• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.26 no.1
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• pp.75-81
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• 2013

Objectives: Hyaluronic acid, high molecular glycosaminoglycan, exists in extracellular matrix of tissue, especially, in skin and has been known to be deeply involved in skin hydration. In this study, we investigated the effect of methanol extract of Hwang-gi, Astragalus membranaceus root, on hyaluronic acid production in human keratinocyte HaCaT cells. Methods: We determined hyaluronic acid synthase 2 gene expression and hyaluronic acid production in HaCaT cells by using RT-PCR and ELISA, respectively. Results: Hwang-gi extract didn't show the toxicity to HaCaT cells within the treated concentration and increased the hyaluronic acid synthase 2 gene expression and hyaluronic acid production. Conclusions: Hyaluronic acid production increased by Hwang-gi could be, partially, contribute to the moisturing effect in skin by it.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.31 no.1
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• pp.32-41
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• 2018

Objectives : Hyaluronic acid(HA) is a mucopolysaccharide, occuring naturally in living organisms. It is one of the most hydrophilic molecules, so it has been known as being related to skin hydration and skin aging. The purpose of this study is to examine the effects of Angelica gigas(A. gigas) ethanol extract on hyaluronic acid synthesis. Methods : To determine cytotoxicity and hyaluronic acid synthase 2 gene expression, hyaluronic acid production in HaCaT cells, MTT assay and RT-PCR ELISA was used. Results : There were no cytotoxicity in $50{\mu}g/ml$ concentration A. gigas extract in MTT assay. Hyaluronic acid synthase 2(HAS2) gene expression was increased by all treated concentration A. gigas extract. Hyaluronic acid production was higher than control group in $50{\mu}g/ml$ & $100{\mu}g/ml$ concentration A. gigas extract. Conclusions : Hyaluronic acid production was increased by A. gigas extracts. Therefore, We suggest that A. gigas can make a contribution to the moisturizing effect on human skin.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.1
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• pp.32-40
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• 2015

Objectives : Hyaluronic acid(HA) is a mucopolysaccharide, occuring naturally in living organisms. It is one of the most hydrophilic molecules, so it has been known as being related to skin hydration and anti-aging. The purpose of this study is to examine the effects of Angelica acutiloba ethanol extract on hyaluronic acid synthesis. Methods : To determine cytotoxicity and hyaluronic acid synthase 2 gene expression, hyaluronic acid production in HaCaT cells, MTT assay and RT-PCR ELISA was used. Results : There was no cytotoxicity in $50{\mu}g/ml$ concentration Angelica acutiloba extract in MTT assay. Hyaluronic acid synthase 2(HAS2) gene expression was increased by all treated concentration Angelica acutiloba extract. Hyaluronic acid production was higher in $50{\mu}g/ml$ & $100{\mu}g/ml$ concentration Angelica acutiloba extract than control group. Conclusions : Hyaluronic acid production was increased by Angelica Acutiloba extracts. Therefore, We suggest that Angelica acutiloba can make a contribution to the moisturing effect on human skin. Conclusions : Hyaluronic acid production was increased by Angelica Acutiloba extracts. Therefore, We suggest that Angelica acutiloba can make a contribution to the moisturing effect on human skin.

• Journal of Microbiology and Biotechnology
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• v.19 no.3
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• pp.299-306
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• 2009

Dissolved oxygen (DO) has a significant effect on the molecular weight of hyaluronic acid (HA) during the fermentation of Streptococcus zooepidemicus. Therefore, to further investigate the effect of DO on the yield and molecular weight of HA, this study compared the metabolic flux distribution of S. zooepidemicus under aerobic conditions at various DO levels. The metabolic flux analysis demonstrated that the HA synthesis pathway, considered a dependent network, was little affected by the DO level. In contrast, the fluxes of lactate and acetate were greatly influenced, and more ATP was generated concomitant with acetate at a high DO level. Furthermore, the has gene expression and HA synthase activity were both repressed under anaerobic conditions, yet not obviously affected under aerobic conditions at various DO levels. Therefore, it was concluded that the HA molecular weight would seem to depend on the concomitant effect of the generation of ATP and reactive oxygen species. It is expected that this work will contribute to a better understanding of the effect of the DO level on the mechanism of the elongation of HA chains.

• Journal of Life Science
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• v.25 no.8
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• pp.880-888
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• 2015

Foeniculum vulgare (FV) has long been used in traditional medicine for the treatment of inflammatory diseases. In addition, it is usually known as an important medicinal and aromatic plant widely used as a carminative, digestive, lactogogue, and diuretic, and for treating respiratory and gastrointestinal disorders. The skin barrier protects against the invasion of pathogens, fends off chemical and physical assaults, and protects against extensive water loss. In this study, the effects of solvent-fractionated FV fruits on strengthening the skin barrier and maintaining moisture, as well as their antifungal activity, were investigated in human keratinocyte (HaCaT) cells. The expression of involucrin, loricrin, filaggrin, hyaluronic acid synthase, human β defensin, and cathelicidin genes and proteins was measured by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The production of hyaluronic acid was determined by enzyme-linked immunosorbent assay (ELISA). The butanol fraction increased the expression of involucrin and filaggrin. Both the ethyl acetate and the butanol fractions increased hyaluronic acid production by promoting the expression of hyaluronic acid synthase-1. Although the antimicrobial peptides were increased by FV crude extract and its fractions, the samples did not show a significant effect compared to the normal group. These results suggest that the butanol fraction of FV could be very useful in cosmetics for the treatment of dermatological diseases.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.30 no.1
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• pp.106-117
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• 2017

