• 동의생리병리학회지
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• 제22권5호
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• pp.1299-1303
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• 2008

Since exercise training induces mechanical stress to the heart, we examined the activation pattern of mitogen-activated protein kinase(MAPK)s signaling pathway by immunohistochemistry. The immunoreactions of MAPKs signaling with c-fos and Schiff's reaction were increased in the cardiac muscle of exercised rat compared to normal one except immunoreaction for MEK1/2 and ERK1/2 and p38. However, the immunoreaction of phospho-JNK and phospho-p38 with early gene c-fos were arrested markedly in water extract of Alliium sativum (WEAS) treated rat compared to exercised one. Since MAPKs signaling does play a protective role in response to pathological stimulus in the heart, results in the present study suggest that WEAS may act as a alleviating agent for exercise-induced stress to. heart through regulating MAPKs signaling activation.

• 동의생리병리학회지
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• 제24권3호
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• pp.410-415
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• 2010

The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Belamcanda chinensis (BC) on the RAW 264.7 cells. To evaluate the anti-inflammatory effects of BC, we examined the cytokine productions including nitric oxide (NO), interleukin (IL)-1b, IL-6 and tumor necrosis factor-a (TNF-a) in lipopolysaccharide (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kB) using Western blot. BC inhibited LPS-induced production of NO, IL-6 and TNF-a but not of IL-1b in RAW 264.7 cells. BC respectively inhibited the activation of MAPKs such as c-Jun NH2-terminal kinase (JNK) and p38 but not of extracelluar signal-regulated kinase (ERK 1/2) and NF-kB in the LPS-stimulated RAW 264.7 cells. Taken together, Our results showed that BC down-regulated LPS-induced NO, IL-6 and TNF-a productions mainly through JNK and p38 MAPK pathway.

• 대한한의학회지
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• 제39권4호
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• pp.158-170
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• 2018

Objectives: The objective of this study is Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) and bee venom (BV) to experimental prove comparative study of VCA and BV on the anti-cancer effect and mechanisms of action. Methods: In this study, it was examined in a human hepatocellular carcinoma cell line, Hep G2 cells. Cytotoxic effects of VCA and BV on Hep G2 cells were determined by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay in vitro. VCA and BV killed Hep G2 cells in a time- and dose-dependent manner. Results: The apoptotic cell death was then confirmed by propidium iodide staining and DNA fragmentation analysis. The mechanisms of action was examined by the expression of anti-apoptotic proteins and activation of mitogen-activated protein kinases. Treatment of Hep G2 cells with VCA activated poly (ADP-ribose) polymerase-1 (PARP-1) known as a marker of apoptosis, and mitogen-activated protein kinases signaling pathways including SAPK/JNK, MAPK and p38. BV also activated PARP-1, MAPK, p38 but not JNK. The expression level of anti-apoptotic molecule, Bcl-X, was decreased by VCA treatment but not BV. Finally, the phosphorylation level of ERM proteins involved in the cytoskeleton homeostasis was decreased by both stimuli. Conclusion: We examined the involvement of kinase in VCA or BV - induced apoptosis by using kinase inhibitors. VCA-induced apoptosis was partially inhibited by in the presence.

• 대한한방부인과학회지
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• 제36권1호
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• pp.23-34
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• 2023

Objectives: This study was conducted to confirm the anticancer effect of Torilis Japonica (TJ) on cervical cancer and to determine whether the effect was apoptosis. Methods: In this study, the effect of TJ extract on toxicity, mitochondrial morphology, nuclear morphological changes, Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathway were investigated in HeLa cell, human cervical cancer cell. Results: The cytotoxicity, ratio of cells with nuclear changes to the total number of cells, and P38 phosphorylation increased in a concentration-dependent manner after administration of TJ extract. The length of mitochondria and ERK phosphorylation in HeLa cells decreased in a concentration-dependent manner after administration of TJ extract. Conclusions: TJ extract has an anticancer effect on cervical cancer cells, which is presumed to be due to apoptosis, and showed potential as a future cervical cancer treatment.

