, probably by regulating the production of immune mediators.

• 한국식품영양학회지
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• 제24권1호
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• pp.65-70
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• 2011

This study was performed to investigate the in vitro effect of a corn water extract on immune function. Splenocyte proliferation was determined by the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl terazolium bromide) assay after preparing asingle cell suspension. Production of macrophage-secreted interleukin(IL)-$1{\beta}$, IL-6, and interferon(IFN)-${\gamma}$, was detected by ELISA using a cytokine assay kit. After a 48-hr incubation with mitogens(ConA or lipopolysaccharide), mice splenocyte proliferation increased with the addition of a corn water extract supplement at 10, 50, 100, 250, 500, or $1,000\;{\mu}g/m\ell$. Production of IL-$1{\beta}$, IL-6, and IFN-${\gamma}$ increased in treatments supplemented with the corn water extract. In an in vitro study, splenocyte proliferation increased when $50\sim1,000\;{\mu}\ell/m\ell$ corn water extract was added. In an ex vivo experiment, the highest production of cytokines by activated peritoneal macrophages was observed in mice orally administered 500 mg/kg body weight/day.

• 한국식품영양과학회지
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• 제26권1호
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• pp.148-153
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• 1997

본 연구는 전보의 영지버섯으로부터 분리 배양한 균 사체를 알카리추출하여 얻은 다당체의 일반성분과 당분석 및 항암작용에 관한 연구에 이어, 이들과 ATCC의 마우스 유래 탐식 세포주 TIB 71 및 BALB/c 마우스의 복강내 대식세포를 이용하여 영지버섯 다당체가 면역계 전체의 기능을 조정하는 대식세포의 면역기능에 미치는 영향을 연구하였다. 그 결과를 요약하면 다음과 같다 1. 대식세포의 환성에 영향을 미치는 영지 버섯 다당체의 효과를 알아보기 위하여 세포의 유사분 열능을 측정한 결과, 다당체의 처리 농도가 0.5mg 실험군에서부터 유의한 증가를 나타내었다(p<0.001). 2. 영지버섯 다당체가 대식 세포 활성에 미치는 효과를 알아보기 위해 대식세포의 표면에 존재하는 IL-2 수용체를 anti-mouse IL-2-FITC 단크론항체를 이용하여 측정한 결과는 PSG 0.05mg 실험군을 제외한 실험군 모두에서 대조군 37.6% 보다 현저한 발현증가(p<0.001)를 보였으며 PSG 0.1mg 실험군까지는 수용체가 증가 하나 그 이상 처리군 사이에서는 상호간 유의한 차이는 없었다. 3. 영지버섯 다당체는 대식 세포에서 유래하는 세포간물질 즉 IL-1, IL-6 및 TNF의 생성에 유의성 있는 관여는 하지 않는 것으로 생각되나 부분적으로 영지버섯 다당체와 BCG및 IFN-${\gamma}$를 모두 함께 병용 투여함으로써 각각 영지버섯 다당체와 BCG또는 영지버섯 다당체와 IFN-r을 투여하는 경우에 비하여 IL-1의 분비증가를 보였으며 TNF의 분비 역시 현저한 증가를 보여 영지버섯 다당체가 초기 감염시 숙주의 1차 방어기능에 관여함을 알 수 있었다.

• 동의생리병리학회지
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• 제22권6호
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• pp.1549-1556
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• 2008

The objective of this study were to evaluate the antioxidant activity and the anti-inflammatory effects of Angelica tenuissima (AT) which has been used widely as a traditional medicine. The antioxidant activities of AT was tested by DPPH radical scavenging, superoxide anion scavenging and nitric oxide scavenging. AT showed strong antioxidant activity in all experiment. In macrophages nitric oxide (NO) is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions and high concentratin of NO is produced by inducible nitric oxide synthase (iNOS). In this study we have examined the inhibition effects of NO by 85% methanol extracts of AT in mouse (C57BL/6) peritoneal macrophage. AT (100, 1000 ${\mu}g/m{\ell}$) suppressed nitric oxide production and iNOS expression without any notable cytotoxicity and it also inhibited the expression of inflammatoryenzymes like cyclooxygenase-2 (COX-2). These data suggest that 85% methanol extracts of AT may possibly be used as antioxidant and anti-inflammatory agent.

