• Korean Journal of Medicinal Crop Science
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• v.22 no.6
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• pp.457-462
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• 2014

Prostaglandin (PG) $E_2$ is an important mediator of skin wound healing without excessive scarring and gastric ulcer healing. However, $PGE_2$ has a short lifetime in vivo because it is metabolized rapidly by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Ethanol extract of Eriobotryae folium (EFEE) elevated intracellular and extracellular $PGE_2$ levels in HaCaT cells and inhibited 15-PGDH ($ED_{50}$ : $168.4{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$ : $250.0{\mu}g/mL$). Real-time PCR analysis showed that mRNA expression of cyclooxygenase (COX)-1 and COX-2 enzymes were increased and prostaglandin transporter (PGT) was decreased in HaCaT cells by EFEE. Moreover, wound healing effect of EFEE ($168.4{\mu}g/mL$) was comparable to that of TGF-${\beta}1$ (300 pg/mL) as a positive control. These results demonstrate that EFEE may be valuable therapeutic materials for the treatment of $PGE_2$ level dependent diseases.

• YAKHAK HOEJI
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• v.45 no.3
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• pp.310-319
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• 2001

To compare skin irritation and cytotoxicity of anti-wrinkle agents, we examined skin irritation of six anti-wrinkle agents (ascorbic acid, glycolic acid, all trans-retinoic acid, ginseng extract, retinol, EB) in New Zealand white rabbit. Cytotoxicity of these agents was determined by MTT [tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] at multi-time points in cultured HaCaT cell, a human immortalized keratinocyte cell. We then analyzed correlation between skin irritation and cytotoxicity by spearman's rank correlation analysis. All trans-retinoic acid showed the highest primary irritation index (0.92) in skin irritation test. Being all the six agents not irritant, retinal showed the most cytotoxic agents. The correlation between skin irritation and cytotoxicity ($IC_{50}$/ at different time point was 0.814, 0.757, 0.814 and 0.7 at 3, 24, 48 and 72 h, respectively. We also fecund that IC$_{20}$ and IC$_{80}$ of these agents showed similar correlation with skin irritation. These results therefore demonstrated that there is close correlation between skin irritation and cytotoxicity $IC_{50}$/ value by MTT in HaCaT cell at early time points by anti-wrinkle agents or IC$_{20}$ value. $IC_{50}$/ at earily time point or IC$_{20}$ values may be reliable alternative determinant of skin irritation.n.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.869-876
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• 2022

The skin, which is the largest organ of the human body, is in direct contact with pollutants in the surrounding atmosphere. Meanwhile, 1-nitropyrene (1-NP), the most abundant nitro-polycyclic aromatic hydrocarbon found in particulate matter, is known to have carcinogenic effects; however, studies on its toxicity in human and canine skin are still needed. In this study, we investigated 1-NP-induced apoptosis and inflammatory pathways in HaCaT cells. In addition, we also measured the cytoprotective effect of methyl gallate (MG), which is widely distributed in medicinal and edible plants and is well known for its anti-inflammatory and antioxidant properties. MG inhibited 1-NP-induced cell death and apoptosis pathways, including the cleavage of PARP and activation of caspase-3, -7, and -9. MG also suppressed 1-NP-induced COX-2 expression and phosphorylation of mitogen-activated protein kinases (MAPKs) and MAPK kinases (MAPKKs). Our findings suggest that 1-NP induces skin toxicity in human and canine through apoptosis and inflammatory responses, and moreover, that this can be prevented by treatment with MG.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.699-704
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• 2012

Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of $Annona$ $muricata$ L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and $DPPH^*$radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (P<0.05) positive correlation of phenolic compounds with free radical scavenging potential. The results revealed that the extract was moderately cytotoxic to normal cells with a mean IC50 value of 52.4 ${\mu}g$ when compared with those obtained for cancerous cells (IC50 values of 29.2 ${\mu}g$ for MDA-MB-435S and 30.1 ${\mu}g$ for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of $Annona$ $muricata$. Isolation of the active metabolites from the extract is in prospect.

