• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.101-110
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• 2018

In this study, we aimed to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE), an active component of propolis purified from honeybee hives, on photothrombotic cortical ischemic injury in mice. Permanent focal ischemia was achieved in the medial frontal and somatosensory cortices of anesthetized male C57BL/6 mice by irradiation of the skull with cold light laser in combination with systemic administration of rose bengal. The animals were treated with CAPE (0.5-5 mg/kg, i.p.) twice 1 and 6 h after ischemic insult. CAPE significantly reduced the infarct size as well as the expression of tumor necrosis $factor-{\alpha}$, hypoxiainducible $factor-1{\alpha}$ monocyte chemoattractant protein-1, $interleukin-1{\alpha}$, and indoleamine 2,3-dioxygenase in the cerebral cortex ipsilateral to the photothrombosis. Moreover, it induced an increase in heme oxygenase-1 immunoreactivity and interleukin-10 expression. These results suggest that CAPE exerts a remarkable neuroprotective effect on ischemic brain injury via its anti-inflammatory properties, thereby providing a benefit to the therapy of cerebral infarction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1027-1031
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• 2005

In the present study, wogonin, a major flavone isolated from Scutellaria Radix were examined for its imunosuppressive activity on the 2,4-dinitro-fluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) in C3H/HeN mice. This compound inhibited selectively $TNF-\alpha$ and IL-4, but not IL-6, IL-10 and $IFN-\gamma$ on DNFB-induced Th1 and Th2 cytokines in a concentration-dependent manner. Interestingly, this compound increased the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner The above results reveal that wogonin possesses anti-inflammatory, humoral and cellular immunomodulatory, and stress reducing activities on the DNFB-induced DTH in mice and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.2
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• pp.115-122
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• 2011

The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-${\alpha}$, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.306-311
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• 2008

Although hepatic microcirculatory dysfunction occurs during endotoxemia, the mechanism responsible for this remains unclear. Since Kupffer cells provide signals that regulate hepatic response in inflammation, this study was designed to investigate the role of Kupffer cells in the imbalance in the expression of vasoactive mediators. Endotoxemia was induced by intraperitoneal E. coli endotoxin (LPS, 1 mg/kg body weight). Kupffer cells were inactivated with gadolinium chloride ($GdCl_3$, 7.5 mg/kg body weight, intravenously) 2 days prior to LPS exposure. Liver samples were taken 6 h following LPS exposure for RT-PCR analysis of mRNA for genes of interest: endothelin (ET-1), its receptors $ET_A$ and $ET_B$, inducible nitric oxide synthase (iNOS), heme oxygenase (HO-1), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). mRNA levels for iNOS and TNF-$\alpha$ were significantly increased 31.8-fold and 26.7-fold in LPS-treated animals, respectively. This increase was markedly attenuated by $GdCl_3$, HO-1 expression significantly increased in LPS-treated animals, with no significant difference between saline and $GdCl_3$ groups. ET-1 was increased by LPS. mRNA levels for $ET_A$ receptor showed no change, whereas $ET_B$ transcripts increased in LPS-treated animals. The increase in $ET_B$ transcripts was potentiated by $GdCl_3$. We conclude that activation of Kupffer cells plays an important role in the imbalanced hepatic vasoregulatory gene expression induced by endotoxin.

• Environmental Analysis Health and Toxicology
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• v.25 no.2
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• pp.99-109
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• 2010

The distribution of ambient air particles varies according to climate, industries, and other sources. In this study, ambient air particles (less than 12.1 ${\mu}m$) were monitored from February to August, 2007 as 12 different fractions sorted by a cascade impactor. Particles in the size range from 0.33 ${\mu}m$ to 0.76 ${\mu}m$ comprised the main fraction of ambient air particles in Seoul, Korea. On the day of an Asian dust event, the particle fraction size increased to 1.25~2.5 ${\mu}m$. The different sized particle fractions were also monitored for metals and were found to contain toxic heavy metals including Pb, Cd, Hg, Cr and As. Particle preparations were significantly cytotoxic when exposed to cultured BEAS-2B cells. Microarray analysis of the treated cells indicated a significant up-regulation of a number of genes associated with oxidative stress, including metallothionein, heme oxygenase-1, heat shock protein 70, and NAD(P)H dehydrogenase-1.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.641-645
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• 2007

