• International Journal of Oral Biology
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• v.45 no.4
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• pp.179-189
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• 2020

Green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant with protective effects against neurotoxicity. However, it is currently unclear whether EGCG protects neuronal cells against radiation-induced damage. Therefore, the objective of this study was to investigate the effects of EGCG on ultraviolet (UV)-induced oxidative stress and apoptosis in PC12 cells. The effects of UV irradiation included apoptotic cell death, which was associated with DNA fragmentation, reactive oxygen species (ROS) production, enhanced caspase-3 and caspase-9 activity, and poly (ADP-ribose) polymerase cleavage. UV irradiation also increased the Bax/Bcl-2 ratio and mitochondrial pathway-associated cytochrome c expression. However, pretreatment with EGCG before UV exposure markedly decreased UV-induced DNA fragmentation and ROS production. Furthermore, the UV irradiation-induced increase in Bax/Bcl-2 ratio, cytochrome c upregulation, and caspase-3 and caspase-9 activation were each ameliorated by EGCG pretreatment. Additionally, EGCG suppressed UV-induced phosphorylation of p38 and rescued UV-downregulated phosphorylation of ERK. Taken together, these results suggest that EGCG prevents UV irradiation-induced apoptosis in PC12 cells by scavenging ROS and inhibiting the mitochondrial pathways known to play a crucial role in apoptosis. In addition, EGCG inhibits UV-induced apoptosis via JNK inactivation and ERK activation in PC12 cells. Thus, EGCG represents a potential neuroprotective agent that could be applied to prevent neuronal cell death induced by UV irradiation.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.266-274
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• 2022

Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.

• BMB Reports
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• v.55 no.8
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• pp.370-379
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• 2022

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.95-100
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• 2013

Objectives : The purpose of this study was to investigate antiaging and antioxidant effects on cultured human skin fibroblast with supercritical fluid extracts of Dendropanax morbifera, Corni fructus and Lycii Fructus. Methods : Supercritical fluid extraction (SFE) technique was applied to extract from three medicinal plants including stem of Dendropanax morbifera, Corni fructus and Lycii Fructus. Antioxidant activity of extract was evaluated by two different assays as 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and super oxide dismutase (SOD) like activities. These extracts were tested for cell viability on HS68 skin fibroblast by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. We investigated the effects of Ultraviolet-B irradiation on cytotoxicity, type 1 collagen, elastin level and oxidative damage in cultured human skin fibroblast (HS68). Recently, many studies have reported that elastin is also involved in inhibiting or repairing wrinkle formation, although collagen is a major factor in the skin wrinkle formation. Results : The extracts obtained dose-dependently increased the scavenging activity on DPPH radical scavenging activity and SOD like activity. The supercritical fluid extracts of complex herbal medicine showed low cytotoxicity as more than 100% cell viability in 100ppm/ml concentration. HS68 fibroblasts were survived 70% at $120mJ/cm^2$ UVB irradiation and treated tumor necrosis factor (TNF)-alpha. The levels of aging factors and cytotoxicity were decreased by supercritical fluid extract of complex herbal medicine. Conclusions : These results suggest that supercritical fluid extracts may have value as the potential antioxidant and antiaging medicinal plant.

• Archives of Plastic Surgery
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• v.49 no.3
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• pp.462-470
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• 2022

Background Reactive oxygen species cause serious damage to the physiological function of tissues. Determination of total antioxidant capacity of skin tissue is one of the determinants of damaged tissue function. Mast cells (MCs) are one of the groups of cells that are invited to the site of injury. The healing process begins with the rapid release of various types of MCs' intermediate factors at the site of injury. Bone marrow mesenchymal stem cell (BMMSC) production and secretion have been shown to regenerate the skin. The aim of this research was to evaluate the wound-healing and antioxidant effects of BMMSCs per MCs. Methods Fifty-four albino Wistar male rats were divided into three groups: (1) nonsurgery, (2) surgery, and (3) surgery + BMMSCs. Groups 2 and 3 were operated with a 3 × 8 cm flap and in group 3, cell injections (7 × 10⁹ cell injection at the time of surgery) were performed. After days 4, 7, and 15, percentage of the surviving tissue, histological characteristics, superoxide dismutase (SOD) activity, and amount of malondialdehyde (MDA) were measured in the groups. For results, Graph Pad Prism 8 software was used, and data were analyzed and compared by analysis of variance and Tukey test. Results BMMSCs' application decreased the amount of MDA, increased SOD activity and survival rate of the flaps, and improved the histological characteristics. Conclusion This study revealed the protective effects BMMSCs alongside MCs against oxidative stress on the survival of the flaps. However, for clinical use, more research is needed to determine its benefits.

