• 한국자원식물학회지
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• 제36권3호
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• pp.191-197
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• 2023

Autophagy contributes to enhancing the immune system (innate and adaptive immune system) against foreign pathogens. Autophagy of macrophages is used as a major indicator for developing vaccine adjuvants to increase the adaptive immune response. In this study, HSL increased p62/SQSTM1 expression. Inhibition of TLR4, p38, JNK, and NF-κB blocked HSL-mediated increase of p62/SQSTM1. HSL activated p38, JNK, and NF-κB signaling, but HSL-mediated activation of p38, JNK, and NF-κB signaling was reversed by TLR4 inhibition. In addition, HSL increased Nrf2 expression, but HSL-mediated Nrf2 expression did not occur in the inhibition of TLR4, p38, JNK, and NF-κB. Taken together, it is believed that HSL-mediated autophagy may be dependent on activating Nrf2 expression via TLR4-dependent activation of p38, JNK, and NF-κB in macrophages.

• 통합자연과학논문집
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• 제15권4호
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• pp.145-152
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• 2022

Colon rectal cancer is one of the frequently diagnosed cancers worldwide. In recent times the drug discovery for colon cancer is challenging because of their speedy metastasis and morality of these patients. C-jun N-terminal kinase signaling pathway controls the cell cycle survival and apoptosis. Evidence has shown that JNK1 promotes the tumor progression in various types of cancers like colon cancer, breast cancer and lung cancer. Recent study has shown that inhibiting, JNK1 pathway is identified as one of the important cascades in drug discovery. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened ChEMBL dataset against JNK1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top compounds to be more specific with JNK1 comparing the affinity with JNK2 and JNK3.The drugs which exhibited higher binding were subjected to Conceptual - Density functional theory. The results showed mainly Entrectinib and Exatecan showed better binding to the target.

• 한방안이비인후피부과학회지
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• 제29권2호
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• pp.56-64
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• 2016

Objectives : The purpose of this study is to observe the effects of Gardeniae Fuctus(GF) on the metabolic process of antioxidant and anti-inflammation. Methods : 4-HNE was injected into PC-12 cell to cause oxidative stress-induced inflammatory response, and then a western blot was conducted to observe the expression of Nuclear Factor-kB (NF-kB) and c-Jun N-terminal kinase (JNK) protein that are important factors involved with inflammation. Results : 1. The Gardeniae Fuctus water extract 50 ㎍ and 100 ㎍ significantly suppressed the increase in JNK protein expression in PC-12 cell. 2. The Gardeniae Fuctus water extract 50 ㎍, 100 ㎍ and 200 ㎍ significantly suppressed the increase in NF-kB protein expression in PC-12 cell. Conclusion : These results suggest that the Gardeniae Fuctus water extract has antioxidative and anti-inflammatory activity through suppressing the activity of JNK and NF-kB.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.165.3-166
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• 2003

The c-Jun N-terminal kinase (JNK) plays essential roles in apoptosis and cell survival. Because apoptosis is promoted by blocking the MEK kinase1-mediated activation of JNK1, we tested whether JNK1 plays dual roles in apoptosis. We show here that JNK1 activity is differentially up-regulated in a two-tiered fashion by specific mechanisms during taxol- or ginsenoside Rh2-induced apoptosis. The early phase of JNK1 activation, but not apoptosis is prevented by expressing the dominant negative SEK1 mutant. (omitted)

• 통합자연과학논문집
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• 제5권1호
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• pp.6-12
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• 2012

c-Jun N-terminal kinase-3 (JNK-3) has been identified as a promising target for neuronal apoptosis and has the effective therapeutic for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. Herein, we report the essential structural and chemical parameters for JNK-3 inhibitors utilizing comparative molecular field similarity indices analysis (CoMSIA) using the derivatives of 3,5-disubstituted quinolines. The best predictions were obtained CoMSIA model (q2=0.834, r2=0.987) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.