• Korean Journal of Pharmacognosy
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• v.41 no.4
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• pp.255-263
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• 2010

Kojongsi persimmon (Diospyros kaki) is the major cultivar of astringent persimmon in southern of Korea. Kojongsi persimmon leaf has been traditionally used for acute and chronic diseases in Oriental countries. The purpose of this study was undertaken to investigate the antioxidative activities of the extract of Kojongsi persimmon leaf during growth. We investigated the antioxidant effects of the persimmon leaf extracts during growth on total polyphenol, total flavonoid, electronic donating ability (DPPH), nitrite (NO) scavenging and superoxide dismutase (SOD)-like activity. The next, we investigated the possible cell protective effects of the persimmon extract treatment against ultraviolet B (UVB)-induced injury in HaCaT keratinocytes. The contents of total polyphenol and flavonoid in leaf extract of Kojongsi persimmon were increased in time-dependent manner. In Jun, DPPH and NO radical scavenging and SOD-like activities in the leaf extract of Kojongsi persimmon was increased to the highest. However, the antioxidant activities in persimmon varieties were not any difference. The cell cytotoxicity by UVB irradation in HaCaT keratinocytes was significantly increased with the compared to the control group. However, the treatment of leaf extract of Kojongsi persimmon in HaCaT keratinocytes was shown to protective effect against UVB-induced cell cytotoxicity. These results suggest that the leaf extract of Kojongsi persimmon has potent antioxidant activity, and protective effect against UVB-induced keratinocyte injury. Thus, these properties may be contributed in the care of acute and chronic diseases.

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.349-357
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• 2013

6'-O-galloylpaeoniflorin (GPF) is a galloylated derivate of paeoniflorin and a key chemical constituent of the peony root, a perennial flowering plant that is widely used as an herbal medicine in East Asia. This study is the first investigation of the cytoprotective effects of GPF against hydrogen peroxide ($H_2O_2$)-induced cell injury and death in human HaCaT keratinocytes. GPF demonstrated a significant scavenging capacity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, $H_2O_2$-generated intracellular reactive oxygen species (ROS), the superoxide anion radical ($O_2^-$), and the hydroxyl radical (${\cdot}$OH). GPF also safeguarded HaCaT keratinocytes against $H_2O_2$-provoked apoptotic cell death and attenuated oxidative macromolecular damage to DNA, lipids, and proteins. The compound exerted its cytoprotective actions in keratinocytes at least in part by decreasing the number of DNA strand breaks, the levels of 8-isoprostane (a stable end-product of lipid peroxidation), and the formation of carbonylated protein species. Taken together, these results indicate that GPF may be developed as a cytoprotector against ROS-mediated oxidative stress.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.3
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• pp.182-187
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• 2017

The purpose of the present study is a comparison of the antioxidant effects of Angelica gigas Korea (AG), Angelica sinensis of China (AS), and Angelica acutiloba of Japan (AA), and comparison of the effects of AG, AS and AA on tight-junction related genes in human keratinocyte HaCaT cells. All species showed a strong antioxidant effect, and AA was higher than AG and AS in antioxidant effects. The cytotoxicity was confirmed to be higher in AS than AG and AA at a concentration of $1,600{\mu}g/ml$ using the MTS assay in HaCaT cells. We analyzed the effects of AG, AS, and AA on mRNA expression levels of various tight-junction related genes in HaCaT cells. We found that no obvious changes in expression of Claudin 1, 3, 4, 6, 7, 8, Occludin, JAM-A, ZO-1, ZO-2, and tricellulin by treatment of all species, suggesting that there is less possibility of side effects and skin moisturizing effects due to changes in tight-junction gene expression. Our results suggest that AG, AS, and AA are thought to be effective in reducing the oxidative stress of the skin and preventing the aging of the skin.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.120-120
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• 2019

