• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.415-424
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• 2016

Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.337-343
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• 2017

Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells. Kahweol increased apoptosis in human colorectal cancer cells. It also increased ATF3 expression through the transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by kahweol was CREB located between -147 to -85 of ATF3 promoter. ATF3 overexpression increased kahweol-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by kahweol. Inhibition of ERK1/2 and $GSK3{\beta}$ blocked kahweol-mediated ATF3 expression. The results suggest that kahweol induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

• International Journal of Oral Biology
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• v.44 no.1
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• pp.20-26
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• 2019

Periodontal diseases have been associated with the development of cardiovascular diseases. Accumulating evidences have indicated that Porphyromonas gingivalis, a major periodontopathic pathogen, plays a critical role in the pathogenesis of atherosclerosis. In the present study, we demonstrated that P. gingivalis lipopolysaccharide (LPS) increases the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9) in rat vascular smooth muscle cells. We showed that the MMP-9 expression induced by P. gingivalis LPS is mediated by the activation of signal transducer and activator of transcription 3 (STAT3) in vascular smooth muscle cells. Furthermore, the inhibition of STAT3 activity reduced P. gingivalis LPS-induced migration of vascular smooth muscle cells. Overall, our findings indicate that P. gingivalis LPS stimulates the migration of vascular smooth muscle cells via STAT3-mediated MMP-9 expression.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.113-123
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• 2022

Diarylpropionitrile (DPN), a selective agonist for estrogen receptor β (ERβ), has been reported to regulate various hormonal responses through activation of ERβ in tissues including the mammary gland and brain. However, the effect of DPN on melanogenesis independent of ERβ has not been studied. The aim of this study is to examine the possibility of anti-melanogenic effect of DPN and its underlying mechanism. Melanin contents and cellular tyrosinase activity assay indicated that DPN inhibited melanin biosynthesis in alpha-melanocyte stimulating hormone-stimulated B16F10 melanoma cell line. However, DPN had no direct influence on in vitro tyrosinase catalytic activity. On the other hand, 17β-estradiol had no effect on inhibition of melanogenesis, suggesting that the DPN-mediated suppression of melanin production was not related with estrogen signaling pathway. Immunoblotting analysis showed that DPN down-regulated the expression of microphthalmia-associated transcription factor (MITF), a central transcription factor of melanogenesis and its down-stream genes including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Also, DPN attenuated the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Additionally, DPN suppressed the melanin synthesis in UVB-irradiated HaCaT conditioned media culture system suggesting that DPN has potential as an anti-melanogenic activity in physiological conditions. Collectively, our data show that DPN inhibits melanogenesis via downregulation of PKA/CREB/MITF signaling pathway.

• Food Science and Biotechnology
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• v.18 no.6
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• pp.1371-1378
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• 2009

The aim of this study is to elucidate the anti-inflammatory activities of chopi (Zanthoxylum piperitum A.P. DC.) essential oil. Essential oil (EO) of chopi was extracted by steam distillation method, and its major constituents were limonene and geranyl acetate. Chopi-EO decreased approximately 38% of nitrite production, as compared to the lipopolysaccharde (LPS)-induced nitrite production. However, chopi-EO and its components did not quench nitric oxide (NO) chemically in cellfree system, and markedly inhibited approximately 40.4% of inducible nitric oxide synthase (iNOS) mRNA transcription. In addition, the inhibition of E-selectin gene transcription by chopi-EO caused the suppression of cellular adhesion. These results suggest that chopi-EO may exert potential anti-immunological inflammatory activity.

• Korean Journal of Plant Resources
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• v.29 no.3
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• pp.281-288
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• 2016

Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.

• Bulletin of the Korean Chemical Society
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• v.20 no.8
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• pp.925-928
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• 1999

The process of transcription is the major point at which gene expression is regulated. The jun and fos families of eukaryotic transcription factor heterodimerize to form complexes capable of binding 5'-TGAGTCA-3'DNA elements (AP-1 binding site). To search for the inhibitors of the jun-fos-DNA complex formation, several natural products extracts were screened and methanol extract of tanshen (the dried roots of Salvia miltiorrhiza Bunge) showed remarkable inhibitory activity. The active compounds of the extracts were purified using re-peated column chromatography and recrystallization. Their structures were identified as tanshinone I and tanshinone IIA. Through the electrophoresis mobility shift assay and cell cytotoxicity test, tanshinone I and tanshinone IIA were identified as inhibitors that suppress not only AP-1 function but also the cell proliferation. Tanshinone I also suppressed the jun-fos-DNA complex formation in TPA-induced NIH 3T3 cells.

