• Korean Journal of Food Science and Technology
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• v.40 no.6
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• pp.696-701
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• 2008

The objective of this study was to determine whether Codonopsis lanceolata or Platycodon grandiflorum ethyl acetate fraction (CLEA or PGEA) protect cells against sodium nitroprusside (SNP)-induced oxidative stress via the expression of various antioxidant systems. The HepG2 cells exposed for 24 hr to 0.5 mM SNP showed a reduction in the cell viability by an MTT assay. Pretreatment with CLEA and PGEA resulted in an inhibition of SNP-induced cell death. In addition, the effects of CLEA and PGEA on the expression of antioxidant systems via RT-PCR analyses was assessed. The levels of catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD) and metallothionein (MT)-1A mRNA were increased after 24 hr of CLEA exposure. The levels of Mn superoxide dismutase CAT, G6PD, MT-1A, and MT-2A mRNA were increased after PGEA treatment. In conclusion, CLEA and PGEA exert indirect antioxidant effects, perhaps via the induction of a variety of antioxidant systems which, may protect cells against oxidative stress.

• Molecules and Cells
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• v.38 no.4
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• pp.327-335
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• 2015

Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic ${\alpha},{\beta}$-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.

• Herbal Formula Science
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• v.23 no.2
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• pp.189-198
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• 2015

Objectives : Sparganii Rhizoma is frequently used in traditional herbal medicine for treatment of blood stasis, amenorrhea and functional dyspepsia and has been reported to exhibit anti-oxidant, anti-proliferation and anti-angiogenesis peoperties. In this study, we investigated the cytoprotective effect and underlying mechanism of Sparganii Rhizoma water extract (SRE) against oxidative stress-induced mitochondrial dysfunction and apoptosis in hepatocyte. Methods : To determine the effects of SRE on oxidative stress, we induced synergistic cytotoxicity by co-treatment of arachidonic acid (AA) and iron in the HepG2 cell, a human derived hepatocyte cell line. Results : Treatment of SRE increased relative cell viability and altered the expression levels of apoptosis-related proteins such as Bcl-xL, Bcl-2 and procaspase-3. And SRE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species production induced by AA+iron. In addition, SRE activated of AMP-activated protein kinase (AMPK), a potential target for cytoprotection, by increasing the phosphorylation of AMPKα at Thr-172. Morever, SRE increased phosphorylation of acetyl-CoA carboxylase, a direct downstream target of AMPK. Conclusion : These results indicated that SRE has the ability to protect against oxidative stress-induced hepatocyte damage, which may be mediated with AMPK pathway.

• Journal of Oral Medicine and Pain
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• v.37 no.2
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• pp.81-91
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• 2012

It has been known that saliva may affect the most of oral diseases. On the contrary, several systemic conditions may affect salivary flow and cause oral dryness and psychosocial stress especially may a crucial role in the etiology of hyposalivation and oral dryness. Many studies have focused on macroscopic effects of the stress on the salivary glands by autonomic respose, but on the other hand it has hardly been reported on cellular microscopic effects of the stress on the salivary glands. Therefore, this study was performed to examine clusterin, a antiapoptotic and cytoprotective protein, in the parotid glands under restraint stress condition. For this study, 10 rats were divided into 3 groups; 1) 2 rats of group I were selected as a normal control. 2) 2 rats of group II, as a experimental control were placed in the restraint cone for 2 hours 3) 6 rats of group III were placed in the restraint cone for 2 hours once a day. The rats were sacrificed immediately(group II, as a experimental control), 24, 48, and 72 hours after application of the stress and the parotid glands were excised. Western blotting and immunohistochemistry were performed. The finding were as follows: 1. In parotid glands, clusterin was mildly increased and clearly expressed in the ductal cell under restraint stress immediately after application of the stress. 2. In parotid glands, clusterin was significantly decreased and slightly stained in the ductal cell under restraint stress 24 and 48 hours after experiment. 3. In parotid glands, clusterin was prominently increased again and densely stained in the ductal cell under restraint stress 72 hours after experiment.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.247-251
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• 2004

UV radiation exerts various influences in the skin, including photoaging and inflammation (1). The MMPs (Matrix metalloproteinases), which are induced by UV irradiation, can degrade matrix proteins, and these results in a collagen deficiency in photodamaged skin that leads to skin wrinkling. It has been known that the production of PGE$_2$ stimulates MMPs expression, and inhibits procollagen (2). Thus, it is possible that the induction of MMPs and the inhibition of matrix protein synthesis by UV -induced PGE$_2$ may play some role in UV-induced collagen deficiency in photoaged skin. Fructose-1,6-diphosphate (FDP), a glycolytic metabolite, is reported to have cytoprotective effects against ischemia and postischemic reperfusion injury of brain and heart, presumably by augmenting anaerobic carbohydrate metabolism (3). And also, FDP significantly prevent skin aging by decreasing facial winkle compared with vehicle alone after 6 months of use. We studied the mechanism of anti-aging effect of FDP on UVB-irradiated HaCaT keratinocyte model. FDP has protective role in UVB injured keratinocyte by attenuating prostaglandin E$_2$ (PGE$_2$) production and COX-2 expression. And FDP also suppressed UVB-induced MMP-2 expression. Further, to delineate the inhibition of UVB-induced COX-2 and MMPs expression with cell signaling pathways, treatment of FDP to HaCaT keratinocytes resulted in marked inhibition of UVB-induced phosphorylation of ERK1/2, JNK. It also prevents UV induced NFB translocation, which are activated by cellular inflammatory signal. Our results indicate that FDP has protecting effects in UV-injured skin aging by decreasing UVB-induced COX-2 and MMPs expression, which are possibly through blocking UVB-induced signal cascades.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.3
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• pp.237-245
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• 2021

