• Korean Journal of Acupuncture
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• v.32 no.3
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• pp.116-123
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• 2015

Objectives : The present study was designed to investigate effects and molecular mechanisms of Atractylodes macrocephala Koidzumi extracts(AMK) on the improvement of adipocyte dysfunction induced by TNF-${\alpha}$ in 3T3-L1 adipocytes. We examined whether AMK could directly influence the inflammation and insulin resistance in 3T3-L1 adipocytes. Methods : Potential roles of AMK in the lipolysis, production of inflammatory adipokines and ROS, expression and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, and expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ were investigated in this study. Results : Our data demonstrated that TNF-${\alpha}$ significantly increased lipolysis, levels of MCP-1, IL-6, and ROS and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, while TNF-${\alpha}$ reduced the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ in adipocytes, suggesting that TNF-${\alpha}$ induced a condition with the occurrence of inflammation and insulin resistance. Those alterations induced by TNF-${\alpha}$ were prevented by the treatment of AMK. AMK down-regulated the phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein and up-regulated the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ on TNF-${\alpha}$-induced inflammation and insulin resistance. Conclusions : Thus, our results indicate that AMK can be used to prevent from the TNF-${\alpha}$-induced adipocyte dysfunction through MAPK, $NF{\kappa}B$ and $PPAR{\gamma}$ pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.519-526
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• 2012

Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. It is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.

• Journal of Nutrition and Health
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• v.35 no.1
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• pp.53-59
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• 2002

Green tea has been recognized as a favorite beverage for centuries in Easter and Westers cultures. Recently, anti-tumor effects of green tea constituents have received increasing attention. However, the mechanism of catechin-mediated cytotoxicity against tumor cells remains to be elusive. To elucidate the mechanical insights of anti-tumor effects, (-)epigallocatechin-gallate(EGCG) of catechin was applied to human lung cancer A549 cells. (-)EGCG induced the death of A549 cells, which was revealed as apoptosis in DNA fragmentation assay. (-)EGCG induced the activation of caspase family cysteine proteases including capase-3, -8 and -9 proteases in A549 cells. Furthermore, (-)EGCG increased the phosphotransferase activity of c-Jun N-terminal kinase 1JNK 1), which further induced tole transcriptional activation of activating protein-1(AP-1) in A549 cells. We suggest that (-)EGCG-induced apotosis of A549 cells is mediated by signaling pathway involving caspase family cysteine protease, JNK1 and transcription factor, AP-1.

• Journal of the Korean Wood Science and Technology
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• v.42 no.5
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• pp.523-532
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• 2014

This study was done to evaluate the antioxidant effect of oak hot water extracts on the oxidative stress induced by reactive oxygen species (ROS). The cytotoxicity of $H_2O_2$-induced oxidative stress was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for the cell viability according to the dose-dependent treatment. Oak extracts demonstrated a dose-dependent ability to inhibit $H_2O_2$-induced apoptosis in cultured tenofibroblasts, as assessed by MTT assay and FACS analysis. $H_2O_2$ increased the phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and of c-Jun N-terminal kinase (JNK) and the production of reactive oxygen species (ROS). In contrast, treatment with oak extracts was decreased this activation of ERK1/2 and JNK, as confirmed by western blot analysis, and reduced the production of ROS, as verified by fluorescent microscopic and flow cytometry (FACS) analyses. These findings suggest that oak extracts, by suppressing JNK, ERK1/2, and intracellular ROS production, have a concentration-dependent antiapoptotic effect on achilles tenofibroblasts exposed to an oxidative stressor, and may have therapeutic potential.

• Korean Journal of Pharmacognosy
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• v.41 no.3
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• pp.190-195
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• 2010

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. NNMBS098, a composition comprising the water insoluble of the 70% EtOH extract of Zingiberis Rhizoma, showed the potent neuroprotective effects on glutamateinduced neurotoxicity by induced the expression of heme oxygenase (HO)-1 and increased HO activity in the mouse hippocampal HT22 cells. Furthermore, NNMBS098 caused the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in mouse hippocampal HT22 cells. In addition, we found that treatment with c-Jun N-terminal kinase (JNK) inhibitor (SP600125) reduced NNMBS098-induced HO-1 expression and NNMBS098 also increased JNK phosphorylation. Therefore, these results suggest that NNMBS098 increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through JNK pathway-Nrf2-dependent HO-1 expression.

