• Nutrition Research and Practice
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• 제15권6호
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• pp.686-702
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• 2021

BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E₂ (PGE₂), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE₂, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

• 생명과학회지
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• 제29권7호
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• pp.809-816
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• 2019

p-Coumaric acid (p-CA)는 항산화 및 항염 활성을 가진 식물계에서 가장 풍부한 식물화학물질이다. 그러나 위암세주포에서 p-CA의 항암 활성과 전사체 발현에 대한 연구는 아직까지 수행된 바 없다. 본 연구에서는 SNU-16 위암세포에서 p-CA에 의한 세포 증식 억제 및 전사체 프로파일에 미치는 영향을 조사하였다. p-CA는 세포사멸 단백질 발현을 조절하여 SNU-16 세포에서의 세포사멸을 유도하였다. RNA-seq 분석을 사용하여 p-CA처리에 의해 SNU-16 세포에서 차별적으로 발현된 유전자(DEGs)를 동정하였다. DEGs들의 gene ontology (GO) 술어로 유전자 산물을 검색한 결과, 주로 염증반응, 세포사멸 과정, 세포주기 및 면역 반응에 관여하는 생물학적 과정에 관여하는 것으로 나타났다. 또한, KEGG 경로분석 결과, p-CA는 주로 PI3K-Akt 와 암 신호전달 경로에 변화를 유발하였다. 본 연구결과는 p-CA가 세포증식과 암 신호 전달 경로에 관여하는 유전자 발현을 조절함으로써 위암 예방 효과를 나타낼 수 있음을 시사한다.

• BMB Reports
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• 제49권11호
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• pp.641-650
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• 2016

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

• BMB Reports
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• 제48권10호
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• pp.549-558
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• 2015

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

• Nutrition Research and Practice
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• 제17권4호
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• pp.641-659
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• 2023

BACKGROUND/OBJECTIVES: The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage. MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. RESULTS: ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. CONCLUSIONS: Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

• Molecules and Cells
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• 제46권3호
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• pp.133-141
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• 2023

Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.

• 한국가금학회지
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• 제48권3호
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• pp.111-122
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• 2021

최근에 IL-34가 MCSFR에 대한 두 번째 기능적 리간드로 확인되었으며, M-CSFR에 대한 결합을 통해 IL-34는 M-CSF와 유사한 기능을 공유한다. 지금까지 닭의 IL-34에 대한 실험적 연구가 아닌 예측된 서열로만 보고되었으며, 닭의 IL-34 기능에 대한 정보는 아직 부족하다. 닭 IL-34의 잠재적 생물학적 기능을 구명하기 위하여, 다양한 품종의 닭, 세포주에 대한 괴사성 장염, 살모넬라 및 E. coli 유래의 LPS 등을 처리하여 관찰하였다. 또한 닭의 IL-34와 M-CSF 재조합 단백질 생산 및 이를 이용한 전염증성 사이토카인 유도를 위하여 클로닝 및 재조합 단백질을 발현 및 정제하였다. 특히 관절이상 육계(unknown cause)에 대한 IL-34, M-CSF, 그리고 M-CSFR 유전자의 발현이 대조구보다 유의하게 증가하였으나, 병원균 자극 조직의 경우 많은 조직에서 감소함을 보였다. M-CSFR의 발현은 in vitro에서 IL-34와 M-CSF 재조합 단백질에 의해 증가함을 보였으며, IFN-γ은 재조합 단백질 M-CSF을 제외한 IL-34에 의해 증가하였다. 하지만, IL-12 발현은 유의적인 차이가 없었으며, IL-1β의 경우는 감소하였다. 이 결과는 IL-34와 M-CSF가 고전적인 대식세포와 대체 대식세포 모두에서 역할을 한다고 할 수 있다. 결론적으로, in vitro와 in vivo 실험을 통하여 병원균 처리 시 닭의 IL-34 발현을 관찰하였으며, IL-34 재조합 단백질이 대식세포에서와 전염증성과 항염증성 반응에 중요한 역할을 함을 증명하였다. 추후에 IL-34의 사이토카인, 케모카인 그리고 염증반응 경로 등에 대한 추가 연구가 필요하다고 판단된다.

• IMMUNE NETWORK
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• 제9권6호
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• pp.255-264
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• 2009

Background: Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine. Methods: We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change. Results: LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naive macrophages, through the treatment with high concentrations of cordycepin ($40{\mu}g/ml$). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and chemokines (CX3CR1, RANTES), such as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-${\beta}$) were up-regulated by both cordycepin and adenosine. Conclusion: Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.

• 한국약용작물학회지
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• 제24권1호
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• pp.31-37
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• 2016

Background : We studied the anti-oxidant activity and anti-inflammatory effects of Spiraea fritschiana Schneid extract (SFSE). Methods and Results : The SFSE was prepared using methanol and was evaluated for its total phenol and flavonoid content, DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical scavenging activity, reducing power, and effect on nitric oxide (NO) production, and cell viability by using real-time polymerase chain reaction (PCR). The total phenol content was $212.78{\mu}g{\cdot}galli$c acid equivalent (GAE)/mg and the total flavonoid content was $66.84{\mu}g{\cdot}quercetin$ equivalent (QE)/mg. The extract showed antioxidant activity (DPPH free-radical scavenging activity) with $RC_{50}$ value of $76.61{\mu}g/m{\ell}$. The reducing power of the extract was Abs 0.58 at $250{\mu}g/m{\ell}$. Cell viability was determined using the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To evaluate anti-inflammatory activity, we examined the inhibitory effects on lipopolysaccharide-(LPS)-induced NO production in RAW 264.7 cells. The NO inhibition rate was 90% at $200{\mu}g/m{\ell}$ SFSE. At the same concentration, the expression of pro-inflammatory genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 also decreased. Conclusions : Our results suggest that SFSE is a novel resource for the development of foods and drugs that possess anti-oxidant and anti-inflammatory activity.

• 생명과학회지
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• 제24권8호
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• pp.843-850
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• 2014

본 연구에서는 전통주 제조시 부산물로 생산되는 주박과 누룩으로부터 추출물과 유기용매 분획물을 총 85종을 제조하고, 이들에 의한 항염증 활성을 연구하였다. 85종의 분획물 중 선별한 세 가지의 분획물(KSD-E1-3, KSD-E2-3, KSD-E4-3)에 의해서 LPS에 의해 염증이 유도된 RAW 264.7 세포주에서 nitric oxide 생산이 현저히 감소됨을 확인하였다. 또한, 세가지 분획물에 의해 염증유발 유전자인 COX-2, TNF-alpha, 그리고 iNOS 유전자의 발현이 감소되었다. 세 가지 분획물 중 KSD-E4-3에 의한 항염증 활성의 작용기전을 이해하기 위하여 oligo DNA microarray를 수행하였다. 마이크로어레이 결과 발현이 감소된 유전자 중 염증과 관련된 유전자 6개(IL-1F6, iNOS, IL-10, Fabp4, IL-1RN, CSF2)를 선택하여, RT-PCR과 정량적 real-time PCR을 수행하였다. 그 결과, 모든 유전자의 발현이 감소됨을 확인하였다. 결론적으로, 이러한 연구결과는 전통주 주박이 항염증 활성을 가지고 있는 식품이나 약품을 개발하는데 필요한 새로운 자원으로서 활용 가능함을 시사하는 것이다.