• Korean Journal of Acupuncture
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• 제30권4호
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• pp.243-251
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• 2013

Objectives : Bower Actinidia has been widely used for treatment of inflammatory diseases, such as jaundice, cystolithiasis. However, the mechanism of its anti-inflammatory activity has not been clarified. In this study, we investigated the inhibitory effect of Bower Actinidia pharmacopuncture extract(BA) on LPS-induced inflammation. Methods : The effect of BA was analyzed by ELISA, RT-PCR and Western blotting in LPS-stimulated RAW264.7 cells. Results : We found that BA suppressed not only the mRNA expression of pre-inflammatory cytokines, cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS), but also the phosphorylation of ERK, JNK and p38. Conclusions : These results suggest that BA exerts an anti-inflammatory effect through the regulation of the mitogen-activated protein kinase(MAPK) pathway, thereby decreasing production of pre-inflammatory cytokines.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10819-10824
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• 2015

Aims: To explore the effect and probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethylphenyl ester (ATPR) on apoptosis of MDA-MB-231 breast cancer cells. Materials and Methods: MTT assays were performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. Morphologic changes were observed by microscopy. The apoptosis rates and cell cycling of MDA-MB-231 cells treated with ATRA or ATPR were assessed using flow cytometry analysis. Expression of retinoic acid receptor and phosphorylation of ERK, JNK, p38 proteins were detected by Western blotting. Results: Treatment of the cells with the addition of $15{\mu}mol/L$ ATPR for 48 h clearly demonstrated reduced cell numbers and deformed cells, whereas no changes in the number and morphology were observed after treatment with ATRA. The apoptosis rate was 33.2% after breast cancer MDA-MB-231 cells were treated by ATPR ($15{\mu}mol/L$) whereas ATRA ($15{\mu}mol/L$) had no apoptotic effect. ATPR inhibited the phosphorylation of ERK, JNK, and p38 while ATRA had no significant effect. ATPR inhibited the expression of BiP and increased the expression of Chop at the protein level compared with control groups, ATRA and ATPR both decreased the protein expression of $RXR{\alpha}$, ATPR reduced the protein expression of $RAR{\beta}$ and $RXR{\beta}$ while ATRA did not decrease $RAR{\beta}$ or $RXR{\beta}$. Conclusions: ATPR could induce apoptosis of breast cancer MDA-MB-231 cells, possible mechanisms being binding to $RAR{\beta}/RXR{\beta}$ heterodimers, then activation of ER stress involving the MAPK pathway.

• 한국자원식물학회지
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• 제32권6호
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• pp.698-704
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• 2019

Quercus mongolica (QM), which belongs to fagaceae, is one of the oak native to Korea. We evaluated the anti-inflammatory effect of branches extracted with 70% ethanol of QM (QM-B) and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. The QM-B showed anti-inflammatory activity through inhibition of NO production. The QM-B dose-dependently suppressed NO production by inhibiting iNOS, COX-2 and IL-6 expression in LPS-induced RAW264.7 cells. The QM-B inhibited the degradation and phosphorylation of IκB-α and NF-κB activation. The QM-B suppressed the phosphorylation of p38 and ERK1/2. Also, the QM-B increased HO-1 expression. These results suggested that QM-B may utilize anti-inflammatory activity by suppressing NF-κB and MAPK signaling pathway and inducing HO-1 expression indicated that the QM-B can be used as a natural anti-inflammatory drugs.

• 생약학회지
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• 제42권2호
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• pp.175-181
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• 2011

Oxidative stress or accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

• Journal of Microbiology and Biotechnology
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• 제28권3호
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• pp.349-356
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• 2018

Asterias amurensis is a marine organism that causes damage to the fishing industry worldwide; however, it has been considered a promising source of functional components. The present study aimed to investigate the immune-enhancing effects of fatty acids from three organs of A. amurensis on murine macrophages (RAW 264.7 cells). A. amurensis fatty acids boosted production of immune-associated factors such as nitric oxide (NO) and prostaglandin E2 in RAW 264.7 cells. A. amurensis fatty acids also enhanced the expression of critical immune-associated genes, including iNOS, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6, as well as COX-2. Western blotting showed that A. amurensis fatty acids stimulated the $NF-{\kappa}B$ and MAPK pathways by phosphorylation of $NF-{\kappa}B$ p-65, p38, ERK1/2, and JNK. A. amurensis fatty acids from different tissues resulted in different levels of $NF-{\kappa}B$ and MAPK phosphorylation in RAW 264.7 cells. The results increase our understanding of how A. amurensis fatty acids boost immunity in a physiological system, as a potential functional material.

