• Journal of Life Science
• /
• v.24 no.9
• /
• pp.946-951
• /
• 2014

Melanin plays a key role in the protection of skin from ultraviolet light that generates reactive oxygen species (ROS), such as superoxide, hydroxyl radical, singlet oxygen and hydrogen peroxide. However, the ROS leading to the oxidation of lipids, proteins and DNA are involved in the overproduction of melanin that is known to cause melasma, age spots and freckles. Among the herb medicines, Ulmus macrocarpa used in this study was reported to contain flavonoids as a main component. The aim of this study is to investigate the whitening and anti-oxidant effects of Ulmus macrocarpa ethanolic extracts (UMEE) in B16F1 cells. UMEE below $3.12{\mu}g/ml$ did not show cytotoxicity. In an anti-oxidant experiment, UMEE showed not only high reducing power and scavenging activity on DPPH, but it was also observed that UMEE exhibit an inhibitory effect on lipid peroxidation. UMEE did not display an inhibitory effect on tyrosinase activity in vitro. However, UMEE inhibited melanin synthesis in B16F1 cells. In addition, UMEE reduced the expression levels of tyrosinase and tyrosinase-related protein-2 (TRP-2), which are key enzymes in melanogenesis. These results indicate that UMEE exert a whitening effect through the inhibition of both tyrosinase and TRP-2 expressions as well as anti-oxidant activity, suggesting that UMEE could have the functional potential for a whitening effect on the skin.

• Molecules and Cells
• /
• v.38 no.10
• /
• pp.886-894
• /
• 2015

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-$Gu{\acute{e}}rin$) activates disabled $na{\ddot{i}}ve$ macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). 1 The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-${\alpha}$), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-$1{\beta}$), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-${\beta}$) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.

• Molecules and Cells
• /
• v.40 no.8
• /
• pp.567-576
• /
• 2017

The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

• Korean Journal of Clinical Laboratory Science
• /
• v.42 no.3
• /
• pp.136-148
• /
• 2010

Cadmium (Cd) is known to exert gonadotoxic and spermiotoxic effects. The present study was performed to investigate the morphological effects and metallothionein (MT) expression by zinc pretreatment in the course of time of cadmium-induced testicular injury in rat. Fifty male Spraque-Dawley rats weighing 160-180 g were divided into two groups: saline-pretreated cadmium group and zinc-pretreated cadmium group. Rats of two groups received subcutaneous injection of saline and 100 mg/kg $ZnSO_4$ at 0, 2, 5 and 8 hrs intervals respectively. Cadmium chloride (4.5 mg/kg $CdCl_2$) was administrated intraperitoneally at 2 hr after zinc injection and rats were killed 0, 12, 24, 48 and 72 hrs later. Testicular tissue damages, Interstitial (Leydig) cells status and MT expression were determined using hematoxylin-eosin stained sections and a computerized image analysis system on sections immunostained with a mouse anti-metallothionein respectively. Zinc pretreatment was significantly reduced testicular damages in five pathological categories after cadmium administation. The number of surviving interstitial cells was significantly higher in the zinc-pretreated group than in the saline-preatreated group at 48 and 72 hrs after cadmium administration. Non-damaged testis showed the positivity of MT staining in spermatogenic cells, Sertoli cells and endothelium of blood vessel, but not in the Leydig cells. The potitivity of MT staining in saline-pretreated group was significantly reduced at 24 hrs after cadmium administration, whereas zinc-pretreated group showed strong MT positive staining similar to the 0 hr by 42 hrs after cadmium administration. In damaged testis, MT positive staining was also observed in the Leydig cells of both groups. These results suggest a major preventive effect of zinc against cadmium-induced testiculat toxicity may be due to its ability to reduce the cytotoxicity of cadmium in spermatogenic cells and Leydig cells by inhibiting the susceptibility of the testis to cadmium but not MT production by cadmium.

• Korean Journal of Medicinal Crop Science
• /
• v.17 no.6
• /
• pp.397-406
• /
• 2009