Delphinidin, an aglycone form of anthocyanins, was demonstrated to have anti-carcinogenic potential. The compound at $50\;{\mu}g/mL$ caused a significant increase of quinone reductase activity, an anti-carcinogenic marker enzyme, in mouse hepatoma cell lines (Hepa1c1c7 and BPRc1). Delphinidin enhanced the expression of other detoxifying or antioxidant enzymes including glutathione s-transferase, gamma-glutamylcysteine synthetase, heme oxygenase 1, and glutathione reductase. It suppressed the proliferation of murine hepatoma cells in a dose-dependent manner, with approximately $IC_{50}$ of $70\;{\mu}g/mL$. These results suggest that delphinidin might be useful for cancer prevention.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.83-93
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• 2015

Objectives : The purpose of this study was to evaluate whether acupuncture at $SP_6$ attenuates esophageal inflammation on refluxed-induced esophagitis. Methods : Acupuncture at $SP_6$ was stimulated by acupuncture torsion technique for 30 seconds four times every hour after an operation induced reflux esophagitis(RE), and its effects were assessed in comparison with RE rats without acupuncture, and normal rats. Results : $SP_6$ acupuncture stimulation markedly ameliorated mucosal damage in the histological evaluation. Reflux-induced esophagitis rats exhibited the down-regulation of antioxidant-related protein expression levels such as heme oxygenase-1(HO-1) in the esophagitis; however, the associated levels with $SP_6$ acupuncture stimulation were significantly higher than those in RE rats without acupuncture stimulation. Moreover, $SP_6$ acupuncture stimulation significantly reduced the expression of inflammatory proteins through mitogen-activated protein kinase(MAPK)-related signaling pathways. The increased protein expressions of inflammatory mediators, cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS), by nuclear factor-kappa B(NF-kB) activation were significantly suppressed through $SP_6$ acupuncture stimulation. Conclusions : Our findings support the therapeutic evidence for $SP_6$ acupuncture stimulation alleviating the development of esophagitis via regulating inflammation through the activation of the antioxidant pathway.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.75-84
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• 2016

This study was designed to investigate the cytoprotective effect of rosmarinic acid (RA) on ultraviolet B (UVB)-induced oxidative stress in HaCaT keratinocytes. RA exerted a significant cytoprotective effect by scavenging intracellular ROS induced by UVB. RA also attenuated UVB-induced oxidative macromolecular damage, including protein carbonyl content, DNA strand breaks, and the level of 8-isoprostane. Furthermore, RA increased the expression and activity of superoxide dismutase, catalase, heme oxygenase-1, and their transcription factor Nrf2, which are decreased by UVB radiation. Collectively, these data indicate that RA can provide substantial cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and has potential to be developed as a medical agent for ROS-induced skin diseases.

• Environmental Analysis Health and Toxicology
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• v.21 no.4 s.55
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• pp.357-363
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• 2006

Chromium compounds are widely used in diverse industries including pigment manufacturing, painting, metal plating and leather tanning. With the wide uses of chromium, various adverse effects of the compounds on the environment and human health have been reported. Among them, hexavalent chromium [Cr (VI)], which is a carcinogenic heavy metal, has been widely studies. Epidemiological investigations have shown that respiratory cancers had been found in workers who had been occupationally exposed to Cr (VI). In this study, cell toxicity and induction of reactive oxygen species (ROS) by Cr (VI) (1, 2, 4, $8{\mu}M$) in cultured human bronchial epithelial cells were investigated. Exposure of the cells to Cr (VI) led to cell death, ROS increase, and cytosolic caspase-3 activation. The ROS increase was related with the decreased level of GSH. Chromatin condensation and fragmentation were occurred by Cr (VI) when evaluated by DAPI staining or agarose gel electrophoresis of the extracted DNA. Expression of ROS related genes including glutathione S-transferase, heme oxygenase-1, metallothionein were significantly induced in Cr (VI) treated cells. This result suggests the toxicity in cultured cells by Cr (VI) was expressed through the apoptotic process with ROS induction.

• YAKHAK HOEJI
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• v.56 no.4
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• pp.260-267
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• 2012

This study examined the effects of baicalin, a bioactive flavonoid isolated from Scutellaria baicalensis, on hepatic injury caused by ischemia/reperfusion (I/R) in alcoholic fatty liver. Rats were fed an ethanol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was administered intraperitoneally 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increase in serum alanine aminotransferase activity. The levels of cytosolic cytochrome c protein expression, caspase-3 activity, the number of apoptotic cells increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. Following I/R, the hepatic lipid peroxidation was elevated, whereas hepatic glutathione content was decreased. These changes attenuated by baicalin. In ethanol-fed animals, baicalin augmented the increases in heme oxygenase-1 protein and mRNA expressions, and nuclear Nrf2 expression. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing apoptosis and oxidative stress in alcoholic fatty liver.