• 한국식품영양학회지
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• 제19권2호
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• pp.176-182
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• 2006

Sorghum bicolor L. Moench(Sorghum, Su-Su) is a major cereal food crop used in many parts of the world. It is used as a human food resource and folk medicines in Asia and Africa. The stem of sorghum has been used as a digestive aid and an anti-diarrheal agent. Sorghum hybrids contain high levels of diverse phenolic compounds that may provide health benefits. High levels of polyflavanols, anthocyanins, phenolic acids, and other antioxidant compounds have been reported in sorghums, which have also been shown to possess various biological activities such as anti-mutagenic, anti-carcinogenic, and HMG-CoA reductase inhibitory activities. In an in vitro experiment, we examined mice splenocyte proliferation and production of three types of cytokine($IL-1{\beta},\;IL-6,\;TNF-{\alpha}$) by peritoneal macrophages cultured with ethanol and water extracts of Sorghum bicolor L. Moench. A single cell suspension of splenocytes was prepared and the cell proliferation of the splenocytes was examined by MTT assay. The splenocyte proliferation was increased when water extracts of Sorghum bicolor L. Moench were used as supplements in all concentrations investigated. The production of cytokine($IL-1{\beta},\;IL-6,\;TNF-{\alpha}$) by activated peritoneal macrophage was detected by ELISA using the cytokine kit. $IL-1{\beta},\;IL-6,\;and\;TNF-{\alpha}$ production by activated macrophages were increased by supplementation with Sorghum bicolor L. Moench water extracts. This study suggests that supplementation of with Sorghum bicolor L. Moench water extracts may enhance immune function by regulating the splenocyte proliferation and enhancing the cytokine production by activated macrophages in vitro.

• Natural Product Sciences
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• 제20권2호
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• pp.113-118
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• 2014

Ribes fasciculatum which belongs to Saxifragaceae has been widely used as a traditional medicine for the treatment of symptoms associated with lacquer poison. However, pharmacological studies on the R. fasciculatum are extremely limited until now. Thus, in this study, we evaluated the possible anti-inflammatory effects of ethyl acetate fraction of R. fasciculatum (ERF) using IFN-${\gamma}$/LPS-stimulated peritoneal macrophage model. We investigated the change in nitrite level in the absence or presence of ERF after LPS stimulation, and we found that ERF effectively attenuates the NO production in a dose dependent manner without notable toxicity. To determine the mechanism of the inhibitory action of ERF on NO production, we performed iNOS enzyme activity assay and Western blotting. Here we showed that both of iNOS enzyme activities and iNOS expressions were significantly down-regulated by ERF, indicating that these dual activities of ERF are responsible for ERF-mediated NO suppression. In addition, ERF inhibitied the expression of cyclooxygenase-2 (COX-2), an another key enzyme in inflammation through suppression of NF-${\kappa}B$ activation. We also tested anti-inflammatory properties of ERF not only in vitro, but in vivo using trypsin-induced paw edema model in mice. Our results revealed that the increased paw volume in response to trypsin injection was recovered by ERF supplement dose dependently.

• 생약학회지
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• 제39권2호
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• pp.104-109
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• 2008

We previously reported that anti-inflammatory properties of poncirin, isolated from fruit of Poncirus trifoliata, might be the result from the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis $factor-{\acute{a}}$ ($TNF-{\alpha}$) and interlukin-6 (IL-6) expression via the down-regulation of $NF{-\kappa}B$ binding activity. In this study, we investigated whether poncirin has an inhibitory effect on the production of pro-inflammatory mediators ex vivo and whether poncirin could relieve the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice model of inflammatory bowel disease. Poncirin significantly inhibited the productions of NO, IL-6 and $TNF-{\alpha}$ in lipopolysaccharide (LPS)-induced mouse peritoneal macrophage. In addition, poncirin-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of poncirin-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). In addition, suppression of plasma NO and IL-6 productions of poncirin-treated mice was also observed in DSS-induced colitis. These results suggest that poncirin has potentially useful anti-inflammatory effects mediated by suppression of inflammatory mediator productions.