• 대한의생명과학회지
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• 제26권3호
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• pp.192-200
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• 2020

Natural products have received revived interest via traditional remedies or alternative medicine used for the treatment of various diseases. Zanthoxylum piperitum (ZP) has been utilized in traditional medicine for various medicinal purposes. The present study was conducted to evaluate whether ZP modulates allergic inflammation both in vivo and in vitro. We examined the pharmacological effects of ZP on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) symptoms in mice. Additionally, in order to clarify the anti-inflammatory mechanisms of ZP, we elucidate the effect of ZP on the expression levels of inflammatory cytokines and nuclear factor-κB (NF-κB) in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The results demonstrated that ZP attenuated AD clinical symptoms such as erythema, edema and dryness as well as histamine and IgE serum levels in DNCB-induced AD model mice. Additionally, ZP suppressed the expression of inflammatory cytokines and activation of NF-κB in AD-like skin lesions and stimulated HMC-1. These results provide experimental evidence that ZP may be useful candidate for treating allergic inflammation including AD.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1443-1446
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• 2018

In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ) could alleviate cholinergic memory impairment in mice. Oral administration of LJ alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression and CREB phosphorylation in the hippocampi of the brain, as well as suppressed $TNF-{\alpha}$ expression and $NF-{\kappa}B$ activation. LJ also increased BDNF expression in corticosterone-stimulated SH-SY5Y cells and inhibited $NF-{\kappa}B$ activation in LPS-stimulated microglial BV2 cells. However, LJ did not inhibit acetylcholinesterase activity. These findings suggest that LJ, a member of human gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF expression and inhibiting $NF-{\kappa}B$ activation.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.428-433
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• 2015

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.540-545
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• 2022

Betulin is a triterpenoid natural product contained in several medicinal plants including Betulae Cortex. These medicinal plants have been used for controlling diverse inflammatory diseases in folk medicine and betulin showed anti-inflammatory, antioxidative, and anticancer activities. In this study, we tried to examine whether betulin exerts a regulative effect on the gene expression of MUC5AC mucin under the status simulating a pulmonary inflammation, in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with betulin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h or the indicated periods. The MUC5AC mucin mRNA expression and mucin glycoprotein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. To elucidate the action mechanism of betulin, effect of betulin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated by western blot analysis. The results were as follows: 1) Betulin significantly suppressed the production of MUC5AC mucin glycoprotein and down-regulated MUC5AC mRNA expression induced by PMA in NCI-H292 cells. 2) Betulin inhibited NF-κB activation stimulated by PMA. Suppression of inhibitory kappa B kinase (IKK) by betulin led to the inhibition of the phosphorylation and degradation of inhibitory kappa B alpha (IκBα), and the nuclear translocation of NF-κB p65. This, in turn, led to the down-regulation of MUC5AC glycoprotein production in NCI-H292 cells. These results suggest betulin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

• 한국유기농업학회지
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• 제28권4호
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• pp.659-677
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• 2020

본 실험에서는 익모초 지상부 에탄올 추출물의 항산화 및 항염증 효과를 확인하여 건강 기능성 소재로서의 가능성을 평가하고자 하였다. DPPH 및 ABTS radical 소거 활성, 환원력, 총 폴리페놀 및 플라보노이드 함량을 통해 익모초의 항산화능을 측정한 결과, 400 ㎍/mL, 1500 ㎍/mL의 농도에서 57.8%, 62.3%의 DPPH 및 ABTS radical 소거활성을 보였고 환원력 또한 농도 의존적으로 증가하는 경향을 보였다. 총 폴리페놀 함량 및 플라보노이드 함량은 1 mg/mL의 농도에서 각각 51.40 ± 0.47 mg of gallic acid equivalents/g, 73.28 ± 0.10 mg of rutin equivalents/g로 나타났으며, 익모초 추출물은 세포 내 ROS의 생성 억제에 있어서 유의적인 효과를 보였다. 익모초의 항염증 효과를 측정한 결과, LPS로 자극해 활성화된 RAW 264.7 cell에서 익모초 추출물(0~400 ㎍/mL)의 세포 독성은 없었으며 LPS 처리로 유도된 세포의 형태학적 변화도 농도의존적으로 완화되는 경향을 보였다. NO 발생량은 LPS 처리군과 비교해 익모초 추출물 처리 시 농도 의존적으로 감소하였고, 400 ㎍/mL에서는 90.3%로 NO의 생성이 억제되었다. 염증성 cytokine (TNF-α, IL1-β)의 생성도 유의적으로 감소하였고 NO를 생성하는 염증성 단백질 iNOS의 발현 또한 억제되었으며 이와 같은 염증성 단백질의 전사를 조절하는 NF-κB (NF-κB, IκB-α) 및 MAPK (ERK, p38)의 인산화 및 활성화 또한 익모초 추출물 처리로 인해 억제됨을 확인하였다. 따라서 익모초 추출물은 NF-κB signaling pathway 및 ERK/p38 MAPK cascade pathway의 조절을 통해 염증성 단백질 및 염증인자의 발현을 감소시킨다고 볼 수 있다. 이러한 결과를 토대로 익모초 지상부 에탄올 추출물은 천연 기능성 소재로서 활용될 가능성이 있으며, 본 연구 결과는 익모초의 고부가가치 향상을 위한 기초자료로 도움이 될 것으로 생각된다.

