• Biomolecules & Therapeutics
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• 제24권5호
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• pp.543-551
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• 2016

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

• 한국식품영양학회지
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• 제29권3호
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• pp.431-437
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• 2016

본 연구는 전통약재로 주로 사용되는 구절초에서 분리한 다당류(CZPS)가 선천 및 적응면역에서 중추적인 역할을 수행하는 대식세포의 활성화에 미치는 영향에 관하여 관찰하였다. 구절초에서 분리한 다당류를 마우스 유래 대식세포주인 RAW 264.7 cell에 처리하였을 때, iNOS의 발현을 조절하여 NO의 생성이 증가되었으며, 또한 면역활성 물질인 TNF-${\alpha}$, IL-$1{\beta}$ 및 IL-6 등의 cytokine의 분비능이 증가되었으며, 이러한 면역활성 매개자인 NO 및 cytokine의 증가의 원인에 관한 정확한 면역세포내 신호전달에 관하여 알아본 결과, CZPS 처리는 MAPKs(ERK, p38)의 인산화를 촉진시키며, 이로 인한 전사인자인 NF-${\kappa}B$의 인산화를 증가시켜, 대식세포의 활성화를 유도시키는 것으로 관찰되었다.

• 생약학회지
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• 제37권2호통권145호
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• pp.110-115
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• 2006

Melittia inouei (Yuri Nabang) larvae are used as a crude drug in East Asia for treating stomach cancer and inflammation, and currently reared as a pharmaceutical insect in Jejudo, Korea. This study evaluated the immuno-modulating activity of these extracts, by determining the level of, cytokine production from mouse splenocytes stimulated with the extracts. The Melittia inouei larvae extracts did not induce the splenocyte proliferation. On the other hand, they stimulated the splenocytes to produce cytokines such as $TNF-{\alpha}$, whereas they did not stimulate IL10, IL12 or $IFN-{\gamma}$. The aqueous portion of its plant (Tri-chosanthis kirilowii) extract (sap) was found to be a potent inducer of NO production from the CPAE cells. However, it showed weak inhibitory effects on vascular endothelial growth factor (VEGF) production from splenocytes. These data suggests that a Melittia inouei larvae extract immune modulatory activity in cytokine prodcutions such as $TNF-{\alpha}$ and VEGF which might be related its anticancer effect.

• Asian-Australasian Journal of Animal Sciences
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• 제27권5호
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• pp.749-756
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• 2014

The present study was carried out to investigate the effects of dietary antioxidants on pro-inflammatory cytokines, heat shock protein (HSP) and antioxidant status in broiler chicks under summer conditions. A total of 162, 3-d-old broiler chicks were randomly assigned to a basal diet (CON) and the basal diet supplemented with vitamin C (200 mg/kg diet, VCD) or vitamin E (100 mg/kg, VED) until 35 day of age. All birds were exposed to summer diurnal heat stress at average daily fluctuations of temperature between $32^{\circ}C$ to $34^{\circ}C$ at day to $27^{\circ}C$ to $29^{\circ}C$ at night for the entire feeding periods. There was no significant difference in body weight, feed to gain ratio and the relative organ weight except the thymus in response to dietary vitamin C or E supplementation. However, the mRNA expression of interleukin (IL)-$1{\beta}$, IL-6, interferon (IFN)-${\gamma}$, Toll like receptor (TLR)-4 and HSP70 in the liver of birds fed diet containing vitamin C significantly (p<0.05) decreased compared with those in birds fed basal diet. Dietary vitamin E also showed a significant (p<0.05) decrease in the mRNA expression of IL-6 and HSP70 compared with a basal diet. Total antioxidant status (TAS) in serum of birds fed vitamin C supplemented diet was significantly (p<0.05) higher with than that in birds a basal diet. Lipid peroxidation in serum and liver resulted in a significant (p<0.05) decrease in response to dietary vitamin C or E supplementation. In conclusion, dietary supplementation with antioxidant vitamins, especially vitamin C resulted in a significant decrease in the mRNA expression of pro-inflammatory cytokines and HSP70, and higher antioxidant parameters than that of birds on the basal diet under summer conditions.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.92-92
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• 2019

