• Biomolecules & Therapeutics
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• 제25권3호
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• pp.308-314
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• 2017

Urotensin II (UII) is a mitogenic and hypertrophic agent that can induce the proliferation of vascular cells. UII inhibition has been considered as beneficial strategy for atherosclerosis and restenosis. However, currently there is no therapeutics clinically available for atherosclerosis or restenosis. In this study, we evaluated the effects of a newly synthesized UII receptor (UT) antagonist, KR-36996, on the proliferation of SMCs in vitro and neointima formation in vivo in comparison with GSK-1440115, a known potent UT antagonist. In primary human aortic SMCs (HASMCs), UII (50 nM) induced proliferation was significantly inhibited by KR-36996 at 1, 10, and 100 nM which showed greater potency ($IC_{50}$: 3.5 nM) than GSK-1440115 ($IC_{50}$: 82.3 nM). UII-induced proliferation of HASMC cells was inhibited by U0126, an ERK1/2 inhibitor, but not by SP600125 (inhibitor of JNK) or SB202190 (inhibitor of p38 MAPK). UII increased the phosphorylation level of ERK1/2. Such increase was significantly inhibited by KR-36996. UII-induced proliferation was also inhibited by trolox, a scavenger for reactive oxygen species (ROS). UII-induced ROS generation was also decreased by KR-36996 treatment. In a carotid artery ligation mouse model, intimal thickening was dramatically suppressed by oral treatment with KR-36996 (30 mg/kg) which showed better efficacy than GSK-1440115. These results suggest that KR-36996 is a better candidate than GSK-1440115 in preventing vascular proliferation in the pathogenesis of atherosclerosis and restenosis.

• Molecules and Cells
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• 제21권1호
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• pp.121-128
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• 2006

Maitotoxin (MTX) is known as one of the most potent marine toxins involved in Ciguatera poisoning, but intracellular signaling pathways caused by MTX was not fully understood. Thus, we have investigated whether intracellular reactive oxygen species (ROS) are involved in MTX-induced cellular responses in human umbilical vein endothelial cells. MTX induced a dose-dependent increase of intracellular [$Ca^{2+}$]. MTX stimulated the production of intracellular ROS in a dose- and time-dependent manner, which was suppressed by BAPTA-AM, an intracellular $Ca^{2+}$ chelator. Ionomycin also elevated the ROS production in a dose-dependent manner. MTX elevated transamidation activity in a time-dependent manner and the activation was largely inhibited by transfection of tissue transglutaminase siRNA. The activation of tissue transglutaminase and ERK1/2 by MTX was suppressed by BAPTA-AM or ROS scavengers. In addition, MTX-induced cell death was significantly delayed by BAPTA-AM or a ROS scavenger. These results suggest that [$Ca^{2+}$]-dependent generation of intracellular ROS, at least in part, play an important role in MTX-stimulated cellular responses, such as activation of tTGase, ERK phosphorylation, and induction of cell death, in human umbilical vein endothelial cells.

• Archives of Reconstructive Microsurgery
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• 제14권2호
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• pp.85-94
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• 2005

Purpose: This study was to evaluate the effect of ${\alpha}-lipoic$ acid, a potent free radical scavenger, on the expression of active form of extracellular signal-regulated kinase (pERK1/2) proteins from hindlimb muscles of rats following ischemia-reperfusion injury. Material and methods: 64 health, $280{\sim}350\;g$ weighted Sprague-Dawley male rats were used. In order to make a muscle flap, the gastrocnemius (GC) and soleus (SOL) muscles were dissected and elevated. The popliteal artery was occluded for 4hours and reperfused for 10 minutes, 30 minutes, 1 hour, 2 hours and 4 hours, respectively. Results: The ischemia by occlusion of the popliteal artery itself caused a minimal change in expression of phosphorylated form of proteins observed in hindlimb muscle. In contrast, after 4 hours of ischemia, immunoreactivity for pERK1/2 in the GC muscle showed dual peaks at 10 minutes and 4 hours after reperfusion. In ${\alpha}-lipoic$ acid treated group, the expression of pERK1/2 was increased significantly compared to I/R-only group. Conclusion: These results suggest that ${\alpha}-lipoic$ acid may protect I/R injury of the skeletal muscle through free radical scavening and activation of intracellular pERK1/2 expression.