• Parasites, Hosts and Diseases
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• 제62권3호
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• pp.281-293
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• 2024

We previously reported that leukotriene B₄ (LTB₄) contained in Trichomonas vaginalis-derived secretory products (TvSP) play an essential role in interleukin-8 (IL-8) production in human mast cell line (HMC-1 cells) via LTB₄ receptor (BLT)-mediated Nuclear Factor-kappa B (NF-κB) activation. Dynamin, a GTPase, has been known to be involved in endocytosis of receptors for signaling of production of cytokine or chemokines. In the present study, we investigated the role of dynamin-mediated BLT1 endocytosis in TvSP-induced IL-8 production. When HMC-1 cells were transfected with BLT1 or BLT2 siRNA, TvSP-induced IL-8 production was significantly inhibited compared with that in cells transfected with control siRNA. In addition, pretreatment of HMC-1 cells with a dynamin inhibitor (Dynasore) reduced IL-8 production induced by TvSP or LTB₄. TvSP- or LTB₄-induced phosphorylation of NF-κB was also attenuated by pretreatment with Dynasore. After exposing HMC-1 cells to TvSP or LTB₄, BLT1 was translocated from the intracellular compartments to the plasma membrane within 30 min. At 60 min after stimulation with TvSP or LTB₄, BLT1 remigrated from the cell surface to intracellular areas. Pretreatment of HMC-1 cells with dynamin-2 siRNA blocked internalization of BLT1 induced by TvSP or LTB₄. Co-immunoprecipitation experiments revealed that dynamin-2 strongly interacted with BLT1 60 min after stimulation with TvSP or LTB₄. These results suggest that T. vaginalis-secreted LTB₄ induces IL-8 production in HMC-1 cells via dynamin 2-mediated endocytosis of BLT1 and phosphorylation of NF-κB.

• 생명과학회지
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• 제30권1호
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• pp.106-112
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• 2020

아미노아실-트랜스퍼 리보핵산 합성효소-상호작용 다기능 단백질 2(AIMP2)는 여러 tRNA 합성효소들과의 결합체를 이루게 하는 기능을 하며, DNA 손상에 대한 반응으로 세포사멸 활성을 나타낼 수 있다. DNA에 손상이 발생하면 AIMP2는 MDM2 공격으로부터 p53을 보호하기 위해 MDM2에 결합한다. TGF-β 신호에서 AIMP2는 세포 핵으로 들어가 FUSE 결합 단백질(FBP)과 결합하여 c-myc을 억제한다. TNF 수용체 관련 인자 2(TRAF2)는 c-Jun N-말단 키나아제(JNK), NF-κB 및 p38 미토겐 활성화 단백질 키나아제(MAPKs)의 신호에서 실행되는 두 수용체, TNF 수용체 1과 2 사이의 중요한 중재자이다. TARF2는 TNF-α 신호에서 JNK와 NF-κB의 활성화에 필요하며, 세포사멸 신호를 막는 중재자 역할을 수행한다. 또한 TNF-α 신호에서 AIMP2는 세포사멸을 향상시킨다. 이 신호에서, AIMP2는 TRAF2를 분해하는 것으로 잘 알려진 E3 유비키틴 효소인 c-IAP1과의 결합을 향상시킨다. AIMP2, TRAF2 및 c-IAP1을 포함한 복합체의 형성은 proteasome을 매개로 하여 TRAF2의 분해를 초래한다. 이러한 연구 결과는 AIMP2가 TNF-α 신호에서 직접적인 상호작용을 통해 TRAF2를 하향 조절시켜 세포사멸을 유도할 수 있음을 시사한다.