Allergic inflammatory disease has been increased by abnormal lifestyle and food habits. Especially, prevalence of atopic dermatitis (AD) has been elevated and treatment of AD has not been unclear. Red sweet pepper (RSP), named as Capsicum annuum L, has been known as having pharmacological effects such as antioxidant, detoxification and antibacterial effects. However, the beneficial effect of ethanolic extract of RSP on AD has not been partly examined yet. Therefore, the aim of this study was to investigate anti-inflammatory effects of RSP on AD in vitro and in vivo models. The treatment of RSP inhibited the secretion of inflammatory cytokine such as interleukin (IL)-6 and IL-8 in tumor necrosis factor (TNF)-${\alpha}$ and interferon (IFN)-${\gamma}$-stimulated human keratinocyte (HaCaT cell). Also, RSP extract regulated 2,4-dinitroflorobenzene (DNFB)-induced AD-like skin lesions in BALB/c mice. Oral administration of RSP ameliorated DNFB-induced AD-like symptoms. In presented results indicated that RSP inhibited inflammatory cytokines in HaCaT cell and ameliorated AD-like skin lesion through suppression of symptom of DNFB-induced skin inflammation. Thus, RSP might be a potential therapeutic agent for AD.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.45-49
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• 2011

Objectives : The purpose of this study was to investigate the anti-aging effects on cultured human keratinocytes with Nelumbo nucifera extracts. Methods : Each parts of leaves, flowers and stamen were extracted with water or 70% ethanol. These extracts were tested for cell viability on HaCaT cells (human keratinocyte line) by MTT assay. We investigated the effects of Ultraviolet-B (UVB) irradiation on cytotoxicity and lipid peroxidation in cultured skin keratinocytes. Results : The ethanol extract of Nelumbo nucifera flowers showed maximun cell viability as 111.39% in 30 ug/ml concentration. The water extracts of stamen, flowers, leaves showed cell viability as 107.12, 101.65, 101.46%, respectively. HaCaT keratinocytes were survived 63.06% at $20mJ/cm^2$ UVB irradiation. The cell membrane lipid peroxidation was measured by accumulation malondialdehyde (MDA). The levels of MDA were decreased by the ethanol extract of Nelumbo nucifera flowers and the water extracts of stamen. Conclusions : These finding suggest that the ethanol extract of Nelumbo nucifera flowers prevent anti-aging effects on cultured human keratinocytes during UVB irradiation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.247-251
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• 2004

UV radiation exerts various influences in the skin, including photoaging and inflammation (1). The MMPs (Matrix metalloproteinases), which are induced by UV irradiation, can degrade matrix proteins, and these results in a collagen deficiency in photodamaged skin that leads to skin wrinkling. It has been known that the production of PGE$_2$ stimulates MMPs expression, and inhibits procollagen (2). Thus, it is possible that the induction of MMPs and the inhibition of matrix protein synthesis by UV -induced PGE$_2$ may play some role in UV-induced collagen deficiency in photoaged skin. Fructose-1,6-diphosphate (FDP), a glycolytic metabolite, is reported to have cytoprotective effects against ischemia and postischemic reperfusion injury of brain and heart, presumably by augmenting anaerobic carbohydrate metabolism (3). And also, FDP significantly prevent skin aging by decreasing facial winkle compared with vehicle alone after 6 months of use. We studied the mechanism of anti-aging effect of FDP on UVB-irradiated HaCaT keratinocyte model. FDP has protective role in UVB injured keratinocyte by attenuating prostaglandin E$_2$ (PGE$_2$) production and COX-2 expression. And FDP also suppressed UVB-induced MMP-2 expression. Further, to delineate the inhibition of UVB-induced COX-2 and MMPs expression with cell signaling pathways, treatment of FDP to HaCaT keratinocytes resulted in marked inhibition of UVB-induced phosphorylation of ERK1/2, JNK. It also prevents UV induced NFB translocation, which are activated by cellular inflammatory signal. Our results indicate that FDP has protecting effects in UV-injured skin aging by decreasing UVB-induced COX-2 and MMPs expression, which are possibly through blocking UVB-induced signal cascades.