• 한국식품조리과학회지
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• 제25권4호
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• pp.406-414
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• 2009

This study was conducted to investigate the functional composition and antioxidant activity of Cirsium and Carduus genera based on different parts. Leaves of Cirsium setidens Nakai contained 23.66% protein and seeds of Carduus crispus L contained 25.30% lipid. Extraction yields of Cirsium and Carduus genera were higher in leaves than in any other parts of the plants. Total phenolics and total flavonoid content were abundant in extracts of leaves, steam and root of C. japonicum var. ussuriense, and the flower extract of C. setidens Nakai. Silymarin was not found in extracts of Cirsium and Carduus genera. Acacetin was identified in leaf or flower extracts of C. setidens Nakai, or in leaf and steam extracts of C. pendulum Fisch ex DC. Apigenin was identified in the flower extracts of Cirsium and Carduus genera and constituted 7.16 mg/g in C. japonicum var. ussuriense. Cynarin was present at 5.55 mg/g in the seed extract of C. setidens Nakai, and narirutin represented 19.56 mg/g and, 4.18 mg/g of the seed extracts of C. pendulum Fisch ex DC and, Carduus crispus L, respectively. 2,2-Diphenyl-1-2-picrylhydrazyl (DPPH) radical scavenger activity was higher in flower extracts of C. setidens Nakai than in the other genera. Photochemiluminescence activity was 2.3 nmol in leaves and flower extracts of C. setidens Nakai and flower extract of Carduus crispus L. Flowers and seeds of C. setidens Nakai shoe potential as new functional materials.

• Food Science and Biotechnology
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• 제15권3호
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• pp.437-440
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• 2006

To explore the possible usefulness of ${\beta}$-glucans as natural antioxidants, the antioxidant profiles of ${\beta}$-glucan, extracted from Saccharomyces cerevisiae KCTC 7911, and water soluble and insoluble mutant ${\beta}$-glucan, isolated from yeast mutant S. cerevisiae IS2, were examined by five different in vitro evaluation methods: lipid peroxidation value (POV), nitric oxide (NO), 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, reducing power, and ${\beta}$-carotene diffusion assay. The antioxidant activities of all ${\beta}$-glucans evaluated in POV test were comparable to or better than that of the known antioxidant, vitamin C. Remarkably, the ${\beta}$-glucan and water insoluble mutant ${\beta}$-glucan possessed 2.5-fold more potent activity than vitamin C at a dosage of 2 mg. Although vitamin C showed 100-fold greater activity than all ${\beta}$-glucans in NO and DPPH tests for measuring the radical scavenging capacity, all ${\beta}$-glucans revealed higher radical scavenging activity than the known radical scavenger, N-acetyl-L-cysteine (NAC), in DPPH test. The water insoluble mutant ${\beta}$-glucan had 2.6- and 5-fold greater antioxidative activity than water soluble ${\beta}$-glucan in NO and DPPH tests, respectively, showing that all ${\beta}$-glucans were able to scavenge radicals such as NO or DPPH. While all ${\beta}$-glucans revealed lower antioxidant profiles than vitamin C in both reducing power activity and ${\beta}$-carotene agar diffusion assay, the ${\beta}$-glucan and water insoluble mutant ${\beta}$-glucan did show a marginal reducing power activity as well as a considerable ${\beta}$-carotene agar diffusion activity. These results confirmed the potential usefulness of these ${\beta}$-glucans as natural antioxidants.

• Food Science and Biotechnology
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• 제14권3호
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• pp.399-404
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• 2005

The aim of this study was to investigate the in vitro antioxidant profiles of genistein and other isoflavonoids. The reactivity of genistein towards stable radical and reactive oxygen species including ${\bullet}\;ABTS^+$, ${\bullet}{O_2}^-$, $H_2O_2$ and HOCl has been investigated, and the effects were compared with other isoflavonoids and antioxidants. All the tested isoflavonoids showed remarkable ${\bullet}\;ABTS^+$ scavenging activity and genistein was more potent than BHT and ascorbic acid. Genistein was more effective in scavenging hypochlorous acid than superoxide and hydrogen peroxide. At $10\;{\mu}M$ concentrations of genistein and genistin showed about 90% inhibitory effect on HOCl, while BHT and ascorbic acid showed lower than 50% inhibitory effect. Moreover, genistein could inhibit plasmid DNA cleavage, protein degradation and cell death from HOCl attack, while daidzein, BHT and ascorbic acid could not protect them effectively. These results suggest that genistein is a more potent radical scavenger than other isoflavonoids, and it can remarkably reduce cellular damage induced by HOCl.