• BMB Reports
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• v.44 no.9
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• pp.601-606
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• 2011

HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML.

• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.216-221
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• 2013

Aromadendrin, a flavonol, has been reported to possess a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-diabetic properties. However, the underlying mechanism by which aromadendrin exerts its biological activity has not been extensively demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of aromadedrin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Aromadendrin significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$. In accordance, aromadendrin attenuated LPS-induced overexpression iNOS and COX-2. In addition, aromadendrin significantly suppressed LPS-induced degradation of $I{\kappa}B$, which sequesters NF-${\kappa}B$ in cytoplasm, consequently inhibiting the nuclear translocation of pro-inflammatory transcription factor NF-${\kappa}B$. To elucidate the underlying signaling mechanism of anti-inflammatory activity of aromadendrin, MAPK signaling pathway was examined. Aromadendrin significantly attenuated LPS-induced activation of JNK, but not ERK and p38, in a concentration-dependent manner. Taken together, the present study clearly demonstrates that aromadendrin exhibits anti-inflammatory activity through the suppression of nuclear translocation of NF-${\kappa}B$ and phosphorylation of JNK in LPS-stimulated RAW 264.7 macrophage cells.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.784-790
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• 2005

In this study, we evaluate the effects of (-)-epigallocatechin-3-gallate (EGCG) on ultraviolet B(UVB)-irradiated living skin equivalents (LSEs). Histologically, UVB irradiation induced thinning of the LSE epidermis, whereas EGCG treatment led to thickening of the epidermis. Moreover, EGCG treatment protected LSEs against damage and breakdown caused by UVB exposure. Immunohistochemically, UVB-exposed LSEs expressed p53, Fas, and 8-hydroxy-deoxyguanosine (8-OHdG), all of which are associated with apoptosis. However, EGCG treatment reduced the levels of UVB-induced apoptotic markers in the LSEs. In order to determine the signaling pathways induced by UVB, Western blot analysis was performed for both c-Jun $NH_2$-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), which are associated with UVB-induced oxidative stress. UVB activated JNK in the epidermis and dermis of the LSEs, and EGCG treatment reduced the UVB-induced phosphorylation of JNK. In addition, p38 MAPK was also found to have increased in the UVB-exposed LSEs. Also, EGCG reduced levels of the phosphorylation of UVB-induced p38 MAPK. In conclusion, pretreatment with EGCG protects against UVB irradiation via the suppression of JNK and p38 MAPK activation. Our results suggest that EGCG may be useful in the prevention of UVB-induced human skin damage, and LSEs may constitute a potential substitute for animal and human studies.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.413-422
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• 2020

Delphinidin is a major anthocyanidin compound found in various vegetables and fruits. It has anti-oxidant, anti-inflammatory, and various other biological activities. In this study we demonstrated the anti-cancer activity of delphinidin, which was related to autophagy, in radiation-exposed non-small cell lung cancer (NSCLC). Radiosensitising effects were assessed in vitro by treating cells with a subcytotoxic dose of delphinidin (5 μM) before exposure to γ-ionising radiation (IR). We found that treatment with delphinidin or IR induced NSCLC cell death in vitro; however the combination of delphinidin pre-treatment and IR was more effective than either agent alone, yielding a radiation enhancement ratio of 1.54 at the 50% lethal dose. Moreover, combined treatment with delphinidin and IR, enhanced apoptotic cell death, suppressed the mTOR pathway, and activated the JNK/MAPK pathway. Delphinidin inhibited the phosphorylation of PI3K, AKT, and mTOR, and increased the expression of autophagy-induced cell death associated-protein in radiation-exposed NSCLC cells. In addition, JNK phosphorylation was upregulated by delphinidin pre-treatment in radiation-exposed NSCLC cells. Collectively, these results show that delphinidin acts as a radiation-sensitizing agent through autophagy induction and JNK/MAPK pathway activation, thus enhancing apoptotic cell death in NSCLC cells.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.207-216
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• 2021

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4℃) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tail-flick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.