• Journal of Life Science
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• v.25 no.9
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• pp.976-983
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• 2015

Achyranthoside C dimethyl ester (ACDE) is an oleanolic acid glycoside from Achyranthes japonica which has been used in traditional medicine for the treatment of edema and arthritis. In this study, we investigated the anti-inflammatory effects of ACDE in RAW264.7 macrophages. ACDE significantly induced heme oxygenase-1 (HO-1) gene expression in RAW264.7 cells, while ACDE improved LPS-induced toxicity of cells. And ACDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Further study demonstrated that ACDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) (LY294002), c-Jun kinase (JNK) (SP600125), extracellular signal regulated kinase (ERK) (PD98059) and p38 kinase (SB203580). Moreover, ACDE phosphorylated Akt, JNK, ERK, and p38 MAPK. In addition, ACDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression in a dose-dependent manner. The inhibitory effects of ACDE on iNOS expression were abrogated by small interfering RNA (siRNA)-mediated knock-down of HO-1. Therefore, these results suggest that ACDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/MAPK-Nrf2 signaling pathway. These findings could help us to understand the active principle included in the roots of A. japonica and the molecular mechanisms underlying anti-inflammatory action of ACDE.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.46-52
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• 2023

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E₂ (PGE₂) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE₂ by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

• Journal of Life Science
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• v.30 no.10
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• pp.877-885
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• 2020

Lentinuls edodes has been used for traditional food and medicine around Asia, and a variety of biological effects have been reported. In this study, L. edodes water extract (LWE) was investigated for its anti-photodamage effect in HaCaT keratinocytes. To perform the necessary assays, L. edodes was extracted with distilled water for 8 hr at 40℃ in an extract tank. Anti-photodamage activity was assessed using a scratch wound healing assay, cell proliferation, and a reactive oxygen species (ROS) scavenging test and by measuring the mRNA and protein expression levels of matrix metalloproteinases (MMPs) and type I procollagen. MMPs and collagen expression are major markers of UV-induced photodamage in skin. Prior to photodamage analysis, the total polyphenol and β-glucan contents of the LWE were evaluated and found to be 4.64 mg GAE/g DW and 165.96 mg/g, respectively. Treatment with LWE induced cell migration and cell proliferation in UV-irradiated HaCaT cells, and LWE effectively scavenged the ROS induced by H₂O₂ and UVB irradiation in HaCaT cells. UVB irradiation induced ROS generation and led to increased production of MMP-1 and MMP-9 and to decreased collagen production in human keratinocytes. Treatment with LWE upregulated the expression levels of MMP-1, MMP-9, and type I procollagen in UVB-irradiated HaCaT cells. This study suggests that LWE could be used to develop cosmetic materials with anti-photodamage effects.

• Journal of Life Science
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• v.28 no.8
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• pp.992-998
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• 2018

Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

• Journal of Life Science
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• v.19 no.7
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• pp.949-955
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• 2009

Mucosal epithelia sense external stress signals and transmit them to the intracellular cascade responses. Ribotoxic stress-producing chemicals such as deoxynivalenol (DON) or other trichothecene mycotoxins have been linked with gastrointestinal inflammatory diseases by Fusarium-contamination. The purpose of this study was to test the hypothesis that DON evokes the epithelial sentinel signals of RNA-dependent protein kinase (PKR) and early growth response gene 1 (EGR-1), which together contribute to the pro-inflammatory cytokine interleukin 8 (IL-8) in human intestinal epithelial cells. PKR suppression by the dominant negative PKR expression attenuated DON-stimulated interleukin-8 production. Moreover, 1L-8 transcriptional activation by DON was also reduced by PKR inhibition in the human intestinal epithelial cells. Treatment with the PKR inhibitor also suppressed EGR-1 promoter activity, mRNA and protein induction, although mitogen-activated protein (MAP) kinases such as extracellular signal-regulated protein kinases (ERK) 1/2, p38, c-Jun N-terminal Kinase (INK) were little affected or even enhanced in presence of a PKR inhibitor. These patterns were also compared in the EGR-1-suppressed cells, which showed much more suppressed production of 1L-8. All things taken into consideration, DON-activated sentinel signals of EGR-1 via PKR mediated interleukin-8 production in human intestinal epithelial cells, which provide insight into the possible general mechanism associated with mucosal inflammation as an intestinal toxic insult by ribotoxic trichothecene mycotoxins.