• Clinical and Experimental Reproductive Medicine
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• 제48권3호
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• pp.211-220
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• 2021

Objective: The present study aimed to investigate the possibility that curcumin (CMN) protects against methotrexate (MTX)-induced testicular damage by affecting the phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. Methods: Eighteen male Wistar albino rats were randomly divided into three groups. The control group was given an intragastric administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given intragastric CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single intraperitoneal dose of MTX (20 mg/kg) on the 11th day. At the end of the experiment, all animals were sacrificed and the testicular tissues were removed for morphometry, histology, and immunohistochemistry. Body and testicular weights were measured. Results: Body weights, seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. Whereas, the number of histologically damaged seminiferous tubules and interstitial space width significantly increased in the MTX group. In addition, the number of p-p38 MAPK immunopositive cells and the immunoreactivity of NF-κB also increased in the MTX group compared to the control group. CMN improved loss of body weight, morphometric values, and histological damage due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-κB immunoreactivity. Conclusion: CMN may reduce MTX-induced testicular damage by suppressing the p38 MAPK and NF-κB signaling pathways.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권3호
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• pp.227-237
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• 2007

Microglial cell activation is known to contribute to neuropathic pain following spinal sensory nerve injuries. In this study, I investigated its mechanisms in the case of trigeminal sensory nerve injuries by which microglial cell and p38 mitogen-activated protein kinase (p38 MAPK) activation in the medullary dorsal horn (MDH) would contribute to the facial pain hypersensitivity following mandibular nerve transection (MNT). And also investigated the changes of trigeminal ganglion neurons and ERK, p38 MAPK manifestations. Activation of microglial cells was monitored at 1, 3, 7, 14, 28 and 60 day using immunohistochemical analyses. Microglial cell activation was primarily observed in the superficial laminae of the MDH. Microglial cell activation was initiated at postoperative 1 day, maximal at 3 day, maintained until 14 day and gradually reduced and returned to the basal level by 60 days after MNT. Pain hypersensitivity was also initiated and attenuated almost in parallel with microglial cell activation pattern. To investigate the contribution of the microglial cell activation to the pain hypersensitivity, minocycline, an inhibitor of microglial cell activation by means of p38 MAPK inhibition, was administered. Minocycline dose-dependently attenuated the development of the pain hypersensitivity in parallel with inhibition of microglial cell and p38 MAPK activation following MNT. Mandibular nerve transection induced the activation of ERK, but did not p38 MAPK in the trigeminal ganglion. These results suggest that microglial cell activation in the MDH and p38 MAPK activation in the hyperactive microglial cells play an important role in the development of facial neuropathic pain following MNT. The results also suggest that ERK activation in the trigeminal ganglion contributes microglial cell activation and facial neuropathic pain.

• 한국응용과학기술학회지
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• 제30권1호
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• pp.173-182
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• 2013

아토피성 피부염은 만성 재발성 염증성 피부질환으로 피부장벽기능의 이상과 환경유발인자에 대한 피부과민성과 연관되어 있다. 이전의 연구에서는 아토피성피부염에 효과적인 약용식물 추출물을 발굴하기 위하여 노회, 자회지정, 석류, 석곡 추출물들의 세포독성, 항산화, 항염, 항알레르기 효과를 검토하였다. 본 연구에서는 지질다당류로 활성화시킨 대식세포 RAW26.7 에 대한 약용식물 추출물들의 항염작용을 보다 상세하게 검토하여 항염작용의 근본적인 분자기전을 확인하고자 하였다. 역전사중합효소연쇄반응분석(reverse transcription polymerase chain reaction analysis) 결과, 석류, 석곡, 노회는 염증성 사이토카인인 IL-6 와 IL-$1{\beta}$ 유전자발현을 현저하게 억제시켰으며 자화지정은 영향이 없었다. 형질주입과 발광효소분석(transfection and luciferase analysis) 결과, 약용식물 모두가 전사 핵인자 카파비(NF-${\kappa}B$)의 활성화를 억제시켰다. 웨스턴 블럿 분석(western blot analysis) 결과, 노회는 JNK MAP 인산화효소의 활성화를 차단하였지만 p38 MAP 인산화효소의 활성화는 차단하지 못하였다. 반면에 자화지정, 석류, 석곡은 JNK MAP 인산화효소뿐만 아니라 p38 MAP 인산화효소의 활성화도 차단하였다. 이들 실험결과들은 노회, 자화지정, 석류, 석곡은 항염효능을 가지고 있으며 따라서 아토피성 피부염의 증상을 경감 또는 완화시키는 잠재력이 있음을 보여 준다.

