• Journal of Acupuncture Research
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• 제36권4호
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• pp.220-229
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• 2019

Background: The therapeutic potential of Bee Venom Pharmacopuncture (BVP) on acute ischemic cerebral infraction was determined in mice in vivo and in vitro. Methods: Analysis of acute ischemic cerebral infraction was performed using 7 week old male ICR mice (n = 20) and microglial BV-2 cells. Bee venom ($5{\mu}g/kg$) was injected into the caudal vein of middle cerebral artery occlusion (MCAo) mice (1 hour after reperfusion, 3 hours after MCAo probe insertion), and also used to treat LPS-stimulated microglial BV-2 cells (1, 2, $5{\mu}g/mL$). Markers of inflammation were monitored. Results: NO declined statistically significantly in BVP treated MCAo mice compared to the untreated MCAo group (p < 0.05). Compared to the MCAo group, the BVP-treated MCAo group showed a decreased production volume of malondialdehyde, but an increased glutathione/oxidized glutathione ratio. Compared to the untreated MCAo group, the BVP treated MCAo group showed a statistically significant decline in TNF and $IL-1{\beta}$ levels (p < 0.05). BVP inhibited the levels of p65, p50, $p-I{\kappa}B-{\alpha}$, and levels of p-ERK1/2, p-JNK2, p-P38 declined. Conclusion: BVP is effective at dampening the inflammatory response in vivo and in vitro and may supplement rt-PA treatment.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.295-300
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• 2014

The actin cytoskeleton plays an important role in macrophage-mediated inflammatory responses by modulating the activation of Src and subsequently inducing nuclear factor (NF)-${\kappa}B$ translocation. In spite of its critical functions, few papers have examined how the actin cytoskeleton can be regulated by the activation of toll-like receptor (TLR). Therefore, in this study, we further characterized the biological value of the actin cytoskeleton in the functional activation of macrophages using an actin cytoskeleton disruptor, cytochalasin B (Cyto B), and explored the actin cytoskeleton's involvement in morphological changes, cellular attachment, and signaling events. Cyto B strongly suppressed the TLR4-mediated mRNA expression of inflammatory genes such as cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-${\alpha}$, and inducible nitric oxide (iNOS), without altering cell viability. This compound also strongly suppressed the morphological changes induced by lipopolysaccharide (LPS), a TLR4 ligand. Cyto B also remarkably suppressed NO production under non-adherent conditions but not in an adherent environment. Cyto B did not block the co-localization between surface glycoprotein myeloid differentiation protein-2 (MD2), a LPS signaling glycoprotein, and the actin cytoskeleton under LPS conditions. Interestingly, Cyto B and PP2, a Src inhibitor, enhanced the phagocytic uptake of fluorescein isothiocyanate (FITC)-dextran. Finally, it was found that Cyto B blocked the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at 1 min and the phosphorylation of heat shock protein 27 (HSP27) at 5 min. Therefore, our data suggest that the actin cytoskeleton may be one of the key components involved in the control of TLR4-mediated inflammatory responses in macrophages.

• 한국식품영양학회지
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• 제28권3호
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• pp.343-350
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• 2015

Lonicera japonica 에탄올 추출물의 처리에 의하여 LPS에 의해서 활성화된 RAW 264.7 세포에서 NO의 생성량과 TNF-${\alpha}$, IL-$1{\beta}$ 및 IL-6와 같은 염증성 사이토카인의 분비를 억제하였고, MAPK family인 ERK, p38 및 JNK의 인산화와 $I{\kappa}-B{\alpha}$의 분해를 억제하였다. LPS로 유도한 endotoxin shock 동물실험에서 Lonicera japonica 에탄올 추출물 20 mg/kg에서 LPS로 유도한 endotoxin shock에 대한 생존율을 3배 이상 증가시켰으며, 생존시간도 1.3~1.4배 증가시켰다.

