• 대한융합한의학회지
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• 제6권1호
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• pp.29-36
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• 2024

Objectives: Psoriasis is a common chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and an excessive inflammatory response. Agents that can attenuate keratinocyte hyperproliferation and excessive inflammatory responses are considered potentially useful for the treatment of psoriasis. Daehwangmokdanpitang (DHMDPT) exhibits a broad range of bioactivities, including anti-proliferative and anti-inflammatory effects. This study aims to evaluate the anti-psoriatic potential of DHMDPT in vitro. Methods: HaCaT keratinocytes were stimulated with a mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish an in vitro psoriatic keratinocyte model. Cell viability was measured using the MTT assay. Quantitative real-time PCR (qRT-PCR) was performed to measure the mRNA levels of the hyperproliferative marker gene keratin 6 (KRT6) and inflammatory factors such as IL-6, TNF-α, and IL-23A. Additionally, chemokines including CCL5, CCL2, CCL20, and CXCL1 were measured by qRT-PCR. Results: DHMDPT attenuated M5-induced hyperproliferation, as indicated by a reduction in KRT6 expression in HaCaT keratinocytes. M5 stimulation significantly upregulated the mRNA levels of IL-6, TNF-α, and IL-23A. However, DHMDPT treatment attenuated the upregulation of IL-6 but not TNF-α or IL-23A. Additionally, DHMDPT inhibited the expression of CCL5, CCL2, and CXCL1, but not CCL20. Conclusion: DHMDPT effectively attenuated the M5-induced proliferation and inflammatory response in HaCaT keratinocytes. Therefore, DHMDPT could be an attractive candidate for future development as an anti-psoriatic agent.

• Journal of Oral Medicine and Pain
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• 제24권4호
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• pp.361-374
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• 1999

F. nucleatum is a gram-negative obligate anaerobe which is the principal and most frequent cause of gingival inflammation and is the predominant pathogen isolated in subsequent periodontal breakdown. It is also one of the most numerous bacteria found in subgingival plaque samples from healthy sites; its numbers are about 10-fold greater in plaque from periodontally diseased sites. The purpose of this study is to examine the effects of outer membrane(OM), outer membrane vesicle(OMV), and lipopolysaccharide(LPS) from F. nucleatum ATCC 25586 strain on the growth of human gingival fibroblasts and HOS 941 cells, and on the $TNF-{\alpha}$ production / $TNF-{\alpha}$ mRNA expression of mouse splenocytes. For the examination of cytotoxic effects, $TNF-{\alpha}$ production and $TNF-{\alpha}$ mRNA expression, the MTT assay, the ELISA and the RT-PCR were performed, respectively. All extracts of F. nucleatum tested were cytotoxic to both of human gingival fibroblasts and HOS 941 cells, and the significant difference of cytotoxic activity among the extracts was not observed. In the effects of these extracts on the $TNF-{\alpha}$ production / $TNF-{\alpha}$ mRNA expression of mouse splenocytes, all extracts of F. nucleatum tested also stimulated the $TNF-{\alpha}$ production / $TNF-{\alpha}$ mRNA expression, but the effects of the OM extracts on the $TNF-{\alpha}$ production / $TNF-{\alpha}$ mRNA expression were higher than those of the OMV and the LPS extracts. The pattern of the $TNF-{\alpha}$ mRNA expression was similar to that of the $TNF-{\alpha}$ production. These results indicate that F. nucleatum seems to contribute to the pathogenesis of periodontal diseases at least by its cytotoxicity, directly and its $TNF-{\alpha}$ production, indirectly.

• 디지털융복합연구
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• 제14권1호
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• pp.321-326
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• 2016