The low quality fresh ginseng was extracted by water at $80^{\circ}C$ and 240 bar for 20 min (HPE, High pressure extraction process). The cytotoxicity on human normal kidney cell (HEK293) and human normal lung cell (HEL299) of the extracts from HPE showed 28.43% and 21.78% lower than that from conventional water extraction at $100^{\circ}C$ in adding the maximum concentration of $1.0\;mg/m{\ell}$. The human breast carcinoma cell and lung adenocarcinoma cell growth were inhibited up to about 86%, in adding $1.0\;mg/m{\ell}$ of extracts from HPE. This values were 9-12% higher than those from conventional water extraction. On in vivo experiment using ICR mice, the variation of body weight of mice group treated fresh ginseng extracts from HPE of 100 mg/kg/day concentration was very lower than control and other group. The extracts from HPE was showed longer survival times as 35.65% than that of the control group, and showed the highest tumor inhibition activities compared with other group, which were 70.64% on Sarcoma-180 solid tumor cells. On the high performance liquid chromatogram (HPLC), amount of ginsenoside-$Rg_2$, $Rg_3$, $Rh_1$ and $Rh_2$ on fresh ginseng were increased up to 43-183% by HPE, compared with conventional water extracts. These data indicate that HPE definitely plays an important role in effectively extracting ginsenoside, which could result in improving anticancer activities. It can be concluded that low quality fresh ginseng associated with this process has more biologically compound and better anticancer activities than that from normal extraction process.

• Korean Journal of Medicinal Crop Science
• /
• v.15 no.6
• /
• pp.398-404
• /
• 2007

This study was performed to investigate the enhancement of anticancer activities and immuno modulatary activities from R. coreanus. by ultra high pressure extracts process. The cytotoxicity on human kidney cell (HEK293) was showed below 19.5% in adding 1.0 $mg/m{\ell}$ concentration. The anticancer activity was increased over 10% by high pressure processing in AGS and A549 cells. The immune cell growth using human immune B and T cells was improved by the high pressure extracts of Rubus coreanus in adding 1.0 $mg/m{\ell}$ concentration. The secretion of two kinds of cytokine, the IL-6 and $TNF-{\alpha}$ from human immune B and T cells were also enhanced in adding extracts by high pressure process of R. coreanus. The ultra high pressure extraction technique showed high efficiency in extracting of bioactive compound. The ultra high pressure technique could be used combined with other technique to improve the extracting rate and extracting efficiency.

• KSBB Journal
• /
• v.22 no.6
• /
• pp.414-420
• /
• 2007

Nanomaterials have been applied to various fields due to their advantageous characteristics such as high surface area, rapid diffusion, high specific surface areas, reactivity in liquid or gas phase, and a size close to biomacromolecules. Up to date, increased manufacturing and frequently use of the materials, however, revoke people's concerns on their hazard impact including toxicity the materials. Many research groups have carried out different protocols to evaluate toxic effects of nanomaterilas on different organisms, and consequently, nanomaterials are known to cytotoxicity. In this paper, we reviewed some of the most reports on toxic effects of several nanoparticles specifically on bacteria. There are numbers of reports focused on antibacterial effect of nanoparticles based on bacterial cell viability. Therefore, the application of each nanomaterial should be concerned with its toxicity and its toxic effect should be evaluated in terms of concentrations and sizes of the nanomaterials used, prior to use of a nanomaterial.

• Journal of Environmental Health Sciences
• /
• v.39 no.1
• /
• pp.48-55
• /
• 2013

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

• Journal of Korean Society of Forest Science
• /
• v.99 no.4
• /
• pp.470-478
• /
• 2010

UV-protection skin whitening and immune activities several parts of Acer mono and Acer okamotoanum were investigated. The bark of both Acer mono and Acer okamotoanum had higher yields than other parts as 2.67% and 2.45%. The cytotoxicity of the extracts were lower than 21.64% against human skin cell(CCD-986sk) line in adding 1.0 mg/mL of the highest concentration. The bark extracts of Acer mono greatly reduced the expression of MMP-1 on UV-irradiated CCD-986sk cells down to as 30%. At 1.0 mg/mL of bark extration of Acer mono, $PGE_2$ expression was also significantly decreased. Generally, the bark extracts of Acer mono and Acer okamotoanum had higher activity than other parts, but, interestingly, wood extract of Acer okamotoanum showed strong inhibition effect on melanin production by Clone-M3 cells as 79.25%. From these results, we could conclude that the bark extract from Acer mono and Acer okamotoanum had skin-whitening activity as well immune enhancement activity.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.45 no.11
• /
• pp.1595-1603
• /
• 2016

The present study examined the anti-inflammatory effects of Oenanthe javanica ethanol extract (OJE) and its fraction on the lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 macrophage cells. OJE remarkably reduced protein expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2), resulting in inhibition of production of nitric oxide (NO). In order to identify the anti-inflammatory effects of bioactive fractions, OJE was fractionated into hexane, dichloromethane, ethyl acetate, and n-butanol fractions. The results show that the ethyl acetate and dichloromethane fractions reduced production of NO without cytotoxicity. Especially, the ethyl acetate fraction effectively reduced protein expression of iNOS and COX-2. Proinflammatory cytokine production was also reduced by ethyl acetate fractions in LPS-induced RAW 264.7 cells. These data suggest that OJE and its fraction possess pharmacological activity and might be useful for development of anti-inflammatory agents or dietary supplements.