• 한국식품과학회지
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• 제52권2호
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• pp.138-143
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• 2020

본 연구에서는 다양한 만성 대사성 질환에 기초적 유발 기전인 산화적 스트레스 및 염증에 대한 폴리페놀 함유 블랙 초크베리의 보호 효과를 살펴보았다. 블랙 초크베리는 DPPH, ·OH, 및 NO 등 다양한 라디컬 소거능을 나타냈다. 내독소인 LPS에 의해 활성화된 대식세포 내 ROS 증가는 폴리페놀 함유 블랙 초크베리에 의해 감소하였다. 이는 블랙 초크베리가 전사인자인 NRF2의 핵 내 이동 및 이로 인해 조절되는 SOD에 의한 ROS 소거능 및 NOX2에 의한 ROS 생성 저하에 의한 것으로 나타났다. 블랙 초크베리의 염증 보호 효과는 활성화된 대식세포에서 증가하는 NF-κB의 핵 내 이동에 따른 COX-2, iNOS와 같은 염증 매개인자 관련 효소와 TNF-α, IL-6, IL-1β와 같은 염증성 사이토카인의 저하에 의한 것으로 나타났다. 결론적으로 블랙 초크베리의 산화적 스트레스 및 염증 보호 효과는 항산화 효소 관련 전사 인자인 NRF2 조절 기전 및 염증 관련 전사 인자인 NF-κB와 관련 유전자 발현의 조절을 통하여 나타났다. 추후 블랙 초크베리 내 기능성 물질에 대한 심도 있는 기전 연구를 통해 천연물 유래 기능성 소재로서의 역할을 할 것으로 판단된다.

• International Journal of Internet, Broadcasting and Communication
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• 제12권3호
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• pp.139-148
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• 2020

Red rose petals are usually disposed but they are an abundant source of phenolics and traditionally used as food supplement and as herbal medicine. Of the Various phenolics, they are known to have anticancer, antioxidant, and anti-inflammatory properties. In this study, we investigated the anti-inflammatory effects of red rose ethanolic extracts (GRP) on lipopolysaccharide (LPS)-activated RAW 264.7 cells. The results demonstrated that pretreatment of GRP (500㎍/mL) significantly reduced NO production by suppressing iNOS protein expression in LPS-stimulated cells. Anti-inflammatory effects by red rose petals were observed in the following. Red rose petals inhibited the translocation of NF-κB from the cytosol to the nucleus via the suppression of IκB-α phosphorylation and also inhibited LPS-stimulated NF-κB transcriptional activity. These findings suggest that red rose petals exert anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of red rose petals. Therefore, red rose petals could be regarded as a potential source of natural anti-inflammatory agents.

• Molecules and Cells
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• 제20권3호
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• pp.364-370
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• 2005

We show that sulforaphane inhibits osteoclastogenesis in the presence of macrophage colony-stimulating factor (M-CSF) and receptor for activation of nuclear factor-${\kappa}B$ ligand (RANKL) in osteoclast (OC) precursors. Sulforaphane, an aliphatic isothiocyanate, is a known cancer chemo-preventative agent with anti-oxidative properties. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$) is a critical transcription factor in RANKL-induced osteoclastogenesis, and electrophoretic mobility shift assays (EMSAs) and assay of NF-${\kappa}B$-mediated secreted alkaline phosphatase (SEAP) revealed that sulforaphane selectively inhibited NF-${\kappa}B$ activation induced by RANKL. Inhibition may involve interaction of sulforaphane with thiol groups, since it was prevented by reducing agents.