치주질환은 치아주위 조직에 발현된 염증성 질환이다. 전염증성 사이토카인인 $TNF-{\alpha}$는 국소적인 염증이나 전반적인 염증과 관련이 있는 것으로 알려져 있다. 본 연구의 목적은 한국인에서 TNF 유전자 다형성과 전반적 급진성 치주염 간의 관계를 알아보고자 하였다. 연구대상은 실험군이 60명, 대조군이 81명 이었다. 협측에서 DNA를 채취하여 각 제한효소를 이용한 PCR-RFLP에 의해 $TNF-{\alpha}-308$과 -238을 측정하였다. 급진성 치주염 환자에서 $TNF-{\alpha}-308$ 유전자형은 A/A 3.2%, A/G 38.7% 그리고 G/G 82.35%가 나타났으며 대조군에서는 각 9.1%, 45.5%, 45.5%로 유의한 차이를 보이는 결과이다. $TNF-{\alpha}-238$의 대립유전자 2의 빈도는 실험군에서 67.6%, 대조군에서 72.2%로 유의한 차이를 보였다. 이러한 결과에 따르면 $TNF-{\alpha}-308$과 -238의 유전자다변성은 한국인의 급진성치주염과 연관이 있을 것으로 생각된다.

• 생명과학회지
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• 제30권4호
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• pp.343-351
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• 2020

마가목은 한방에서 기침, 천식, 기관지 질환 등의 치료에 이용되고 있다. 본 연구에서는 마가목(sorbus commixta) 수피의 chloroform 분획물로부터 3종의 triterpenoid 화합물과 1종의 coumarin 화합물을 분리하였다. 분리된 화합물의 구조는 MS와 1D-, 2D-NMR분석에 의해 확인하였으며, 이들은 lupeol, β-sitosterol, ursolic acid와 scopoletin으로 구조동정되었다. 분리된 화합물 중 scopoletin은 마가목에서 처음으로 분리된 화합물이다. Scopoletin은 식물에 널리 분포하고 있는 물질로써 항염증 활성을 가진 기능성 화합물이다. 분리된 화합물들의 혈관 염증 억제에 대한 효과를 평가하기 위해 in vitro에서 LDL 산화 억제능을 평가한 결과, 분리된 화합물 중 scopoletin (IC₅₀=10.2 μM)이 강한 억제 활성을 나타내었다. TNF-α로 활성화된 인체혈관내피세포(EA.hy926)를 이용한 실험에서 scopoletin은 세포부착인자인 ICAM-1, VCAM-1, E-selectin의 발현을 저해하였고, THP-1 단핵구와 EA.hy926 혈관내피세포 간의 부착력도 약화시켰다. 뿐만 아니라, scopoletin은 TNF-α로 유도된 NF-κB 전사인자의 핵내 이동 및 IκBα의 인산화도 저해하였다. 따라서 마가목 추출물로부터 분리된 scopoletin은 NF-κB 신호전달의 억제를 통해 세포부착인자의 발현을 감소시키고, 단핵구의 혈관내피세포로의 부착을 억제시켜 혈관내 항염증 활성을 나타내었다. 이러한 실험결과, scopoletin은 혈관염증 반응으로부터 유도되는 죽상동맥경화증 치료를 위한 후보소재로서 이용될 가능성이 있다고 사료된다.

• 동의생리병리학회지
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• 제17권4호
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• pp.1101-1111
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• 2003

Our study shows that EC extract has inhibitory effect on pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, iNOS and COX2 in hFLSs. IL-1β, IL-6, iNOS and COX2 mRNA expression is suppressed at a low dasage (1㎍/ml) of EC extract. TNF-α was also suppressed at higher dosages (10 ㎍/ml, 100㎍/ml). EC extract also inhibited TNF-α, IL-1β and IL-6 production in pro-inflammatory cytokine stimulated-hFLSs. Expecially IL-1β(p<0.05) production are suppressed significantly. On the other hand, EC extract did not show any cytotoxicity. Thses data suggest that EC extract has anti-inflammatory effect mostly by inhibiting IL-1β production, and thus could be used to prevent or treat some inflammatory disease such as RA. It remains to be known what are the major components responsible for anti-inflammatory effect and what is the main mechanism.