Excessive or chronic inflammation contributes to the pathogenesis of many inflammatory diseases such as sepsis, rheumatoid arthritis, and ulcerative colitis. Hibiscus syriacus L. has been used as a medicinal plant in many Asian countries, even though its anti-inflammatory activity has been unclear. Therefore, we investigated the anti-inflammatory effect of anthocyanin fractions from the H. syriacus L. varieties Pulsae (PS) on the lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and cytokines in RAW264.7 macrophages. PS suppressed LPS-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) secretion concomitant with downregulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, PS inhibited the production of proinflammatory cytokines such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and IL-12 in LPS-stimulated RAW264.7 macrophages. Further study showed that PS significantly decreased LPS-induced nuclear translocation of the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) subunits, p65 and p50. Molecular docking data showed that many anthocyanins from PS fit into the hydrophobic pocket of MD2 and bound to Toll-like receptor 4 (TLR4), indicating that PS inhibits the TLR4-MD2-mediated inflammatory signaling pathway. Especially, apigenin-7-O-glucoside most powerfully bound to MD2 and TLR4 through LYS122, LYS122, and SER127 at a distance of $2.205{\AA}$, $3.098{\AA}$, and $2.844{\AA}$ and SER441 at a distance of $2.873{\AA}$ (docking score: -8.4) through hydrogen bonding, respectively. Additionally, PS inhibited LPS-induced TLR4 dimerization/expression on the cell surface, which consequently decreased MyD88 recruitment and IRAK4 phosphorylation. PS completely blocked LPS-mediated mortality in zebrafish larvae by diminishing the recruitment of neutrophil and macrophages accompanied by low levels of proinflammatory cytokines. Taken together, our results indicate that PS attenuates LPS-mediated inflammation in both in vitro and in vivo by blocking the TLR4/MD2-MyD88/IRAK4-$NF-{\kappa}B$ axis. Therefore, PS might be used as a novel modulatory candidate for effective treatment of LPS-mediated inflammatory diseases.

• 생명과학회지
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• 제24권1호
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• pp.61-66
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• 2014

본 연구는 면역억제 마우스에서 양강 에탄올 추출물이 면역증강에 미치는 영향을 평가해보았다. 마우스에 cyclophosphamide를 2회 복강 주사한 후 양강 추출물을 30, 100, 300 mg/kg 용량으로 4주간 경구투여 한 후, 체중 및 면역장기 무게, 비장세포수, 혈청 사이토카인 농도 및 혈청 면역글로불린의 농도를 측정하였다. 실험 결과 체중과 비장세포수는 양강 추출물 투여 시 대조군과 비교하여 유의한 차이를 보이지 않았다. 혈청의 IL-2, TGF-${\beta}$ 및 IFN-${\gamma}$ 농도는 AO 100군에서 대조군에 비해 유의적인 증가를 보였고(p<0.05) IL-4 농도는 실험군에서 유의한 차이를 보이지 않았다. 혈청 내 IgM의 농도는 대조군에 비해 양강 추출물 투여군 모두에서 유의적으로 증가하였고 (p<0.05), IgA의 농도는 양강 추출물 투여군에서 증가하는 경향을 보였는데 특히 AO100군에서 유의성 있게 증가하였다(p<0.05). 본 연구 결과는 양강 에탄올 추출물은 혈청 내 사이토카인 농도와 면역글로불린 농도를 증가시켜 면역력 증강에 기여할 것으로 보이며 특히 100 mg/kg을 투여하였을 때 효과가 가장 큰 것으로 나타났다.

