• 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.

• Journal of Microbiology and Biotechnology
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• v.17 no.2
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• pp.271-279
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• 2007

Black rice (Oryza sativa L. var. japonica) has been used in folk medicine in Asia. To understand the effects of black rice hydrolyzed peptides (BRP) from germinated black rice, we assessed the expression levels of about 20,000 transcripts in BRP-treated HaCaT keratinocytes using human 1A oligo microarray analysis. As a result, the BRP treatment showed a differential expression ratio of more than 2-fold: 745 were activated and 1,011 were repressed. One of the most interesting findings was a 2-fold increase in hyaluronan synthase 2 (HAS2) gene expression by BRP. Semiquantitative RT-PCR showed that BRP increased HAS2 mRNA in dose-dependent manners. ELISA showed that BRP effectively increased hyaluronan (HA) production in HaCaT keratinocytes.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.741-762
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• 2003

Ginsenosides, the major active ingredients of ginseng, show a variety of biomedical efficacies such as anti-aging, anti oxidation and anti-inflammatory activities. To understand the effects of compound K (20-O-D-glucopyranosyl-20 (S)-protopanaxadiol), one of the major metabolite of ginsenosides on the skin, we assessed the expression level of ∼ 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 21 genes, which have been reported to be involved in the organization of ECM structure as well as defense responses in human skin cells. One of the most interesting findings is 2-fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1, 3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. The human clinical study indicates that topical application of compound K-containing oil-in-water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti-aging effects by the induction of HAS2 gene expression and following hyaluronan synthase.

• 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.

• Journal of Applied Biological Chemistry
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• v.42 no.2
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• pp.92-96
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• 1999

To study the regulatory mechanism of isoprenoid (carotenoid) biosynthesis, we have compared the expression patterns of nine isoprenoid biosynthetic genes in Korean red pepper (Capsicum. annuum cv. NocKaung). The expression of geranylgeranyl pyrophosphate synthase gene was initially induced at early ripening stage (I1) and was rather slightly decreased during pepper fruit ripening. The ex-pression of phytoene synthase gene was strongly induced at semi-ripening stage (I2) and the phytoene desaturase transcript was maximally induced at the fully ripened stage (R). Our results suggest that genes encoding two 3-hydroxy-3-methylglutaryl-CoA reductase isozymes (HMGR1 and HMGR2) and farnesyl pyrophosphate synthase might be not so critical in pepper carotenoid biosynthesis but three genes encoding geranylgeranyl pyrophosphate synthase, phytoene synthase and phytoene desaturase were induced in a sequential manner and coordinately regulated during the ripening of pepper fruit.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.635-639
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• 2024

Skin aging results from complex interactions of intrinsic and extrinsic factors, leading to structural and biochemical changes such as wrinkles and dryness. Ultraviolet (UV) irradiation leads to the degradation of hyaluronic acid (HA) in the skin, and the fragmented HA contributes to inflammation. This study revealed that the synergistic combination of carnosine and retinol (ROL) increases HA production in normal human epidermal keratinocytes (NHEKs) by upregulating hyaluronan synthase 2 (HAS2) gene transcription. Simultaneously, the combined treatment of carnosine and ROL significantly attenuates UVB-induced prostaglandin E₂ (PGE₂) synthesis in NHEKs. A significant correlation exists between the increase of HA synthesis and the inhibition of PGE₂ production. This study suggests that combined treatment of carnosine and ROL can improve skin aging phenotypes associated with UVB irradiation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.1 s.55
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• pp.7-15
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• 2006

In this study, the effect of oligopeptide ($Oligosproutin^{(R)}$) from sprouted black rice was evaluated for possible improvement in skin elasticity. We examined the changes in gene expression on oligopeptide-treated HaCaT cells using DNA microarray analysis. As a result, oligopeptide treatment showed a differential expression ratio of more than 2-fold : 745 genes were activated and 1011 genes were repressed. One of the most interesting findings is a 2-fold increase in hyaluronan synthase 2 (HAS 2) gene expression by oligopeptide. We also found that oligopeptide increased cell proliferation, HAS2 mRNA expression and intracellular ROS scavenging activity in HaCaT cells. A human clinical study which oil-in-water emulsion with oligopeptide was topically applied showed significant increase in skin elasticity. These results suggest that the sprouted black rice oligopeptide ($Oligosproutin^{(R)}$) can be effective anti-aging ingredient for cosmetics.

• 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.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.215.2-215.2
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• 2000

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.301-305
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• 2003

Nitric oxide (NO) is an important bioactive agent that mediates a wide variety of physiological and pathophysiological events. NO overproduction by inducible nitric oxide synthase (iNOS) results in severe hypotension and inflammation. This investigation is part of a study to discover new iNOS inhibitors from medicinal plants using a macrophage cell culture system. Two sesquiterpenes (1 and 2) were isolated from Artemisia iwayomogi (Compositae) and were found to inhibit NO synthesis ($IC_{50} 3.64 \mu g/mL and 2.81 \mu$g/mL, respectively) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Their structures were identified as 3-Ο-methyl-iso-secotanapartholide (1) and iso-secotanapartholide (2). Compounds 1 and 2 inhibited the LPS-induced expression of the iNOS enzyme in the RAW 264.7 cells. The inhibition of NO production via the down regulation of iNOS expression may substantially modulate the inflammatory responses.