• The Korea Journal of Herbology
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• v.37 no.6
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• pp.9-17
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• 2022

Objective : In modern society, liver diseases such as liver fibrosis are on the rise as inflammation and wound healing processes of the liver are repeated due to factors such as drinking, smoking, and stress. This study was conducted to evaluate the effect of Saenggangeonbi-tang (SGGBT) on thioacetamide (TAA)-induced liver fibrosis. Methods : The mice were divided into 4 groups for examination (n=6): Normal group (Nor), distilled water-treated liver fibrosis mice (Con), silymarin 50 mg/kg-treated liver fibrosis mice (Sily), SGGBT 200 mg/kg-treated liver fibrosis mice (S200). Liver fibrosis was established in the mice via TAA for 8 weeks (1 week 100 mg/kg, 2,3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg, three times a week, intraperitoneal injection) and they were administered silymarin and SGGBT (every day, oral administration) with the TAA. Results : SGGBT significantly decreased the levels of aspartate aminotransferase, alanine aminotransferanse, ammonia, and myeloperoxidase in serum increased by liver fibrosis. As a result of confirming H&E and MT staining, it was confirmed that SGGBT reduced damage and inflammatory cell infiltration in liver tissue, and alleviated changes in collagen fiber deposition and histological fibrosis. Also, it was confirmed through PAS staining that it reduced glycogen deposition in liver tissue. In addition, SGGBT significantly decreased the NADPH oxidases as well as significantly modulated the expression of MMP-2 and TIMP-2. Conclusions : These results suggest that SGGBT regulates the expression of MMP/TIMP protein through inhibition of oxidative stress and alleviates liver fibrosis by reducing collagen and glycogen deposition in liver tissue.

• Journal of the Korean Applied Science and Technology
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• v.40 no.1
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• pp.35-47
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• 2023

This study aimed to confirm the potential as a material for food, medicine, and cosmetics by measuring the physiological activity of the complex extract(Leonurus japonicus Houtt., Houttuynia cordata Thunberg and Citrus unshiu Markovich). The complex extract was with hot water, The evaluation of cytotoxicity, antioxidant, anti-inflammatory, and MAPKs of the extract was performed by using ELISA and western blot. Total polyphenols and flavonoid contents of complex extracts were 126.16 mg/g and 105.84 mg/g, respectively. The scavenging activities of DPPH and ABTS radical significantly increased in a dose-dependent in complex extracts. Compared to the control group, the complex extracts treatments significantly reduced concentrations of nitric oxide and inflammatory cytokine (i.e., IL-1β, TNF-α, and IL-6). Furthermore, the complex extracts treatments significantly reduced protein expression levels of MAPKs (i.e., ERK, JNK, and p38). The results indicate that the complex extract can be used for oxidative damage and inflammation. Thus, the results of this study can be used as basic data for composite materials for food, medicine, and cosmetics.

• Molecules and Cells
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• v.46 no.8
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• pp.513-525
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• 2023

Orange carotenoid protein (OCP) of photosynthetic cyanobacteria binds to ketocarotenoids noncovalently and absorbs excess light to protect the host organism from light-induced oxidative damage. Herein, we found that mutating valine 40 in the α3 helix of Gloeocapsa sp. PCC 7513 (GlOCP1) resulted in blue- or red-shifts of 6-20 nm in the absorption maxima of the lit forms. We analyzed the origins of absorption maxima shifts by integrating X-ray crystallography, homology modeling, molecular dynamics simulations, and hybrid quantum mechanics/molecular mechanics calculations. Our analysis suggested that the single residue mutations alter the polar environment surrounding the bound canthaxanthin, thereby modulating the degree of charge transfer in the photoexcited state of the chromophore. Our integrated investigations reveal the mechanism of color adaptation specific to OCPs and suggest a design principle for color-specific photoswitches.

• Molecules and Cells
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• v.46 no.6
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• pp.374-386
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• 2023

Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

• Journal of People, Plants, and Environment
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• v.22 no.1
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• pp.39-52
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• 2019

To evaluate the protective effect of collagen peptide-coated coffee extract on skin aging, cell viability was measured with a MTT assay using cultured CCD-986sk fibroblasts, and its effect on wrinkles in the skin of hairless mice induced by UVB-irradiation was examined. In addition, its effect on procollagen synthesis and anti-oxidative, and its inhibitory activity against collagenase, elastase, tyrosinase and MMP-1 were analysed. After the 30-minute topical treatment, the animals were exposed to UVB irradiation (60-100 mJ/cm²) for 4 weeks and its intensity increased during the period. Under the experimental conditions set in this study, the skin thickness of hairless mice significantly decreased (11.8-21.3%) compared to the control group. Based on these results, the prolonged oral intake of a collagen peptide mixture with coffee is expected to significantly increase the synthesis of procollagen in dermal fibroblasts, thereby contributing to the alleviation of wrinkling and lowered elasticity due to structural damage to the dermal layer caused by UV. The oral intake of collagen-coated coffee contributes to increasing collagen biosynthesis in a dose-dependent manner and alleviates the symptoms of thickened keratin caused by UV irradiation. However, it did not inhibit the enzymes involved in skin aging, whitening, wrinkle improvement, and antioxidation. Based on the these results, it can be concluded that the intake of collagen peptide-coated coffee extract can be utilized as an alternative material for the prevention or treatment of diseases associated with photoaging.