• The Korea Journal of Herbology
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• v.39 no.1
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• pp.23-29
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• 2024

Objectives : Polyporus umbellatus is a medicinal mushroom that has been used for over thousands years in Chinese medicine as a powerful diuretic to relieve fluid retention and edema. Dermal papilla is located at the bottom of the hair follicle and connected to the blood vessels where it gets the nutrients and oxygen to nurture hair follicle. This study examined the mechanism through which the ethanol extract of Polyporus umbellatus (EPU) promoted the proliferation of human dermal papilla cells (HHDPCs). Methods : To estimate the proliferative effects of EPU on HHDPCs, cell viability was estimated by thiazolyl blue tetrazolium bromide (MTT) assay. Western blotting was used to investgate the activation of ERK, phosphoinositide 3-kinase (PI3K)/Akt, β-catenin, GSK-3β and heme oxygenase-1 (HO-1). Cells were treated with inhibitors of ERK and Akt prior to EPU treatment. Results : EPU promoted the proliferation of HHDPCs and the phosphorylation of ERK and Akt in dose dependent manner. However, the proliferative effect of EPU on HHDPCs was inhibited by pre-treatment of ERK inhibitor (PD98059) and Akt inhibitor (LY294002). Furthermore, EPU respectively stimulated the protein expression of β-catenin and phosphorylated GSK-3β. EPU significantly increased the protein expression levels of proliferation and cytoprotection related genes such as Bcl-2, SIRT-1, and HO-1 in cells. Conclusion : This results suggest that EPU promoted the proliferation of HHDPCs via activating PI3K/Akt and Wnt/β-catenin signaling pathway in HHDPCs.

• Journal of Life Science
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• v.25 no.2
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• pp.231-236
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• 2015

Angiotensin II (AngII) is an essential hormone that affects vascular physiology. For example, stimulation of vascular smooth muscle cells (VSMCs) rapidly induces vasoconstriction and results in the up-regulation of blood pressure. Chronic stimulation of VSMCs with AngII also results in hypertrophy. In this study, we confirmed an involvement of phosphatidylinositol 3-kinase (PI3K)-dependent calcium mobilization in AngII-induced generation of reactive oxygen species (ROS). Stimulation of rat aortic smooth muscle cells (RASMCs) with AngII significantly induced the generation of ROS in a dose- and time-dependent manner. AngII-induced generation of ROS was completely abolished by pharmacological inhibition of PI3K (with LY294002), but inhibition of the ERK signaling pathway had no effect. AngII-induced calcium mobilization was completely blocked by inhibition of PI3K, whereas inhibition of the ERK signaling pathway by PD98059 was ineffective. Depletion of extracellular calcium or inhibition of the L-type calcium channel by nifedipine completely blocked AngII-induced calcium mobilization. Depletion of extracellular calcium by EGTA and incubation of RASMCs with calcium-free medium both significantly blocked AngII-induced ROS generation. Inhibition of the L-type calcium channel also significantly blocked AngII-induced ROS generation. These results suggest that AngII-induced ROS generation is regulated by calcium mobilization, which, in turn, is modulated by a PI3K/L-type calcium channel signaling pathway.

• Korean Journal of Plant Resources
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• v.31 no.6
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• pp.634-640
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• 2018

Aralia cordata (A. cordata), which belongs to Araliaceae, is a perennial herb widely distributed in East Asia. We evaluated the anti-inflammatory effect of stems (AC-S), roots (AC-R) and leaves (AC-L) extracted with 100% methanol of A. cordata and elucidated the potential signaling pathway in LPS-stimulated RAW264.7 cells. The AC-L showed a strong anti-inflammatory activity through inhibition of NO production. AC-L dose-dependently inhibited NO production by suppressing iNOS, COX-2 and $IL-{\beta}$ expression in LPS-stimulated RAW264.7 cells. AC-L inhibited the degradation and phosphorylation of $I{\kappa}B-{\alpha}$, which donated to the inhibition of p65 nuclear accumulation and $NF-{\kappa}B$ activation. Furthermore, AC-L suppressed the phosphorylation of ERK1/2 and p38. These results suggested that AC-L may utilize anti-inflammatory activity by blocking $NF-{\kappa}B$ and MAPK signaling pathway and indicated that the AC-L can be used as a natural anti-inflammatory drugs.

• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.155-159
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• 2017

Cudrania tricuspidata Bureau (Moraceae) is a traditional oriental medicine that has been widely used as anti-oxidant, anti-inflammatory and immunomodulatory in Korea. This study was performed that the 70% ethanol extract of the roots of C. tricuspidata (CTE) suppressed receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis, actin ring formation in RAW 264.7 cell lines. CTE significantly inhibited the JNK/mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells. Also, CTE inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1. Consequently, CTE suppresses osteoclast differentiation by inhibiting RANKL induced MAPK signaling pathways and disrupts the actin rings in mature osteoclasts. Thus, CTE can be used for the development of osteoporosis treatment drug with a natural material.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.148-156
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• 2013

The $PrP^C$ is expressed in many types of immune cells including monocytes and macrophages, however, its function in immune regulation remains to be elucidated. In the present study, we examined a role for $PrP^C$ in regulation of monocyte function. Specifically, the effect of a soluble form of $PrP^C$ was studied in human monocytes. A recombinant fusion protein of soluble human $PrP^C$ fused with the Fc portion of human IgG1 (designated as soluble $PrP^C$-Fc) bound to the cell surface of monocytes, induced differentiation to macrophage-like cells, and enhanced adherence and phagocytic activity. In addition, soluble $PrP^C$-Fc stimulated monocytes to produce pro-inflammatory cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6. Both ERK and $NF-{\kappa}B$ signaling pathways were activated in soluble $PrP^C$-treated monocytes, and inhibitors of either pathway abrogated monocyte adherence and cytokine production. Taken together, we conclude that soluble $PrP^C$-Fc enhanced adherence, phagocytosis, and cytokine production of monocytes via activation of the ERK and $NF-{\kappa}B$ signaling pathways.

• Korean Journal of Pharmacognosy
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• v.45 no.4
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• pp.288-293
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• 2014

The present study was conducted to evaluate the hair growth-promoting effect of Clitocybin A from mushroom Clitocybe aurantiaca with dermal papilla cells (DPCs), which play important roles in the regulation of hair cycle. Clitocybin A significantly increased the proliferation of immortalized rat vibrissa DPCs. Flow cytometry analysis revealed that Clitocybin A promoted cell-cycle progression through G0/G1 to S phase in immortalized rat vibrissa DPCs. In addition, Clitocybin A increased the level of cell cycle proteins such as cyclin D1, phospho-pRB, and phospho-CDK2. To elucidate the molecular mechanisms of Clitocybin A on the proliferation of DPCs, we examined the activation of wnt/${\beta}$-catenin signaling which is known to regulate hair follicle development, differentiation and hair growth. Clitocybin A activated wnt/${\beta}$-catenin signaling via the increase of phospho(ser552)-${\beta}$-catenin, phospho(ser675)-${\beta}$-catenin and phospho(ser9)-$GSK3{\beta}$. Furthermore, Clitocybin A markedly increased the activation of extracellular signal-regulated kinase (ERK). These results suggest that the Clitocybin A may induce hair growth by proliferation of DPCs via cell-cycle progression as well as the activation of Wnt/${\beta}$-catenin signaling and ERK pathway.

• Journal of The Korean Society of Integrative Medicine
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• v.12 no.1
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• pp.1-10
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• 2024

Purpose: Lycopene is abundantly contained in Tomatoes and is known for diverse biological activities such as antioxidant, anti-inflammatory, and anticancer effects. In this study, the antioxidative potential of lycopene was investigated through the induction of hemeoxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor2 (Nrf2) and upstream signaling molecules, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Aktin RAW 264.7 cells. Methods: The antioxidative potential of lycopene against oxidative stress and its molecular mechanisms were determined by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results: Lycopene treatment significantly attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS formation in a dose-dependent manner without any cytotoxicity. In addition, 50 µM of lycopene for 6 h treatment induced potent HO-1 expression and its transcription factor, Nrf2. MAPK and PI3K/Aktwere also analyzed due to their critical roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, phosphorylation of extracellular regulated kinase (ERK) was significantly induced by lycopene treatment while the activated status of c-Jun NH2-terminal kinase (JNK), p38, and Akt, were not given any effect. To confirm the antioxidative mechanism of HO-1 mediated by ERK activation, each selective inhibitor was employed in a protection assay, in which oxidative damage occurred by t-BHP. Lycopene, SnPP, and CoPP treatments reflected accelerated HO-1 expression could be a protective role against oxidative damage-initiated cell death. A selective inhibitor for ERK significantly inhibited the lycopene-induced cytoprotective effect but selective inhibitors for other signaling molecules did not attenuate the rate of t-BHP-induced cell death. Conclusion: In conclusion, lycopene potently scavenged intracellular ROS formation and enhanced the HO-1 mediated antioxidative potential through the modulation of Nrf2, MAPK signaling pathway in RAW 264.7 cells.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.1013-1014
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• 2005

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.95.1-95.1
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• 2007

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• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.62-62
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• 2004