• Nutritional Sciences
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• 제9권1호
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• pp.14-19
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• 2006

Breast cancer may be the consequence of free radical damage, which is partially caused by the excessive intake of dietary fat and imbalances in antioxidant scavenger system;. In this experiment, we examined! the effects of dietary peroxidizability index (PI) values on hepatic thiobmbituric acid reaction substances (TBARS) and antioxidant enzyme activities in rats treated with 7,12-dimethylbenz[$\alpha$]anthracene (DMBA). Female Sprague-Dawley rats were used and 7,12-DMBA (20 mg/kg body weight) was gastrically intubated at seven weeks of age in order to induce mammary tumors (MT). The levels of dietary PI were 36, 81, 126 and 217 (LPI, MLPI, MHPI and HPI), while dietary polyunsaturated/saturated fatty acids ratio was maintained at the same level (1.0). Fat used in the experiment was mixed with soybean oil, com oil, palm oil, perilla oil, sesame oil, fish oil, and beef tallow. Experimental diets were given for the following 20 weeks. We measured tumor numbers and weights, and then assayed the hepatic TBARS levels and antioxidant enzyme activities such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione-S-transferase (GST) and glutathione reductase (GR). The incidence of Mr was the lowest in the MHPI group. The hepatic TBARS level was significantly raised with increasing dietary PI value. The hepatic SOD and GR activities were differed significantly by dietary PI value. The hepatic SOD activity was negatively correlated with dietary PI value and GR activity was the highest in the rats fed the MHPI diet. When the dietary P/S ratio is kept at 1.0, adequate dietary PI value (PI value of 126) may reduce the incidence and growth of Mr, but this benefit may be lost with higher dietary PI value. These results suggest that the awareness of dietary PI values may help to decrease breast cancer incidence and growth.

• Bulletin of the Korean Chemical Society
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• 제19권6호
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• pp.671-676
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• 1998

The formation and dissociation rates of $Ce^{3+}$ Complexes of the 1,4,7,10-tetraaza-13,16-dioxacyclooctadecane-NN', N",N"'-tetraacetic acid (1), 1,4,7,10-tetraaza-13,16-dioxacyclooctadecane-N,N',N",N"'-tetramethylacetic acid (2), and 1,4,7,10-tetraaza-13,16-dioxacyclooctadecane-N,N',N",N"'-tetrapropionic acid (3) have been measured by the use of stopped-flow spectrophotometry. Observations were made at 25.0±0.1 ℃ and at an ionic strength of 0.10 M $NaClO_4$. The complexation of $Ce^{3+}$ ion with 1 and 2 proceeds through the formation of an intermediate complex $(CeH_3L^{2+})^*$ in which the $Ce^{3+}$ ion is incompletely coordinated. This may then lead to be a final product in the rate-determining step. Between pH 4.76 and 5.76, the diprotonated $(H_2L^{2-})$ from is revealed to be a kinetically active species despite of its low concentration. The stability constants $(logK(CeH_3L^{2+}))$ and specific water-assisted rate constants $(k_{OH})$ of intermediate complexes have been determined from the kinetic data. The dissociation reactions of $Ce^{3+}$ complexes of 1, 2, and 3 were investigated with $Cu^{2+}$, ions as a scavenger in acetate buffer. All complexes exhibit acid-independent and acid-catalyzed contributions. The effect of buffer and $Cu^{2+}$ concentration on the dissociation rate has also been investigated. The ligand effect on the dissociation rate of $Ce^{3+}$ complexes is discussed in terms of the side-pendant arms and the chelate ring sizes of the ligands.

• Journal of Korean Neurosurgical Society
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• 제64권6호
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• pp.873-881
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• 2021

Objective : Peripheral nerve injuries occur mostly as a result of mechanical trauma. Due to the microvascular deterioration in peripheral nerve damage, it becomes challenging to remove free oxygen radicals. Gallic acid is a powerful antioxidant with anti-inflammatory effects and a free radical scavenger. The purpose of the study is to show that gallic acid contributes to the restorative effect in mechanical nerve damage, considering its antioxidant and anti-inflammatory effects. Methods : Thirty male Sprague Dawley albino mature rats were included in the study. Ten of them constituted the control group, 10 out of 20 rats for which sciatic nerve damage was caused, constituted the saline group, and 10 formed the gallic acid group. Post-treatment motor functions, histological, immunohistochemical, and biochemical parameters of the rats were evaluated. Results : Compared to the surgery+saline group, lower compound muscle action potential (CMAP) latency, higher CMAP amplitude, and higher inclined plane test values were found in the surgery+gallic acid group. Similarly, a higher nerve growth factor (NGF) percentage, a higher number of axons, and a lower percentage of fibrosis scores were observed in the surgery+gallic acid group. Finally, lower tissue malondialdehyde (MDA) and higher heat shock protein-70 (HSP-70) values were determined in the surgery+gallic acid group. Conclusion : Gallic acid positively affects peripheral nerve injury healing due to its anti-inflammatory and antioxidant effects. It has been thought that gallic acid can be used as a supportive treatment in peripheral nerve damage.

• Molecules and Cells
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• 제42권3호
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• pp.252-261
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• 2019

The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.