• 대한의생명과학회지
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• 제10권4호
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• pp.341-346
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• 2004

Tumor necrosis factor-α (TNF-α) or its mRNA expression are increased in acute nephrosis of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-α production, provides a protective effect against hypoxia-induced cell injury in rabbit renal cortical slices. To induce hypoxia-induced cell injury, renal cortical slices were exposed to 100% N₂ atmosphere. Control slices were exposed to 100% O₂ atmosphere. The cell injury was estimated by measuring lactate dehydrogenase (LDH) release and p-aminohippurate (PAH) uptake. Exposure of slices to hypoxia increased the LDH release in a time-dependent manner. However, when slices were exposed to hypoxia in the presence of PTX, the LDH release was decreased. The protective effect of PTX was dose-dependent over the concentrations of 0.05∼1 mM. Hypoxia did not increase lipid peroxidation, whereas an organic hydroperoxide t-butylhydroperoxide (tBHP) resulted in a significant increase in lipid peroxidation. PTX did not affect tBHP-induced lipid peroxidation. Hypoxia decreased PAH uptake, which was significantly attenuated by PTX and glycine. tBHP-induced inhibition of PAH uptake was not altered by PTX, although it was prevented by antioxidant deferoxarnine. The PAH uptake by slices in rabbits with ischemic acute renal failure was prevented by PTX pretreatment. These results suggest that PTX may exert a protective effect against hypoxia-induced cell injury and its effect may due to inhibition of the TNF-α production, but not by its antioxidant action.

• 한국해양바이오학회지
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• 제15권1호
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• pp.12-23
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• 2023

Sargassum horneri (SH), a brown macroalgae, has medicinal properties. The present study investigated the immune-enhancing effects of SH extract on peritoneal macrophages (PM). The SH significantly increased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in PM. It was confirmed that SH significantly increased NO expression through the increase of iNOS protein expression, which is the up-regulation pathway. Additionally, it was determined if SH activates the mitogen-activated protein kinase (MAPK) pathway, an upper regulatory mechanism that influences TNF-α, IL-6, and NO expression. Consequently, SH significantly increased the phosphorylation of p38, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK), all of which are MAPK pathway proteins. Moreover, the immune-enhancing effects of SH on another macrophage cell line, bone marrow-derived macrophages were investigated. It was observed that SH significantly enhanced TNF-α, IL-6, and NO production. Overall, this study demonstrates the immune-enhancing effects of SH on macrophages via activated MAPK pathway. Therefore, it suggests that SH has the potential to improve immunological activity in various macrophage cell lines and can be useful as an immune-enhancing treatment.

• 한국식품과학회지
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• 제53권6호
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• pp.722-730
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• 2021

본 연구는 인삼열매로부터 RG-II 형태의 다당(GBW-II)을 분리하고 대식세포 활성화에 대한 세포 내 신호전달의 세부 기작을 규명함으로써 새로운 건강기능성식품 소재 개발을 위한 기초자료를 제시하고자 진행되었다. GBW-II의 구성당을 확인한 결과, 전형적인 RG-II의 구성당인 2-methyl-xylose, apiose, aceric acid, KDO 및 DHA와 같은 특이 구성당을 함유함을 확인할 수 있었다. GBW-II는 대식세포 유래 세포주인 RAW 264.7 cell에 처리하였을 경우, 어떠한 세포 독성도 확인되지 않았으나 IL-6와 TNF-α와 같은 cytokine의 분비는 농도 의존적으로 증가시키는 것으로 나타났다. 또한 RAW 264.7 cell을 이용한 세포 내 신호전달에 관한 실험 결과들을 종합해 볼 때, GBW-II는 대식세포 표면에 발현된 TLR2, TLR4 및 SR에 결합하여 MAPKs (p38, ERK) 및 NF-κB를 경유하여 IL-6와 TNF-α와 같은 cytokine의 분비를 증가시키는 것으로 최종 확인되었다. 한편, RG-I, RG-II, β-glucan, arabinoxylan 및 xyloglucan과 같은 식물체 유래 고분자 다당체의 약리활성은 그들의 구조적 차이에서 기원하는 것으로 알려져 있기 때문에 건강기능성식품 소재로의 개발을 위해서는 활성물질의 미세구조에 대한 해명이 필수적이라 할 수 있다. 따라서 본 연구진은 추후 연구에서 효소적 및 화학적 가수분해, methylation, sequencing 등을 이용하여 인삼열매 유래 정제 다당 GBW-II의 미세구조를 규명하고자 한다.

