• Archives of Pharmacal Research
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• v.29 no.10
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• pp.849-858
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• 2006

Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The antiinflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl-methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.141-153
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• 2007

Objectives: The purpose of this report is to examine the effect of $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and LIl ${\cdot}$ $GB_{44}$ draining in acupuncture for cerebral apoplexy treatment. Methods : I designed to investigate whether $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture affects cerebral hemodynamics [regional cerebral blood flow(rCBF), mean arterial blood pressure(MABP)] in normal rats, and to make manifest whether $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture is mediated by cyclooxygenase or guanylate cyclase. The changes of rCBF and MABP were determinated by laser-doppler flowmetry(LDF). Results : 1. $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and LI1 ${\cdot}$ $GB_{44}$ draining in acupuncture increased rCBF significantly, but decreased MABP. These results suggest that $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture increased significantly rCBF by dilating pial arterial diameter(PAD). 2. By pretreatment with indomethacin(1 mg/kg, i.p.), the effect of $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture induced increase of rCBF was significantly inhibited, the decreased MABP by treatment with $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture was increased. 3. By pretreatment with methylene blue($10{\mu}/kg$, i.p.), the increased rCBF by treatment with $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture was decreased conversely, the decreased MABP by treatment with $BL_{66}$ ${\cdot}$ $GB_{43}$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture was decreased. and then increased. Conclusion : I suggest that $BL_{66}$ ${\cdot}$ $GB_43$ supplement and $LI_1$ ${\cdot}$ $GB_{44}$ draining in acupuncture has an anti-ischemic effect through the improvement of cerebral hemodynamics.

• The Korea Journal of Herbology
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• v.30 no.6
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• pp.63-68
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• 2015

Objectives : Gastric lesions affect many people around the world and their development are results of the imbalance between destructive and protective factors in the gastric mucosa. Lycium chinense has been widely used as a traditional Korean medicine, it was recently reported that they have potent anti-inflammatory effects in chronic hepatitis models. Therefore, this study aimed to investigate the anti-inflammatory activity of Lycium chinense extract (LCE) on HCl-Ethanol induced gastric lesion mice.Methods : The ICR mice were divided randomly into five groups of six animals each. Group A was normal mice, and group B was treated orally with 0.5 ml 150 mM HCl-60% Ethanol. Mice in group C and D were pre-treatment of LCE (100 mg/kg and 200 mg/kg bodyweight, p.o before HCl/ethanol treatment) and group E was orally administered sucralfate (10 mg/kg).Results : 150mM HCl/60% ethanol-induced gastric mucosal injury mice were ameliorated mucosal damage upon histological evaluation by treatment of LCE. Pre-treatment of LCE attenuated reactive oxidative species (ROS) and produces peroxynitrite (ONOO^-) in stomach tissues. As results of stomach protein analyses, LCE effectively reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) in gastric lesion mice. In addition, nuclear factor kappa B (NF-κB) and inhibitor of phosphorylation of nuclear factor kappa B (p-IκB) were down-regulated in LCE-administrated gastric lesion mice.Conclusions : Our discovery supports that the therapeutic activity of LCE ameliorate the development of gastric lesion via suppressing the oxidative stress and gastric partial inflammation induced by 150 mM HCl/60% ethanol.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.113-113
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• 2019

Diallyl trisulfide (DATS) is an organic polysulfide compound found in garlic. Although certain studies have demonstrated that DATS possesses strong anti-inflammatory activity, the underlying molecular mechanisms remain largely unresolved. In this study, we examined whether DATS exerts anti-inflammatory activity and investigated the possible mechanisms. Our results indicated that DATS significantly suppressed the lipopolysaccharide (LPS)-induced release of nitric oxide (NO) and prostaglandin E2 by inhibiting inducible NO synthase and cyclooxygenase-2 expression at the transcriptional and post-transcriptional levels in RAW 264.7 macrophages. DATS also down-regulated Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 expression, and inhibited nuclear translocation of nuclear transcription factor-kappa B (NF-${\kappa}B$) in LPS-stimulated 264.7 macrophages. Furthermore, we found that these inhibitory effects of DATS were associated with the inhibition of chemokine receptor (CXCR4) and ligand (CXCL12) expression, and reactive oxygen species generation. Overall, the present data indicated that DATS had anti-inflammatory effects on LPS-activated macrophages, possibly via inhibiting the TLR4/NF-kB and/or chemokine signaling pathways, and DATS could be a potential drug therapy for inflammation and its associated diseases.

