• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.103-103
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• 2018

Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.

• Korean Journal of Medicinal Crop Science
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• v.28 no.1
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• pp.9-20
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• 2020

Background: Although a number of Panax ginseng cultivars have been developed by Korean researchers in recent years, there has been insufficient analysis of their beneficial properties. In this study, we sought to identify useful ginseng varieties as functional materials. Methods and Results: We evaluated effects of root extracts of 10 ginseng cultivars (Cheongsun; CS, Chunpoong; CP, Gopoong; GP, Gumpoong; GMP, K1, Sunhyang; SH, Sunone; SO, Sunpoong; SP, Sunun; SU and Yunpoong; YP) against the inhibitory effects of nitric oxide (NO) and reactive oxygen species (ROS) production in mouse brain microglial BV2 cells, as well as the binding of N-methyl-D-aspartate receptor (NMDAR), a marker related to memory. Ginsenosides, such as 20 (S)-protopanaxadiols (PPDs), including ginsenoside-Rb1, -Rb2, -Rb3, -Rc, -Rd, and - Rg3 and 20 (S)-protopanaxatriols (PPTs) including -Re, -Rg1, and -Rg2 were analyzed by HPLC. We observed that the cultivar GMP showed the highest inhibitory effect (60.8%) against NO production at 20 ㎍/㎖. Those cultivars showing the significantly highest inhibition effects against ROS at 20 ㎍/㎖ were K1 (57.3%), SP (54.5%), YP (53.1%), CP (51.7%), CS (50.9%) and SH (49.6%). At 50 ㎍/㎖, K1 showed the most potent inhibitory effect (51.2%) on NMDAR binding. The total phenol content of SH (1.89 mg/g) and K1 (1.73 mg/g) were higher than those of the other cultivars, whereas in terms of PD/PT ratios, the values of CP (0.98), K1 (1.05) and SO (1.05) were lower than those of the other cultivars. On the basis of correlation coefficient (0.7064) between NMDAR inhibition and ONOO^- scavenging activity. Conclusions: The findings of this study indicate that the cultivars K1 and SH could be useful ginseng resources as functional materials with favorable cognition-improving and antioxidative properties.

• The Korea Journal of Herbology
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• v.30 no.4
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• pp.57-64
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• 2015

Objectives : Oxidative stress is one of the most causes of hepatocyte injury. Gleditsia spina, the thorns ofGleditsia sinensisLam., has been known for its anti-cancer and anti-inflammatory effects in Korean medicine. The present study investigated hepatoprotective effect of Gleditsia spina water extract (GSE) against oxidative stress induced by arachidonic acid (AA) + iron in HepG2 cells.Methods : To investigate cytoprotective effect of GSE, cells were pretreated with GSE and then subsequently exposed to 10 μM AA for 12 h, followed by 5 μM iron. Cell viability was monitored by MTT assay, and expression of apoptosis-related proteins was examined by immunoblot analysis. To identify responsible molecular mechanisms, reactive oxygen species (ROS) production, GSH contents, and mitochondrial membrane potential were measured. In addition, effect of GSE on nuclear factor erythroid 2-related factor 2 (Nrf2) activation was determined by immunoblot and antioxidant response element (ARE)-driven reporter gene assays.Results : GSE pretreatment prevented AA + iron-mediated cytotoxicity in concentration dependent manner. In addition, ROS production, glutathione depletion, and mitochondrial impairment by AA + iron were significantly inhibited by GSE. Furthermore, GSE promoted translocation of Nrf2 to nucleus, which acts as essential transcription factor for induction of antioxidant genes. Increased nuclear Nrf2 that caused by GSE treatment promoted transcriptional activity of ARE. Finally, GSE up-regulated sestrin-2 which was widely recognized as target gene of Nrf2.Conclusions : This study demonstrates that GSE protects hepatocytes from oxidative stress via activation of Nrf2 signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.541-549
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• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Environmental Mutagens and Carcinogens
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• v.25 no.2
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• pp.51-59
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• 2005