• Journal of Life Science
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• v.25 no.10
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• pp.1115-1123
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• 2015

The purpose of this study was to investigate the potential of Nelumbo nucifera G. leaf (NNL) extract as a cosmetic additive. The electron-donating ability of the NNL extract at a concentration of 1,000 μg/ml was 67.83%. In xanthine oxidase, the inhibition effect of the NNL extract was 92.7% at the same concentration. For whitening effects, tyrosinase inhibition effect of NNL extract was 42.7% at a 1,000 μg/ml concentration. The cell toxicity of the NNL extract was examined in melanoma cells (B16F10) using a 3-[4, 5–dimethyl–thiazol–2–yl]-2, 5-diphenyl-tetrazoliumbromide (MTT) assay. The cell toxicity assay revealed that the NNL extract had a toxicity of 81.61% at a concentration of 1,000 μg/ml The microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), tyrosinase related protein-2 (TRP-2), and tyrosinase protein expression inhibitory effect by Western blot of NNL extract were measured by a Western blot at concentrations of 25, 50, and 100 μg/ml. At a 100 μg/ml concentration of the NNL extract, the expression of the MITF, TRP-1, TRP-2, and tyrosinase protein was decreased by 69.59%, 27.74%, 67.33%, and 67.78% respectively. The MITF, TRP-1, TRP-2 and tyrosinase mRNA expression inhibitory effect were measured by reverse transcription- polymerase chain reaction (PCR) at concentrations of 25, 50, and 100 μg/ml. GAPDH was used as a positive control. At a concentration of 100 μg/ml of the NNL extract, the expression of MITF, TRP-1, TRP-2, and tyrosinase mRNA was decreased by 67.51%, 71.36%, 85.74%, and 83.64%, respectively. These findings suggest that the NNL extract has antioxidant and whitening effects and that it has great potential as a cosmetic ingredient.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.1
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• pp.1-7
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• 2013

Samjunghwan (SJH) was fermented using five different probiotic bacterial strains (Lactobacillus plantarum, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillus acidophilus or Bifidobacterium longum) separately. We examined the inhibition of preadipocyte differentiation through Oil Red O staining and analyzed the expression of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EPB{\alpha}$), peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), uncoupling protein (UCP)-2, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which are adipogenic transcription factors. Both Lactobacillus plantarum and Enterococcus faecium-fermented SJH reduced Oil Red O dye staining compared with the same dose of non-fermented SJH. Only Lactobacillus plantarum-fermented SJH inhibited all adipogenic transcription factors and showed the best down-regulation of $PPAR{\gamma}$, UCP-2, and HMG-CoA reductase compared with the same dose of non-fermented SJH. The effect of SJH on the inhibition of preadipocyte differentiation was more prominent from the fermented SJH. Lactobacillus plantarum-fermented SJH, in particular, blocks the expression of $PPAR{\gamma}$, UCP-2, HMG-CoA reductase.

• Journal of Nutrition and Health
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• v.47 no.3
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• pp.167-175
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• 2014

Purpose: Previous studies have shown that treatment with Smilax china L. leaf extract (SCLE) produces antidiabetic effects due to ${\alpha}$-glucosidase inhibition. In this study, we examined the mechanism underlying these antidiabetic effects by examining glucose uptake in HepG2 cells cultured with SCLE. Methods: Glucose uptake and glucokinase activity were examined using an assay kit. Expression of glucose transporter (GLUT)-2, GLUT-4, and HNF-$1{\alpha}$ was measured by RT-PCR or western blot. Results: Treatment with SCLE resulted in enhanced glucose uptake in HepG2 cells, and this effect was especially pronounced when cells were cultured in an insulin-free medium. SCLE induced an increase in expression of GLUT-2 but not GLUT-4. The increase in the levels of HNF-$1{\alpha}$, a GLUT-2 transcription factor, in total protein extract and nuclear fraction suggest that the effects of SCLE may occur at the level of GLUT-2 transcription. In addition, by measuring the change in glucokinase activity following SCLE treatment, we confirmed that SCLE stimulates glucose utilization by direct activation of this enzyme. Conclusion: These results demonstrate that the potential antidiabetic activity of SCLE is due at least in part to stimulation of glucose uptake and an increase in glucokinase activity, and that SCLE-stimulated glucose uptake is mediated through enhancement of GLUT-2 expression by inducing expression of its transcription factor, HNF-$1{\alpha}$.