• 약학회지
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• 제57권6호
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• pp.394-399
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• 2013

In this study we demonstrated whether the extract of Polygonum aviculare L. (PAE) can be applied to the immune-stimulating responses in macrophages (Raw 264.7 cells). Cell viability was determined by WST-8 assay, and all four doses of PAE (5, 10, 20, and 40 ${\mu}g/ml$) had no significant cytotoxicity during the entire experimental period. PAE increased the production of inducible nitric oxide synthase (iNOS) and nitric oxide (NO), and mRNA expressions and protein levels of pro-inflammatory cytokines(tumor necrotic factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6) in the same cells. These immune-stimulating activities of PAE were found to be caused by the stimulation of $NF{\kappa}B$ signal and phosphorylation of MAP kinases (p38, ERK and JNK).

• 한국미생물·생명공학회지
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• 제48권3호
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• pp.366-372
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• 2020

Since, side effects of antibiotics are frequently emphasized these days, their use is gradually diminishing, and alternative drugs are being developed. We have sought to reintroduce them as raw materials for human health as conventional 'weapons' that have been retired after their historical duties. In this study, we investigated the anti-inflammatory effects of lincomycin (LIN), on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our findings show that LIN potently inhibited production of LPS-induced proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E₂ (PGE₂), without cytotoxicity. Consistent with these findings, LIN strongly decreased protein expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, LIN reduced pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. To further elucidate the mechanisms of these inhibitory effects of LIN, we studied LPS-induced IκB-α degradation, and mitogen-activated protein kinase (MAPK) phosphorylation. LIN suppressed downregulation of inhibitory κB (IκB-α) degradation, and the phosphorylation of the c-Jun N-terminal kinase (JNK) pathway. Based on these results, we suggest that LIN may be considered a potential candidate as an anti-inflammatory cosmetic or a medicine for human health.

• Journal of Microbiology and Biotechnology
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• 제23권12호
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• pp.1691-1698
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• 2013

The anti-inflammatory effects of Sargassum micracanthum ethanol extract (SMEE) was investigated using LPS-induced inflammatory response in this study. As a result, there was no cytotoxicity in the macrophage proliferation treated with SMEE compared with the control. SMEE inhibited production of nitric oxide and cytokines (IL-6, TNF-${\alpha}$, and IL-$1{\beta}$) in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase and cyclooxygenase 2 were suppressed via inhibition of nuclear factor ${\kappa}B$ p65 expression by SMEE treatment. The formation of edema in the mouse ear was reduced at the highest dose tested compared with that in the control, and reduction of ear thickness was observed in histological analysis. Moreover, in an acute toxicity test, no mortalities occurred in mice administered 5,000 mg/kg body weight of SMEE over a 2-week observation period. These results suggest that SMEE may have significant effects on inflammatory mediators and be a potential anti-inflammatory therapeutic material.

• 대한본초학회지
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• 제21권4호
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• pp.93-101
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• 2006

Objectives : Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease(AD), Parkinson's disease(PD) and Huntington's disease(HD) in the inflammatory process. Uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$ and IL-6), NO, PEG2 and superoxide. In this study, the immunomodulatory effects of the herbal extract Panax notoginseng on cultured BV2 microglial cells and primary microglia were investigated to address potential therapeutic or toxic effects. Notoginseng radix extracts extracted from the root of the plant using Methanol. Methods : Cells were stimulated with LPS and treated with notoginseng at different concentrations. Results : Notoginseng significantly decreased LPS-induced production of $TNF-{\alpha}$ and IL-6 by the cultured microglial cells in a dose-dependent manner. The activation of iNOS mRNA and secretion of nitric oxide(NO) in microglial cells were inhibited in microglial cells in a dose-dependent manner by notoginseng. Conclusion : These results indicate that notoginseng inhibits LPS-induced activation of microglial cells and demonstrates notoginseng possess anti-inflammatory and immunosuppressive properties in vitro.