• Korean Journal of Acupuncture
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• 제31권1호
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• pp.14-19
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• 2014

목적 : 본 연구에서는 정향 에탄올 추출물이 RBL-2H3 세포 매개 알레르기 반응에 대해 미치는 영향과 그 작용기전에 대해 연구했다. 방법 : 정향 에탄올 추출물의 RBL-2H3 세포에 대한 독성 여부는 MTT 분석을 통해 평가했다. 정향 에탄올 추출물의 항알러지 작용은 효소결합면역 분석방법(ELISA)을 이용해 ${\beta}$-Hexosaminidase과 Histamine의 분비량을 측정하여 평가하였다. 정향 에탄올 추출물의 작용기전에 대해서는 유사 분열물질-활성화단백질인산화효소(mitogen-activated protein kinase, MAPK)를 western blot 법을 이용하여 측정함으로써 평가하였다. 결과 : 정향의 에탄올 추출물은 RBL-2H3 세포에 대해 독성을 나타내지 않는 농도에서 RBL-2H3 세포의 탈과립과 히스타민 분비를 유의하게 억제하였으며, p38 MAPK의 활성을 차단하였다. 결론 : 본 연구의 결과 정향의 에탄올 추출물은 비만세포에서 유래된 알러지 반응을 억제하는 효과가 있으며, 또한 그 작용기전은 p38 MAPK 인산화와 연계되어 있을 것으로 사료된다.

• 한방안이비인후피부과학회지
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• 제25권3호
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• pp.1-12
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• 2012

Objectives : Fagopyrum esculentum(FE) has been used for removal of inflammation of internal organs and treatment of sore and ulcer by heat toxin in Korean herbal medicines. In this study, To investigated the protective effect of FE on allergic response, we determined whether FE inhibits allergic response. Methods : The effect of FE was analyzed by ELISA, RT-PCR and Western blot in RBL-2H3 cells. We investigated cell viability, ${\beta}$-hexosaminidase, as a marker of degranulation, cytokne, and intracellular ROS and MAPK and NF-${\kappa}B$ signaling. Results : We found that FE suppressed ${\beta}$-hexosaminidase release, the production of IL-4 and TNF-${\alpha}$ and intracellular ROS level in RBL-2H3 by the anti-DNP IgE plus DNP-HSA stimulation. FE also significantly inhibited cytokine mRNA expressions, such as IL-$1{\beta}$, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF in RBL-2H3. In addition, PF suppressed the phospholyation of ERK1/2, JNK1/2, p38 and $I{\kappa}B{\alpha}$ and NF-${\kappa}B$ signal transduction pathway. Conclusions : Our results indicate that FE protects against allergic response and exerts an anti-inflammatory effect through the inhibition of degranulation and production of cytokines and ROS via the suppression MAPK and NF-${\kappa}B$ of signal transduction. Abbrevations : FE, Fagopyrum esculentum; RBL-2H3, rat basophilic leukemia cell line; ROS, reactive oxygen species; MAPK, Mitogen-activated protein kinase; $NF{\kappa}B$, nuclear factor ${\kappa}B$; $TNF{\alpha}$, Tumor necrosis factor alpha; GM-CSF, Granulocyte macrophage colony-stimulating factor; ERK, extracellular-signal-regulated kinase; JNK, c-Jun NH2-terminal kinase; p38, p38 MAP kinase; $I{\kappa}B{\alpha}$, inhibitory-kappa B alpha.

• Toxicological Research
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• 제17권
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• pp.89-96
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• 2001

Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.