• 대한한방부인과학회지
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• 제36권3호
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• pp.1-24
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• 2023

Objectives: Boeum-jeon (BEJ) is a herbal formula composed 8 Korean medicinal herbs and is traditionally used to treat inflammatory diseases. In this study, the authors tried to confirm the antioxidant efficacy of BEJ and its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methods: In this experiment, results of BEJ on the following two were measured as follows: (1) Antioxidant effects was measured by DPPH Radical scavenging Activity, ABTS Radical scavenging Activity. (2) Anti-Inflammatory effects were evaluated by the production amount of ROS, NO, Cytokine (PGE2, IL-1β, IL-6, TNF-α), COX-2, iNOS, TNF-α, IL-1β, IL-6, HO-1, NQO1 (the previous seven are "mRNA Expression"), COX-2, iNOS, TNF-α, IL-1β, IL-6, HO-1, NQO1, NRF2 (the previous eight are "Protein Expression") ERK, JNK, p38 (the previous three are "Protein Phosphorylation") in LPS-stimulated RAW 264.7 cells. Results: The experimental measurement results are as follows: (1) DPPH Radical scavenging Activity, ABTS Radical scavenging Activity increased in a concentration -dependent manner in the BEJ-treated group. (2) As a result of measuring anti-inflammatory efficacy, the production of ROS, NO, and Cytokine (PGE2, TNF-α, IL-1β, IL-6) in the BEJ-administered group was significantly reduced compared to the control group. (3) Among mRNA Expression levels, COX-2, iNOS, IL-1β, IL-6 and TNF-α was significantly decreased in a concentration-dependent manner than in the control group, and HO-1 and NQO1 were significantly increased in a concentration -dependent manner than in the control group. (4) Among the Protein Expression levels, COX-2, iNOS, IL-1β, IL-6 and TNF-α was significantly decreased in a concentration -dependent manner compared to the control group, and HO-1, NQO1 and NRF2 was significantly increased in a concentration-dependent manner compared to the control group. (5) As a result of Protein Phosphorylation, ERK, p38 and JNK was significantly decreased compared to the control group in a concentration-dependent manner. Conclusions: Boeum-jeon has been experimentally confirmed to have antioxidant and anti-inflammatory effects, and if the evidence for efficacy is reinforced through further studies such as in vivo studies and clinical trials in the future, it can be effectively used to treat various inflammatory diseases such as bladder inflammation and chronic pelvic inflammation.

• 한국체육학회지인문사회과학편
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• 제54권5호
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• pp.769-780
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• 2015

이 연구는 고령자의 근육수축양식 및 손상정도에 따른 염증물질, 면역적격세포 및 골수유래 전구세포의 변화를 검증하는데 그 목적이 있다. 연구대상은 최근 6개월간 저항성운동 프로그램을 실시하지 않은 65세 이상의 고령자 20명을 신장성운동 집단(ECC, n=10)과 단축성운동 집단(CON, n=10)으로 분류하였다. 모든 피험자는 팔꿈치 굽힘근의 1차 신장성운동(ECC 1) 및 단축성운동(CON)을 실시하였고, ECC는 4주후에 재차 2차 신장성운동(ECC 2)을 6회 10세트, 세트 사이에 2분의 휴식시간을 적용하여 실시하였다. 골격근손상 지표(ROM, VAS, CK), 염증물질(TNF-α, IL-1, IL-6), 면역적격세포(CD3+, CD4+, CD8+, CD19+), 골수유래 전구세포(CD34+) 및 백혈구수는 운동전, 운동 직후, 운동 시기의 2, 24, 48, 72 및 96시간 후에 각각 측정하였다. 주요결과는 다음과 같다. 고령자의 골격근손상 지표(ROM, VAS)는 CON(근육수축양식) 및 ECC 2(손상정도)와 각각 비교해서 ECC 1에서 손상이 크게 증가하였다(p<.05). IL-6 및 TNF-α는 CON 및 ECC 2와 각각 비교해서 ECC 1의 24, 48 및 72시간 후에 유의하게 높게 나타났다(p<.05). 호중구수는 CON 및 ECC 2와 각각 비교해서 ECC 1의 2시간 후에 유의하게 높게 나타났다(p<.05). 이 연구에서는 고령자에서도 근육수축양식은 단축성운동보다 신장성운동에서, 또한 손상정도는 2차 신장성운동보다 1차 신장성운동에서 보다 크게 손상이 발생하였다는 사실을 확인하였다. 특히 IL-6와 TNF-α 및 호중구수는 근손상 정도와 밀접한 관련성이 있다는 것이 시사되었다.