Objectives : 갈근의 피부 보습 효과에 대해 알아보기 위해 본 연구를 진행하였다. Methods : HaCaT 세포주에 갈근 에탄올 추출물을 처리하였고 Retinoic Acid $1{\mu}M$을 양성 대조군으로 사용하였다. MTT assay, RT-PCR, Hyaluronidase enzyme assay, HA-ELISA kit를 통해 Hyaluronic Acid의 합성량, Hyaluronidase 저해율, 농도별 Hyaluronic Acid 생성량을 측정하였다. 더불어 실제로 피부에 도포 시 보습 능력이 있는지 등에 대하여 확인하였다. Results : 갈근 에탄올 추출물은 뚜렷한 세포독성을 나타내지는 않았고, 모든 농도에서 Hyaluronic Acid 합성과 관련된 hyaluronic acid synthase 2 유전자가 발현되었고, 실제로 Hyaluronic Acid가 생성되는 것을 확인하였다. 임상 효능 평가에서는 유의성 있는 결과를 얻을 수는 없었다. Conclusions : 갈근을 한방 외용제로 사용할 때 유의성 있는 효과를 나타낼 수 있을 것으로 기대할 수 있으며, 실험 결과를 토대로 갈근의 최적 사용 농도를 결정하기 위한 추가적 연구와 복합 처방으로 사용했을 경우에 대한 연구가 추가적으로 진행된다면 한방 외용제로서 잠재적인 가치가 있을 것으로 사료된다.

• Applied Chemistry for Engineering
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• v.33 no.6
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• pp.557-562
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• 2022

Hyaluronic acid (HA) is a mucopolysaccharide, occurring naturally in living organisms. It is one of the most hydrophilic molecules, so it has been known as being related to skin hydration and skin aging. The purpose of this study was to examine the effects of Cimicifuga heracleifolia ethanol extract on the hyaluronic acid synthesis and the inhibition of hyaluronidase activity. To determine cytotoxicity, hyaluronic acid synthase 2 (HAS2) gene expression, HA production and, hyaluronidase inhibitory effects, 3-(4,5-dimethylthiazol-2-ly)-2,5-diphenyl tetrazolium bromide (MTT) assay, real time - polymerase chain reaction (RT-PCR), hyaluronic acid enzyme linked immunosorbent assay (HA-ELISA), and hyaluronidase assay were used, respectively. When the Cimicifuga heracleifolia extract was treated in the HaCaT cells up to 500 ㎍/mL concentration, cytotoxicity was confirmed by the Cimicifuga heracleifolia extract at concentrations above 200 ㎍/mL. Therefore, the optimum concentration of all experiments used in this study was determined to be 200 ㎍/mL. HAS2 gene expression increased by Cimicifuga heracleifolia extract in a concentration-dependent manner at all treatment concentrations. The production rate of HA was tended to decrease at the highest concentration of 200 ㎍/mL. The hyaluronidase activity inhibition effect of Cimicifuga heracleifolia extract was very high compared to the control group. Based on these results, Cimicifuga heracleifolia extract was expected to have a moisturizing effect on human skin and special attention should be paid to the determination of the concentration of Cimicifuga heracleifolia when developing cosmetic materials using it.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.39 no.4
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• pp.281-288
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• 2013

Hyaluronic acid (HA) is one of the major extracellular matrix components in skin. The HA content is reported to decline with age, which may contribute to decrease in skin moisture, wrinkle formation and the decrease in elasticity of the skin. Among the family of HA synthase genes (HAS-1, 2, 3) identified so far, HAS-2 plays crucial roles in the regulation of HA synthesis in human skin fibroblasts. In this study, we elucidated the effects of ferulic acid isolated from Cnidium officinale on HA production. Semi-quantitative RT-PCR and quantitative real-time PCR showed that ferulic acid increased mRNA level of HAS-2 gene and ELISA assay also revealed that ferulic acid increased HA production in human skin fibroblasts. Our study suggests that ferulic acid might prevent age-dependent skin deteriorations such as wrinkles, dryness and elasticity decrease, all of which could be ascribed to the reduction of the HA content in human skin.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.368-379
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• 2022

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

• BMB Reports
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• v.54 no.2
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• pp.136-141
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• 2021

Thyroid eye disease (TED) is a complex autoimmune disease with a spectrum of signs. we previously reported that trisialoganglioside (GT)1b is significantly overexpressed in the orbital tissue of TED patients, and that exogenous GT1b strongly induced HA synthesis in orbital fibroblasts. However, the signaling pathway in GT1b-induced hyaluronic acid synthase (HAS) expression in orbital fibroblasts from TED patients have rarely been investigated. Here, we demonstrated that GT1b induced phosphorylation of Akt/mTOR in a dose-dependent manner in orbital fibroblasts from TED patients. Both co-treatment with a specific inhibitor for PI3K and siRNA knockdown of TLR2 attenuated GT1b-induced Akt phosphorylation. GT1b significantly induced HAS2 expression at both the transcriptional and translational level, which was suppressed by specific inhibitors of PI3K or Akt/mTOR, and by siRNA knockdown of TLR2. In conclusion, GT1b induced HAS2 in orbital fibroblasts from TED patients via activation of the PI3K-related signaling pathway, dependent on TLR2.