Overexpression of HSP25 delayed cell growth, increased the level of $p21^{waf}$, reduced the levels of cyclin D1, cylcin A and cdc2, and induced radioresistance in L929 cells. We demonstrated that extracellular regulated kinase (ERK) and MAP kinase/ERK kinase (MEK) expressions as well as their activation (phospho-forms) were inhibited by hsp25 overexpression. To confirm the relationship between ERK1/2 and hsp25-mediated radioresistance, ERK1 or ERK2 cDNA was transiently transfected into the hsp25 overexpressed cells and their radioresistance was examined. HSP25-mediated radioresistance was abolished by overexpression of ERK2, but not by overexpression of ERK1. Alteration of cell cycle distribution and cell cycle related protein expressions (cyclin D, cyclin A and cdc2) by hsp25 overexpression were also recovered by ERK2 cDNA transfection. Increase in Bc1-2 protein by hsp25 gene transfection was also reduced by subsequent ERK2 cDNA-transfection. In addition, HSP25 overexpression reduced reactive oxygen species (ROS) and increased expression of manganese superoxide dismutase (MnSOD) gene. Increased activation of NF-kB (IkB degradation) was also found in hsp25-overexpressed cells. Moreover, transfection of hsp25 antisense gene abrogated all the HSP25-mediated phenomena. To further elucidate the exact relationship between MnSOD induction and NF-kB activation, dominant negative $I-kB\alpha(I-kB\alpha-DN)$ construction was transfected to HSP25 overexpressed cells. $I-kB\alpha-DN$ inhibited HSP25 mediated MnSOD gene expression. In addition, HSP25 mediated radioresistance was blocked by $I-kB\alpha-DN$ transfection. Blockage of MnSOD with antisense oligonucleotides in HSP25 overexpressed cells, prevented apoptosis and returned the ERK1/2 activation to the control level. From the above results, we suggest for the first time that reduced oxidative damage by HSP25 was due to MnSOD-mediated down regulation of ERK1/2.

• Journal of Periodontal and Implant Science
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• v.44 no.2
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• pp.57-64
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• 2014

Purpose: Both chronic periodontitis (CP) and iron deficiency anemia (IDA) induce oxidative stress in the body and cause an imbalance between reactive oxygen species and antioxidants, such as superoxide dismutase (SOD). This study explored the SOD enzyme activity of saliva and serum in CP patients with and without IDA and analyzed the impact of IDA on CP. Methods: A total of 82 patients were divided into four groups: control group (CG, 22), periodontally healthy IDA patients (IDA-PH, 20), CP patients (CP, 20), and IDA patients with CP (IDA-CP, 20). After clinical measurements and samplings, serum and salivary SOD levels were determined using an SOD assay kit. Results: IDA-CP patients exhibited a higher gingival index, bleeding on probing, probing pocket depth, and percentage (%) of sites with a clinical attachment loss (CAL) of ${\geq}6mm$ (P<0.008) than CP patients. The mean salivary and serum SOD levels were significantly lower in the IDA-PH, CP, and IDA-CP patients than in the CG group (P<0.008). A significant positive correlation between salivary and serum SOD activity was observed in IDA (P<0.05). Furthermore, serum and salivary SOD levels were significantly and negatively correlated with all periodontal parameters including the percentage of sites with CAL of 4-5 and ${\geq}6mm$ (P<0.05) except the significant correlation between salivary SOD activity and mean CAL and the percentage of sites with CAL of 4-5 mm (P>0.05) in these patients. Conclusions: Within the limits of this study, it may be suggested that IDA patients with chronic periodontitis have more periodontal breakdowns than patients with chronic periodontitis. Serum and salivary SOD activity levels were lower in the IDA-PH, CP and IDA-CP groups than in the CG. Iron deficiency anemia influenced the serum SOD activity but did not seem to affect the salivary SOD activity in these patients.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.113-120
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• 2009

Background: Reactive oxygen species (ROS) by oxidative stress may play an important role in the pathogenesis of various chronic diseases such as diabetes mellitus, obesity, hyperlipidemia, hypertension and malignancy that are linked to metabolic syndrome. Oxidative stress has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We examined the relationship between IPF and presenting factors associated with metabolic disorders. Methods: One hundred fourteen patients who met the current consensus of IPF definition were enrolled from March 2000 to April 2006 in Gil Hospital and Samsung Medical Center in Korea. One hundred thirty-four control subjects without pulmonary diseases were selected from subjects who visited Gil hospital for routine medical examinations, including low-dose chest computed tomography from January 2002 to July 2006. Retrospectively, we analyzed the clinical characteristics, the results of blood examinations, and lung function tests from medical records of both groups. Results: IPF patients and control subjects differed in the prevalence of diabetes mellitus as assessed by univariate analysis. Multivariate analysis demonstrated that diabetes mellitus and obesity were associated with IPF. The adjusted odds ratios for diabetes mellitus were 2.733 (95% confidence interval [CI], 1.282~5.827) and 2.001 (95% [CI], 1.063~3.766) for obesity. The remaining factors tested showed no differences between the patient group and the control. Conclusion: Diabetes mellitus and obesity may be associated with IPF development.