• Journal of Life Science
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• v.25 no.9
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• pp.961-969
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• 2015

Epigallocatechin gallate (EGCG), the main catechin in green tea, has been shown to have some beneficial effects against various human diseases, including diabetes, neurodegenerative disorders, cancer, cardiovascular disease and obesity. To investigate the mechanism of the suppressive effects of EGCG on inflammatory response in macrophages, alterations on the levels of nitric oxide (NO) regulatory factors and inflammatory cytokines were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells. No significant toxicity was detected in RAW264.7 cells treated with 100–400 μM EGCG. Moreover, the optimal concentration of LPS was determined to be 1 μg/ml based on the results of cell viability assay, NO assay and IL-6 enzyme-linked immunsorbent assay (ELISA). Furthermore, NO levels decreased significantly by 68.2% in the 400 μM EGCG/LPS treated group, while the level of inducible nitric oxide synthase (iNOS) expression decreased by 12-17% in the 200 and 400 μM EGCG/LPS treated group. A significant decrease in transcription of pro-inflammatory cytokines (TNF- α and IL-1β) and anti-inflammatory cytokine (IL-10) was also detected in the EGCG/LPS treated group. However, IL-6 transcript and protein was maintained at a constant level when in the LPS treated group relative to the EGCG/LPS treated group. Overall, these results suggest that the differential regulation of inflammatory cytokines is an important factor influencing the suppressive effects of EGCG against LPS-activated inflammatory response in RAW264.7 cells.

• Journal of Life Science
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• v.26 no.12
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• pp.1422-1430
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• 2016

This study was performed to investigate the modulatory effects of two prototypes of Panax ginseng saponin fractions, 20(S)-protopanaxadiol saponins (PDS) and 20(S)-protopanaxatriol saponins (PTS), on the induction of inflammatory mediators in lipopolysaccharide (LPS)-treated RAW264.7 murine macrophage cells. For this purpose, RAW264.7 cells were treated with LPS ($10{\mu}g/ml$) before, after, or simultaneously with PDS or PTS ($150{\mu}g/ml$), and the released level of nitric oxide (NO) and expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated. When RAW264.7 cells were treated with LPS and ginseng saponin fractions simultaneously for 24 hr, PTS, compared to PDS, more strongly attenuated the NO production induced by LPS treatment. When the cells were pretreated with LPS for 2 hr followed by PDS or PTS treatment for 24 hr, both ginseng saponins strongly reduced NO release. The pretreatment of RAW264.7 cells with PDS or PTS for 2 hr followed by LPS treatment for 24 hr significantly attenuated the LPS-induced production of NO. PTS showed stronger inhibitory potency to NO generation than PDS. Our western blot experiment showed that both PDS and PTS ($150{\mu}g/ml$) also significantly down-regulated the expressions of iNOS and COX-2 induced by LPS treatment. Our results suggest that both PDS and PTS possess strong protective effects against LPS-stimulated inflammation and that their protective effects are mediated by the suppression of NO synthesis via down-regulation of pro-inflammatory enzymes, iNOS, and COX-2 in the RAW264.7 cells.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.37 no.3
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• pp.199-210
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• 2011