• Journal of Ginseng Research
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• 제46권5호
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• pp.690-699
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• 2022

Background: Few studies reported the therapeutic effect of Korean Red Ginseng (KRG) in lung inflammatory diseases. However, the anti-inflammatory role and underlying molecular in cadmium-induced lung injury have been poorly understood, directly linked to chronic lung diseases (CLDs): chronic obstructive pulmonary disease (COPD), cancer etc. Therefore, in this study we aim to investigate the therapeutic activities of water extract of KRG (KRG-WE) in mouse cadmium-induced lung injury model. Method: The anti-inflammatory roles and underlying mechanisms of KRG-WE were evaluated in vitro under cadmium-stimulated lung epithelial cells (A549) and HEK293T cell line and in vivo in cadmium-induced lung injury mouse model using semi-quantitative polymerase chain reaction (RT-PCR), quantitative real-time PCR (qPCR), luciferase assay, immunoblotting, and FACS. Results: KRG-WE strongly ameliorated the symptoms of CdSO4-induced lung injury in mice according to total cell number in bronchoalveolar lavage fluid (BALF) and severity scores as well as cytokine levels. KRG-WE significantly suppressed the upregulation of inflammatory signaling comprising mitogen-activated protein kinases (MAPK) and their upstream enzymes. In in vitro study, KRG-WE suppressed expression of interleukin (IL)-6, matrix metalloproteinase (MMP)-2, and IL-8 while promoting recovery in CdSO₄-treated A549 cells. Similarly, KRG-WE reduced phosphorylation of MAPK and c-Jun/c-Fos in cadmium-exposed A549 cells. Conclusion: KRG-WE was found to attenuate symptoms of cadmium-induced lung injury and reduce the expression of inflammatory genes by suppression of MAPK/AP-1-mediated pathway.

• Parasites, Hosts and Diseases
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• 제53권4호
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• pp.371-377
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• 2015

Trichomonas vaginalis induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in $TNF-{\alpha}$ production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased $TNF-{\alpha}$ production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, $TNF-{\alpha}$ production was significantly decreased compared to the control; however, $TNF-{\alpha}$ reduction patterns were different depending on the type of PI3K/MAPK inhibitors. $TNF-{\alpha}$ production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of $TNF-{\alpha}$ production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

• 한국발생생물학회지:발생과생식
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• 제23권2호
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• pp.119-128
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• 2019

Melanoma is one of the most aggressive and treatment-resistant malignancies. Antidiabetic drug metformin has been reported to inhibit cell proliferation and metastasis in many cancers, including melanoma. Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). Paclitaxel is currently prescribed for treatment of melanoma. However, paclitaxel induced the activation of ERK/mitogen-activated protein kinase (MAPK) pathway, a cell signaling pathway implicated in cell survival and proliferation. Therefore, we reasoned that combined treatment of paclitaxel with metformin could be more effective in the suppression of cell proliferation than treatment of paclitaxel alone. Here, we investigated the combinatory effect of paclitaxel and metformin on the cell survival in SK-MEL-28 melanoma cell line. Our study shows that the combination of paclitaxel and metformin has synergistic effect on cell survival and suppresses the expression of proteins involved in cancer metastasis. These findings suggest that the combination of paclitaxel and metformin can be a possible therapeutic option for treatment of melanoma.

• 한국식품과학회지
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• 제51권4호
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• pp.361-368
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• 2019

황칠추출분말은 여성호르몬인 에스트로겐과 구조적 유사성을 가진 루틴을 다량 함유하고 있다(황칠추출분말 1g당 11.19 mg의 루틴 함유). 루틴은 식물성 여성호르몬이라고 불리는 플라보노이드 성분의 일종으로, 에스트로겐 수용체를 통한 신호전달을 증가시킨다. 특히 $ER-{\alpha}$로부터 세포내로 전달되는 MAPK/ERK 신호 전달 경로를 활성화시킴으로써, 갱년기의 대표적인 만성증상들을 개선할 수 있는 가능성이 있다고 여겨진다. 본 연구는 루틴이 다량 함유된 황칠추출분말을 폐경의 유도를 위해 난소를 절제한 쥐에 투여하여 여성갱년기 증상의 개선에 미치는 영향을 평가하였다. 그 결과 골교체율 관련 지표로서 폐경기 여성에서 높다고 알려진 오스테오칼신이 감소하는 경향성을 나타냈고, CTX는 유의적인 감소를 나타냈을 뿐만 아니라, 에스트로겐 수용체의 활성화를 증가시키는 경향성을 나타냈다. 이를 통해, 황칠추출분말은 골다공증의 예방 및 개선 효과를 나타내는 갱년기 여성 건강에 도움을 줄 수 있는 기능성 원료로서의 가능성을 보여준다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2495-2499
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• 2015

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation, terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of RCCC and 28 control cases. Expression levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+ FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05). CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors.