• Advances in Traditional Medicine
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• v.9 no.4
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• pp.285-291
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• 2009

Cadmium ($Cd^{2+}$) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. However, the auditory effect of $Cd^{2+}$ is not poorly understood. The purpose of the present study was to investigate whether prevent the ototoxic effects of $Cd^{2+}$ by antioxidnat in auditory cell line, HEI-OC1. Rosmarinic acid is a naturally occurring phenolic compound and also known to possess marked antioxidant properties. We showed that antioxidnat inhibited the the cytochrome c release induced by $Cd^{2+}$. In addition, we showed that the regulatory effect of antioxidnat on apoptosis is through the caspase-9 activation, and extracellular signal-regulated kinase activation in auditory cells. These results suggested antioxidnat its therapeutic usefulness, against $Cd^{2+}$ induced activation of caspase-9 and ERK.

• Natural Product Sciences
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• v.13 no.2
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• pp.169-173
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• 2007

Luteolin is a major flavonoid of Lonicera japonica and has anti-inflammatory effect. The activation of proteinase-activated receptor (PAR)-2 and -4 by trypsin appears to play a role in inflammation, In the present study, we examined the inhibitory effects of luteolin on activation of trypsin-induced human leukemic mast cells (HMC-1). HMC-1 cells were stimulated with trypsin, PAR-2 and PAR-4 agonist, in the presence or absence of luteolin. The level of TNF-${\alpha}$ secretion was measured by enzyme-linked immunosorbent assay (ELISA). The expression of tryptase and phosphorylated-extracellular signal-regulated kinase (ERK) were assessed by Westem blot analysis. Moreover, trypsin activity was measured by the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). TNF-${\alpha}$ secretion and Tryptase expression in trypsin-stimulated HMC-1 cells were markedly inhibited by pretreatment of luteolin. Furthermore, the pretreatment of luteolin resulted in the reduction of ERK phosphorylation and trypsin activity. These results suggest that luteolin might has the inhibitory effects on the PAR-2 and -4-dependent inflammation.

• Toxicological Research
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• v.35 no.3
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• pp.279-285
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• 2019

In this study, we investigated the therapeutic potential of Cinnamomum camphora leaves on allergic skin inflammation such as atopic dermatitis. We evaluated the effects of C. camphora leaves on human adult low-calcium high-temperature keratinocytes and atopic dermatitis mice. C. camphora leaves inhibited Macrophage-derived chemokine (an inflammatory chemokine) production in $interferon-{\gamma}$ (10 ng/mL) stimulated Human adult low-calcium high-temperature keratinocytes in a dose dependent manner. C. camphora leaves suppressed the phosphorylation of janus kinase signal transducer and activator of transcription 1. C. camphora leaves also suppressed the phosphorylation of extracellular signal-regulated kinase 1/2, a central signaling molecule in the inflammation process. These results suggest that C. camphora leaves exhibits anti-inflammatory effect via the phosphorylation of signal transducer and activator of transcription 1 and extracellular signal-regulated kinase 1/2. To study the advanced effects of C. camphora leaves on atopic dermatitis, we induced experimental atopic dermatitis in mice by applying 2,4-dinitrochlorobenzene. The group treated with C. camphora leaves (100 mg/kg) showed remarkable improvement of atopic dermatitis symptoms: reduced serum immunoglobulin E levels, smaller lymph nodes with reduced thickness and length, decreased ear edema, and reduced levels of inflammatory cell infiltration in the ears. Interestingly, the effects of C. camphora leaves on atopic dermatitis symptoms were stronger than those of hydrocort cream, a positive control. Taken together, C. camphora leaves showed alleviating effects on the inflammatory chemokine production in vitro and atopic dermatitis symptoms in vivo. These results suggest that C. camphora leaves help in the treatment of allergic inflammation such as atopic dermatitis.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.73-78
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• 2008

Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), has been shown to have a variety of biological functions such as immunostimulating and anti-tumor activities. In the present study, we investigated whether RGAP inhibited ligand-induced platelet aggregation. The washed platelet-rich plasma was prepared from male SD rats with successive centrifugation. The platelets $(10^8/ml)$ were preincubated with 1 mM of $CaCl_2$ for 2 min either in the presence or in the absence of RGAP $(10{\sim}50\;{\mu}g/ml)$ and were stimulated with collagen (2.5 ${\mu}g/ml$) and thrombin (0.1 U/ml). RGAP dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of $26.2{\pm}2.0$ ${\mu}g/ml$. In collagen-induced platelet aggregation, RGAP inhibited the reaction with an $IC_{50}$ value of $31.5{\pm}3.0\;{\mu}g/ml$. RGAP potently suppressed the intracellular calcium ion, which was stimulated by thrombin (0.1 U/ ml). Among mitogen-activated protein kinase (MAPK) subtypes, the extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK were analyzed in the present study. RGAP inhibited the phosphorylation of ERK2 and p38 MAPK, which was activated by collagen (2.5 ${\mu}g/ml$). Finally, these results suggested that besides saponin fraction, RGAP take an important role in the preventive effect of Korean red ginseng against cardiovascular disease such as thrombosis and atherosclerosis.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.90-97
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• 2021

Ultraviolet B (UVB) radiation causes DNA base modifications. One of these changes leads to the generation of 8-oxoguanine (8-oxoG) due to oxidative stress. In human skin, this modification may induce sunburn, inflammation, and aging and may ultimately result in cancer. We investigated whether phloroglucinol (1,3,5-trihydroxybenzene), by enhancing the expression and activity of 8-oxoG DNA glycosylase 1 (Ogg1), had an effect on the capacity of UVB-exposed human HaCaT keratinocytes to repair oxidative DNA damage. Here, the effects of phloroglucinol were investigated using a luciferase activity assay, reverse transcription-polymerase chain reactions, western blot analysis, and a chromatin immunoprecipitation assay. Phloroglucinol restored Ogg1 activity and decreased the formation of 8-oxoG in UVB-exposed cells. Moreover, phloroglucinol increased Ogg1 transcription and protein expression, counteracting the UVB-induced reduction in Ogg1 levels. Phloroglucinol also enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as Nrf2 binding to an antioxidant response element located in the Ogg1 gene promoter. UVB exposure inhibited the phosphorylation of protein kinase B (PKB or Akt) and extracellular signal-regulated kinase (Erk), two major enzymes involved in cell protection against oxidative stress, regulating the activity of Nrf2. Akt and Erk phosphorylation was restored by phloroglucinol in the UVB-exposed keratinocytes. These results indicated that phloroglucinol attenuated UVB-induced 8-oxoG formation in keratinocytes via an Akt/Erk-dependent, Nrf2/Ogg1-mediated signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6391-6395
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• 2014

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.2
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• pp.104-117
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• 2009

Objective : Melanin is one of the most important facor in skin color. Melanin protects human skin from ultraviolet radiation otherwise it causes melanin pigmentation. So this experiment is carried out for test whether Scutellaria baicalensis Georgi(SBG) inhibits melanin synthesis and tyrosinase activity in mouse B16 melanoma cells. Method : The melanin synthesis inhibition effects of SBG were examined by in vitro melanin production assay. We assessed inhibitory effects of SBG on melanin contents from B16F1 melanoma cell, on tyrosinase activity(cell and cell free system), effect of SBG on the expression tyrosinase, Microphthalmia-associated Transcription Factor(MITF), Extracellular signal-regulated Kinase(ERK). Result : SBG inhibited melanin synthesis induced $\alpha$-MSH($\alpha$-Melanin Stimulating Hormone) in B16F1. SBG inhibited tyrosinase activity and expression. And SBG down-regulates MITF and stimulated ERK activation in B16F1. Conclusion : According to above results, SBG was improved its suppression effect to the inhibition of melanin synthesis, tyrosinase activation, and tyrosinase promotor activation. So SBG is considered to be used for an strong source of skin whitening effect.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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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.

• Animal cells and systems
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• v.13 no.4
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• pp.363-370
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• 2009

Since vitamin $D_3$ is an important regulator of osteoblastic differentiation, a presently-established vitamin $D_3$-entrapped calcium phosphate film (VCPF) was evaluated for hard tissue engineering. The entrapped vitamin $D_3$ more rapidly induced bone nodule formation. To characterize the cellular events leading to regulations including faster differentiation, signal transduction pathways were investigated in osteoblastic MG63 cells at a molecular level. Major signaling pathways for MG63 cell proliferation including phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase and focal adhesion kinase pathways were markedly down-regulated when cells were cultured on calcium phosphate film (CPF) and VCPF. This agreed with our earlier observations of the immediate delay in proliferation of MG63 cells upon culture on CPF and VCPF. On the other hand, the p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase A (PKA) pathways were significantly up-regulated on both CPF and VCPF. CPF alone could simulate differential behaviors of MG63 cells even in the absence of osteogenic stimulation and entrapment of vitamin $D_3$ within CPF further amplified the signal pathways, resulting in continued promotion of MG63 cell differentiation. Interplay of p38 MAPK and PKA signaling pathways likely is a significant event for the promotion of differentiation and mineralization of MG63 cells.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.28 no.1
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• pp.31-41
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• 2002

The production of matrix matalloproteinases(MMPs) by the UV irradiated skin fibroblast and the degradation of extracellular matrix(ECM) by these enzymes is known as one of the main reasons of photoaging. Recently, Fisher group showed that the MMP expression is mainly regulated by the mitogen-activated protein(MAP) kinas family, such as extracellular signal-regulated kinase(ERK), c-Jun amino-terminal kinase(JNK) and p38, each of which forms a signaling pathway. In this work we first examined the effect of nitric oxide (NO) on the production of MMP-1 and MMP-2 by the human dermal fibroblasts (HDFs). NO is a multifunctional messenger molecule generated from L-arginine and involved in many kinds of signaling pathway. We found that the treatment of HDF with NO donor, sodium nitroprusside (SNP) enhanced the expression of MMPs with or without UV irradiation and the treatment with nitric oxide synthase (NOS) inhibitors resulted in the significant decrease of MMPs production. From these results, we concluded that the production of MMPs by the UV irradiated HDF is regulated through the signaling pathway involving NO and cyclic GMP.