• Molecules and Cells
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• 제26권6호
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• pp.583-589
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• 2008

In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-$1{\alpha}$ ($MIP-1{\alpha}$) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and $MIP-1{\alpha}$ induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of $NF-{\kappa}B$. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.

• 한국식품저장유통학회지
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• 제24권8호
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• pp.1149-1157
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• 2017

본 연구에서는 넓패 에탄올 추출물의 항염증 효과를 알아보기 위해 RAW 264.7 세포에 LPS로 유도된 염증 반응 in vitro 및 in vivo 실험을 실시하였다. RAW 264.7 세포에 LPS와 함께 세포를 배양하였다. 먼저 MTT assay 실험을 통해 넓패 에탄올 추출물이 모든 농도(0.1, 1, 10, 50, $100{\mu}g/mL$)에서 세포독성을 나타내지 않는 것을 학인 하였다. 또한 모든 농도에서 염증억제 효과를 살펴 본 결과, LPS 처리구는 iNOS, COX-2, NF-${\kappa}B$ 그리고 MAPKs의 발현양을 증가 시켰으나, 넓패 에탄올 추출물의 경우 염증 반응에 관여하는 전사인자인 NF-${\kappa}B$와 MAPKs의 활성을 억제함으로써 항염증 효과를 나타내었다. 마지막으로 넓패 에탄올 추출물의 mast cell의 피부 조직학적 변화를 알아본 결과, control의 경우 진피와 경피의 면적이 확장 되어있고, mast cell의 침윤이 정상 군에 비하여 현저하게 증가함을 알 수 있었다. 반면에 넓패 에탄올 추출물의 경우 대조군에 비해 진피와 경피의 두께가 줄었으며 mast cell의 침윤감소에 효과가 있는 것을 확인하였다. 따라서 모든 결과를 종합하였을 때 넓패 에탄올 추출물이 항염증 치료제 뿐만 아니라 더 나아가 항염증에 유용한 기능성 식품소재로써 가치가 높다고 사료된다.

• 한국식품영양과학회지
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• 제46권5호
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• pp.537-544
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• 2017

본 연구에서는 참까막살 에탄올 추출물(PAEE)의 항염증 활성을 확인하기 위하여 LPS로 자극된 RAW 264.7 세포에서의 pro-inflammatory cytokine 및 NO의 분비 생성량과 western blot으로 단백질 발현량을 측정하였다. 또한, croton oil로 유도된 귀 부종 모델을 이용하여 알아보았다. RAW 264.7 세포에서 PAEE를 $0.1{\sim}100{\mu}g/mL$ 농도로 처리 시 세포독성을 나타내지 않음을 확인하였다. 그 결과 PAEE는 pro-inflammatory cytokine(IL-6, $TNF-{\alpha}$, $IL-1{\beta}$) 및 NO의 분비량을 농도 의존적으로 억제시켰으며, iNOS와 COX-2의 발현량도 감소시킴을 확인하였다. 이러한 항염증 활성결과는 $NF-{\kappa}B$와 MAPKs 전사인자의 활성 억제에 의한 것으로 확인되었다. 또한, croton oil로 유도된 귀 부종 모델에서 PAEE를 50 mg/kg body weight 처리 시 귀 부종이 prednisolone(10 mg/kg body weight)과 유사한 정도로 억제됨을 확인하였다. 귀 조직 관찰에서도 PAEE는 croton oil에 의해 증가한 진피와 경피의 두께를 감소시켰으며, 진피로 침윤된 mast cell의 수도 감소시켰다. 이 결과를 종합해 보면 참까막살 에탄올 추출물은 $NF-{\kappa}B$와 MAPKs의 활성화 억제를 통해 염증 매개 물질의 생성을 억제시켜 항염증 활성을 나타내는 것으로 확인되었다.