• 동의생리병리학회지
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• 제21권1호
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• pp.76-81
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• 2007

The effect of either low or high intensity four weeks exercise treadmill running on the activation of the extracellular-signal regulated protein kinase (ERK1/2) and the c-Jun N-terminal kinase(JNK) pathways was determined in rat tibialis muscle. Sprague-Dawley rats were assigned to one of three groups: (i) sedentary group(NE; n=10); (ii) low intensity exercise group (8m/min; LIE; n=10); and (iii) high intensity exercise group(28m/min; HIE; n=10). The training regimens were planned so that animals covered the same distance and had similar glycogenutilization for both LIE and HIE exercise sessions. After four weeks exercise, 48 h after the last exercise bout obtained samples. pERK1 increased 1.5 times comparing with the sedentary group in the low intensity group while it increased 11.7 times in high intensity group, in the tibialis of rats. In the low intensity group, pERK2 increased 1.4 times comparing with the sedentary group while it increased 3.3 times in high intensity group. While pJNK1 decreased 0.9 times, comparing with the sedentary group, pJNK2 was increased to 0.5 times in the low intensity group. But in high intensity group, pJNK2 decreased 0.7 times while pJNK1 didn't show any change. In conclusion, Four weeks exercise of different intensities results in tibialis muscle activation of intracellular signal pathways, which may be one mechanism regulating specific adaptations induced by different exercise intensities.

• 통합자연과학논문집
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• 제7권1호
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• pp.45-49
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• 2014

The (c-Jun N-terminal kinase 3) JNK3 is a potential therapeutic target for various neurological disorders. Here, a three dimensional quantitative structure-activity relationship (3D-QSAR) study on phenoxypyridine as JNK3 inhibitors was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The comparative molecular field analysis (CoMFA) using different partial atomic charges, was employed to understand the structural factors affecting JNK3 inhibitory potency. The Gasteiger-Marsili yielded a CoMFA model with cross-validated correlation coefficient ($q^2$) of 0.54 and non-cross-validated correlation coefficient ($r^2$) of 0.93 with five components. Furthermore, contour maps suggested that bulky substitution with oxygen atom in $R^3$ position could enhance the activity considerably. The work suggests that further chemical modifications of the compounds could lead to enhanced activity and could assist in the design of novel JNK3 inhibitors.

• Molecules and Cells
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• 제41권5호
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• pp.401-412
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• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• Biomolecules & Therapeutics
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• 제28권1호
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• pp.104-109
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• 2020

Probenecid is a representative drug used in the treatment of gout. A recent study showed that probenecid effectively inhibits oxidative stress in neural cells. In the present study, we investigated whether probenecid can affect osteoclast formation through the inhibition of reactive oxygen species (ROS) formation in RAW264.7 cells. Lipopolysaccharide (LPS)-induced ROS levels were dose-dependently reduced by probenecid. Fluorescence microscopy analysis clearly showed that probenecid inhibits the generation of ROS. Western blot analysis indicated that probenecid affects two downstream signaling molecules of ROS, cyclooxygenase 2 (COX-2) and c-Jun N-terminal kinase (JNK). These results indicate that probenecid inhibits ROS generation and exerts antiosteoclastogenic activity by inhibiting the COX-2 and JNK pathways. These results suggest that probenecid could potentially be used as a therapeutic agent to prevent bone resorption.

• 생명과학회지
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• 제19권8호
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• pp.1119-1124
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• 2009

포화 지방산이 인슐린 저항성 및 지방간등의 다양한 질병의 발병에 관련된다고 보고되고 있다. 그러나 간세포에서 포화지방산이 세포 사멸에 대한 효과 및 이와 관련된 신호전달계에 대해서는 거의 알려져 있지 않고 있다. 본 연구에서는 대표적인 포화지방산인 palmitic acid 처리 시 랫트 간세포 사멸에 미치는 효과와 이들이 mitogen activated protein kinases (MAPKs)와 관련되는 지를 알아보았다. 본 실험에서 palmitic acid 처리 시 간세포 성장은 억제 되었고 lactate dehydrogenase (LDH) 활성은 증가하였다. 이러한 작용은 JNK 및 p38 MAPK 억제제에 의해서 선택적으로 차단되었다. 아울러 palmitic acid에 의한 Bcl-2 발현 억제, Bax 발현 증가 작용, GSH 함량 감소작용 및 산화성 스트레스 증가작용 역시 JNK 및 p38 MAPK 억제제에 의해서 선택적으로 차단되었다. 실제로 palmitic acid 처리시 JNK 및 p38 MAPK 활성은 증가하였다. 결론적으로 palmitic acid는 간세포에서 JNK 및 p38 MAPK 활성을 경유하여 산화성 스트레스 증가를 통하여 간세포 사멸을 유도하는 것으로 나타났다.