Particulate matter and ultra-particle matters generally refer to very small floating dust, such as 1/6 to 1/7 and 1/20 to 1/30, respectively, compared to the thickness of human hair, and contain various types of heavy metal ions. In addition to breathing, particle matters (PM) that flows in through the gaps in the pores of the skin can induce health problems in the body's tissues and skin, so it must be removed by blocking the inflow or by washing. Through this study, we confirmed the possibility that heavy metal ions can be adsorbed and removed by using Oryza sativa (Rice) bran oil (OSBO). In addition, the cell viability is much higher than that of grain-derived components through cytotoxicity experiments, and the cytoprotective effect of an external stimulus source can be expected. It was confirmed that the expression amount of COL1A1 mRNA increased, and accordingly, it was believed that wrinkles that might be caused by moisture lost by heavy metal ions in fine dust could be alleviated. Based on the results of these experiments, we tried to present a cosmetics containing OSBO, which is a wash-off formulation, in order to finally remove heavy metals.

• Journal of Life Science
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• v.32 no.2
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• pp.125-134
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• 2022

This study investigated whether or not the major bioactive compounds of Noni (Morinda citrifolia) are involved in anti-inflammatory activity through the JAK/STAT upper signaling pathway in RAW 264.7 cells. The experimental results show that the M. citrifolia ethyl acetate fraction (Mc-EtOAc) obtained by sequential fractionation with organic solvents from the plant's dried fruits exhibits the highest antioxidant activity. In addition, the cytoprotective effects of Mc-EtOAc against H₂O₂-induced oxidative stress in the RAW 264.7 cells suppressed cytotoxicity in a dose-dependent manner. The group pretreated with Mc-EtOAc at a concentration of 240 ㎍/ml showed higher cell viability of 84.5%, compared to 71.6% in the LPS-treated group, and LPS-induced NO production decreased to half the amount in the positive control group. Mc-EtOAc treatment also led to a significant dose-dependent reduction in iNOS expression. Although COX-2 expression was increased by 300% following LPS induction, it was significantly decreased in a dose-dependent manner by pretreatment with Mc-EtOAc at concentrations of 120 and 240 ㎍/ml. An inhibition of the mRNA expression of pro-inflammatory cytokines IL-1β and TNF-α was observed. The investigation also revealed that the phosphorylation levels of pJAK1 and pSTAT3 in LPS-induced RAW 264.7 cells were significantly reduced by Mc-EtOAc treatment.

• Herbal Formula Science
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• v.31 no.4
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• pp.231-243
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• 2023

Objectives : Jasminum officinale L. var. grandiflorum is used as a traditional or folk remedy in China to treat arthritis, hepatitis, duodenitis, conjunctivitis, gastritis, and diarrhea. In this study, we aimed to study the hepatocyte protective activity and molecular mechanism of Jasminum officinale L. var. grandiflorum aqueous extract (JGW) using HepG2 hepatocyte cell lines. Methods : HepG2 cells were pretreated with diverse concentrations of JGW, and then the cells were exposed to tert-butyl hydroperoxide (tBHP) for inducing oxidative stress. Hydrogen peroxide (H₂O₂) production, glutathione (GSH) concentration, mitochondrial membrane potential (MMP) and cell viability were measured to investigate hepato-protective effects of JGW. Phosphorylation of AMP-activated protein kinases (AMPK), acetyl coenzyme A carboxylase (ACC) and effects of compound C on cell viability were examined to observe the role of AMPK on JGW-mediated cytoprotection. Results : Pretreatment with JGW (10-300 ㎍/mL) significantly suppressed cytotoxicity induced by tBHP in a concentration dependent manner and reduced the expression of cleaved PARP and cleaved caspase-3 proteins related to apoptosis in HepG2 cells. In addition, pretreatment with JGW significantly prevented the increase in H₂O₂ production, GSH depletion, and lower MMP induced by tBHP. Treatment with JGW (30 minutes of incubation and concentrations of 100 and 300 ㎍/mL) increased the phosphorylation of AMPK and ACC and treatment with compound C, a chemical inhibitor of AMPK, inhibited the cytoprotective effect of JGW. Conclusions : Our results demonstrated that JGW may protect hepatocytes from oxidative stress via activation of AMPK.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.481-489
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• 2005

Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

• Korean Journal of Food Science and Technology
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• v.46 no.3
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• pp.384-389
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• 2014

The objective of the present study was to investigate the chemical composition of anthocyanin-enriched extract of radiation-induced blackberry (Rubus fruticosus L.) mutant (${\gamma}$-B201) as well as the protective effect of ${\gamma}$-B201 against oxidative stress in vitro. The cytotoxicity, reactive oxygen species (ROS) scavenging capacity, and DNA damage were assessed by WST-1 assay, flow cytometry, and comet assay, respectively. Lactate dehydrogenase, superoxide dismutase, and catalase activities were determined by using a commercial kit. The in vitro results showed that ${\gamma}$-B201 increased the cell viability, reduction of lactate dehydrogenase release, and intracellular ROS scavenging capacity in hydrogen peroxide ($H_2O_2$)-treated HepG2 cells. Furthermore, treatment with ${\gamma}$-B201 attenuated DNA damage in $H_2O_2$-treated HepG2 cells and treatment with ${\gamma}$-B201 restored the activity of superoxide dismutase and catalase in $H_2O_2$-treated HepG2 cells. In conclusion, the present study suggests that ${\gamma}$-B201 blackberry extract can exert a significant cytoprotective effect against $H_2O_2$-induced cell damage.