• KSBB Journal
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• v.21 no.6 s.101
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• pp.444-450
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• 2006

Skin anti-aging effect of Forsythia viridissima L. extract was evaluated by using antioxidant assay, expression of type I procollagen, and UVA-induced matrix metalloproteinase-1 in human dermal fibroblasts. Matairesinol-rich Forsythia viridissima L. extract was showed the scavenging activity of radicals and reactive oxygen species with the $IC_{50}$ values of $4.50\;{\mu}m/ml$ against 1,1-diphenyl-2-picrylhydrazly radical and $542.43\;{mu}m/ml$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. The type I procollagen was increased 33.76% by treatment with matairesinol-rich Forsythia viridissima L. extract, and UVA-induced MMP-1 was reduced 35.78% in a dose dependent manner. In the human skin irritation test, 2% matairesinol-rich Forsythia viridissima L. extract did not show any adverse effect. Also, the clinical study indicated that a cream group treated with 0.2% matairesinol-rich Forsythia viridissima L. extract significantly reduced skin wrinkles, as compared with a non-treated cream group (p < 0.05). These results suggest that Forsythia viridissima L. extract may be useful as a potential source of functional anti-aging cosmetics.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.1
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• pp.21-28
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• 2017

Background: The skin consists of tightly connected keratinocytes, and prevents extensive water loss while simultaneously protecting against the entry of microbial pathogens. Excessive cellular levels of reactive oxygen species can induce cell apoptosis and also damage skin integrity. Propofol (2,6-diisopropylphenol) has antioxidant properties. In this study, we investigated how propofol influences intracellular autophagy and apoptotic cell death induced by oxidative stress in human keratinocytes. Method: The following groups were used for experimentation: control, cells were incubated under normoxia (5% $CO_2$, 21% $O_2$, and 74% $N_2$) without propofol; hydrogen peroxide ($H_2O_2$), cells were exposed to $H_2O_2$ ($300{\mu}M$) for 2 h; propofol preconditioning (PPC)/$H_2O_2$, cells pretreated with propofol ($100{\mu}M$) for 2 h were exposed to $H_2O_2$; and 3-methyladenine $(3-MA)/PPC/H_2O_2$, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to $H_2O_2$. Cell viability, apoptosis, and migration capability were evaluated. Relation to autophagy was detected by western blot analysis. Results: Cell viability decreased significantly in the $H_2O_2$ group compared to that in the control group and was improved by propofol preconditioning. Propofol preconditioning effectively decreased $H_2O_2$-induced cell apoptosis and increased cell migration. However, pretreatment with 3-MA inhibited the protective effect of propofol on cell apoptosis. Autophagy was activated in the $PPC/H_2O_2$ group compared to that in the $H_2O_2$ group as demonstrated by western blot analysis and autophagosome staining. Conclusion: The results suggest that propofol preconditioning induces an endogenous cellular protective effect in human keratinocytes against oxidative stress through the activation of signaling pathways related to autophagy.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.1
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• pp.37-46
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• 2017

Background: In oxidative stress, reactive oxygen species (ROS) production contributes to cellular dysfunction and initiates the apoptotic cascade. Autophagy is considered the mechanism that decreases ROS concentration and oxidative damage. Propofol shows antioxidant properties, but the mechanisms underlying the effect of propofol preconditioning (PPC) on oxidative injury remain unclear. Therefore, we investigated whether PPC protects against cell damage from hydrogen peroxide ($H_2O_2$)-induced oxidative stress and influences cellular autophagy. Method: COS-7 cells were randomly divided into the following groups: control, cells were incubated in normoxia (5% $CO_2$, 21% $O_2$, and 74% $N_2$) for 24 h without propofol; $H_2O_2$, cells were exposed to $H_2O_2$ ($400{\mu}M$) for 2 h; $PPC+H_2O_2$, cells pretreated with propofol were exposed to $H_2O_2$; and 3-methyladenine $(3-MA)+PPC+H_2O_2$, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to $H_2O_2$. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) reduction. Apoptosis was determined using Hoechst 33342 staining and fluorescence microscopy. The relationship between PPC and autophagy was detected using western blot analysis. Results: Cell viability decreased more significantly in the $H_2O_2$ group than in the control group, but it was improved by PPC ($100{\mu}M$). Pretreatment with propofol effectively decreased $H_2O_2$-induced COS-7 cell apoptosis. However, pretreatment with 3-MA inhibited the protective effect of propofol during apoptosis. Western blot analysis showed that the level of autophagy-related proteins was higher in the $PPC+H_2O_2$ group than that in the $H_2O_2$ group. Conclusion: PPC has a protective effect on $H_2O_2$-induced COS-7 cell apoptosis, which is mediated by autophagy activation.