This study was conducted to develop functional sources of herbal cosmetics for treatment of skin aging and inflammatory disorders using volatile flavor extracts of four different herbal medicinal prescriptions including Cnidium officinale Makino (COM), Angelica gigas Nakai (AGN), Mentha arvense L. (MAL), Artemisiae argyi Folium (AAF), Paeonia lactiflora Pall (PLP), Rehmanniae Radix Preparata (RRP), Scutellaria baicalensis Georgi (SBG), Panax ginseng C.A. Meyer (PGM), Glycyrrhiza uralensis Fisch (GUF). The volatile flavor extracts of four different herbal medicinal prescriptions (HH-1: COM, AGN, PLP, RRP, HH-2: COM, AGN, PLP, RRP, SBG, PGM, GUF, HH-3: COM, AGN, MAL, AAF, HH-4: COM, AGN, MAL, AAF, SBG, PGM, GUF) were extracted using SDE and their antioxidant and anti-inflammatory effects were measured by using DPPH radical and SLO, respectively. As a result, HH-2 showed moderate DPPH radical scavenging activity (68.24 %) and the strongest SLO inhibitory activity (83.96 %) at 100 ${\mu}g$/mL. Moreover, HH-2 of four different prescriptions significantly inhibited NO production on LPS-stimulated RAW 264.7 cells in a dose-dependent manner without considerable cell cytotoxicity at range of 2.0 ~ 50 ${\mu}g$/mL. Additionally, HH-2 also effectively suppressed the production of $PGE_2$ and IL-6, which are responsible for promoting the inflammatory process. Major volatile components of HH-2 were identified as eugenol, paeonol, butyl phthalide, ${\beta}$-eudesmol and butylidene dihydrophthalide by GC-MS analysis. Thus, these results suggest that HH-2 may be useful as a potential source of anti-inflammatory agents in herbal medicinal cosmetics.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.3
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• pp.249-258
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• 2018

Airborne pollution causes oxidative damage, inflammation, and premature aging of skin. Resveratrol is a polyphenol compound that has various biological activities such as antioxidant, anti-inflammation, and anti-melanogenic activities but it is unstable to heat and light. Resveratryl triacetate (RTA) is a new cosmetic ingredient that is more stable than resveratrol and its skin safety and whitening efficacy have been reported previously. The purpose of this study was to examine the effects of resveratrol and resveratryl triacetate (RTA) on the inflammatory responses of human epidermal keratinocytes (HEKs) exposed to airborne particulate matters with a diameter of < $10{\mu}m$ (PM10). Cultured HEKs were exposed to PM10 in the absence or presence of resveratrol and RTA. Assays were undertaken to determine cell viability, the production of reactive oxygen species (ROS), and the expression of inflammatory cytokines. PM10 treatment decreased cell viability, and increased the expression of pro-inflammatory cytokines such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and interleukin-8 (IL-8). Resveratrol and RTA reduced cell death and ROS production induced by PM10. PM10-induced mRNA expression of the inflammatory cytokines was either attenuated (IL-6), or enhanced ($IL-1{\beta}$), or unaffected ($TNF-{\alpha}$ and IL-8) by resveratrol and RTA. PM10-induced IL-6 protein expression was attenuated by resveratrol and RTA. This study suggests that resveratrol and RTA have activities regulating cell damage and inflammatory responses of the skin exposed to airborne particulate matters.

• Korean Journal of Food Science and Technology
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• v.50 no.5
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• pp.535-542
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• 2018

The current study investigated the beneficial effects of 15 essential oils isolated from tree branches, leaves, and flowers. Among these oils, clove bud and Illicium anisatum oils showed the most potent anti-oxidant effects on 1,1-diphenyl-2-picrylhydrazyl and 2,2'azinbis-(3-ethyl-benzothiazoline-6-sulfonic acid) radical scavenging activities. Next, we evaluated the antibacterial effects of 15 essential oils on Staphylococcus aureus, Listeria monocytogenes, Escherichia coli O157:H7, Salmonella typhimurium, and Streptococcus mutans. Clove bud significantly decreased growth of 5 bacterial strains. In addition, clove bud, Magnolia kobus, Picea abies and Chamaecyparis obtuse significantly reduced growth of the fungi, Aspergillus fumigatus, Aspergillus ochraceus, Candida albicans and Trichophyton rubrum. Additionally, clove bud also remarkably reduced the expression of cyclooxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW264.7 cells. These results indicate that essential oils isolated from trees, which exhibit antioxidant, antibacterial, antifungal and anti-inflammatory properties, may be potentially useful in the development of cosmetic ingredients.