• Advances in Traditional Medicine
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• 제7권3호
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• pp.235-243
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• 2007

Anemarrhenae Rhizoma (AR) is used in traditional oriental medicine for various medicinal purposes. However, the exact mechanism that accounts for the anti-allergy and anti-inflammatory effects of the AR is still not fully understood. The aim of The present study is to elucidate whether and how AR modulates the allergic reactions in vivo, and inflammatory reaction in vitro. In this study, we showed that AR significantly decreased compound 48/80-induced systemic anaphylaxis, paw oedema, and histamine release from preparation of rat peritoneal mast cells. Also, AR inhibited the expression of inflammatory cytokine in PMA plus A23187-stimulated human mast cells (HMC-1). In addition, we showed that anti-inflammatory mechanism of AR is through suppression of nuclear factor-${\kappa}B$ activation $I{\kappa}B-{\alpha}$degradation. These results provided new insight into the pharmacological actions of AR as a potential molecule for therapy of inflammatory allergic diseases.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.115-127
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• 2009

Samsoeum (SSE) is used in traditional oriental medicine for various medicinal purposes. However, the exact mechanism that accounts for the anti-allergy and anti-inflammatory effects of the SSE is still not fully understood. The aim of the present study is to elucidate whether and how SSE modulates the allergic reactions in vivo, and inflammatory reaction in vitro. In this study, we showed that SSE significantly decreased compound 48/80-induced systemic anaphylaxis, ear-swelling response, histamine release from preparation of rat peritoneal mast cells and anti-dinitropheny IgE-induced passive cutaneous reaction. Also, SSE inhibited the expression of inflammatory cytokine and cyclooxygenase-2 in PMA plus A23187-stimulated human mast cells (HMC-1). In addition, we showed that anti-inflammatory mechanism of SSE is through suppression of nuclear factor-${\kappa}B$ activation and $I{\kappa}B-{\alpha}$ phosphorylation/degradation in HMC-1. These results provided new insight into the pharmacological actions of SSE as a potential molecule for therapy of inflammatory allergic diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.315-320
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• 2013

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-${\kappa}B$/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.

• 생명과학회지
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• 제29권4호
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• pp.402-409
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• 2019

생삼을 쪄서 건조시킨 홍삼은 전통적으로 사용되고 있는 약재로서 면역, 내분비 및 중추신경계 작용을 증진시키며 염증을 억제하는 효과가 있는 것으로 알려져 있다. 본 연구에서는 그람 양성균의 세포벽 성분인 lipoteichoic acid (LTA)에 의한 염증반응에 홍삼추출액(RGE)이 항염증 효과를 가지는지 관찰하고 그 작용 기전을 연구하였다. BV-2 소교세포에서 RGE는 세포에 독성을 유도하지 않으면서 LTA로 인한 nitric oxide (NO)의 생성과 inducible nitric oxide synthase (iNOS) 발현을 억제하였으며, NF-kB p65의 핵으로의 이동과 IkB-a의 분해 또한 억제하였다. 한편, RGE는 농도의존적으로 heme oxygenase-1 (HO-1)의 발현을 유도하였으며, HO-1 siRNA를 처리했을 때는 RGE가 iNOS의 발현을 억제하지 못하였다. RGE는 HO-1의 발현에 관여하는 전사인자인 nuclear factor E2-related factor 2 (Nrf2)를 핵으로 이동을 촉진시켰다. 또한 RGE에 의한 HO-1의 발현은 phosphatidylinositol-3-kinase(PI-3K) 및 MAPK 억제제에 의해 감소되었으며, RGE가 Akt와 ERK, p38, JNK의 인산화를 유도하였다. 이상의 결과를 종합해보면, RGE는 PI-3K/Akt 및 ERK, p38, JNK 신호전달과정을 통해 HO-1의 발현을 유도함으로써 NO와 같은 염증매개물질의 생성을 억제한다는 것을 알 수 있다. 그러므로 홍삼추출액은 그람 양성균에 의한 신경염증과 염증관련 신경계 질환의 치료제로서 사용될 수 있을 것이라 사료된다.