• Journal of Microbiology and Biotechnology
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• v.31 no.11
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• pp.1501-1507
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• 2021

Lagerstroemia ovalifolia Teijsm. & Binn. (LO) (crape myrtle) has reportedly been used as traditional herbal medicine (THM) in Java, Indonesia. Our previous study revealed that the LO leaf extract (LOLE) exerted anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Based on this finding, the current study aimed to evaluate the protective effects of LOLE in a mouse model of LPS-induced acute lung injury (ALI). The results showed that treatment with LPS enhanced the inflammatory cell influx into the lungs and increased the number of macrophages and the secretion of the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of mice. However, these effects were notably abrogated with LOLE pretreatment. Furthermore, the increase of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression in the lung tissues of mice with ALI was also reversed by LOLE. In addition, LOLE significantly suppressed the LPS-induced activation of the MAPK/NF-κB signaling pathway and led to heme oxygenase-1 (HO-1) induction in the lungs. Additionally, in vitro experiments showed that LOLE enhanced the expression of HO-1 in RAW264.7 macrophages. The aforementioned findings collectively indicate that LOLE exerts an ameliorative effect on inflammatory response in the airway of ALI mice.

• The Korea Journal of Herbology
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• v.34 no.4
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• pp.27-35
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• 2019

Objectives : Osteoarthritis is characterized by degeneration of articular cartilage, which is characterized by chronic pain, stiffness and decrease range of motion. The present study was designed to compare the therapeutic effect of Dioscoreae Rhizoma water extract (DRW) and Dioscoreae Rhizoma 30% ethanol extract (DRE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : Osteoarthritis was induced by injection of MIA ($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. After adaptation period for seven days, rats were divided by 5 groups (n=10/group): normal group, control group, positive control (indomethacin 5 mg/kg), DRW 200 mg/kg treated group, DRE 200 mg/kg treated group (n=10/group). The hind paw weight distribution was measured with the changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$) in articulation tissue. Also, the cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factoralpha ($TNF{\alpha}$), interleukin-6 (IL-6), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot analysis. Results : The administration of DRW and DRE significantly decreased the hind paw weight distribution. The ROS and $ONOO^-$ levels of cartilaginous tissue were significantly decreased in DRW and DRE compared to control group. The results showed that DRE decreased inflammatory cytokines such as iNOS and $TNF{\alpha}$. Also DRE decreased MMP-1 and increased TIMP-1. Conclusions : Based on the above results, Dioscoreae Rhizoma extract seems to have the therapeutic effect on osteoarthritis via suppression of inflammation.

• Journal of Life Science
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• v.28 no.2
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• pp.207-215
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• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.51-60
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• 2005

Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.8
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• pp.979-984
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• 2006

Although iron is essential for many physiological processes, excess iron can lead to tissue damage by promoting the generation of reactive oxygen species (ROS). There is increasing evidence that ROS might play an important role in the pathogenesis of cardiovascular disease. However, the effects of iron excess on platelet function and the thrombotic response to vascular injury are not well understood. We examined the effects of iron excess-induced oxidative stress and the antioxidants on platelet aggregation. Oxidative stress was accessed by either free iron $(Fe^{+2})$ or hydrogen peroxide $(H_2O_2)$, as well as their combination on washed rabbit platelets (WPs) in vitro. When WPs were stimulated with either $Fe^{+2}$ alone or a subthreshold concentration of collagen, which gave an aggregatory curve with a little effect, and a dose dependent increase in platelet aggregation was observed by increasing concentrations of $Fe^{+2}$ with $H_2O_2$. This aggregation was associated with the iron-catalyzed formation of hydroxyl radicals from $H_2O_2$, and were inhibited by NAD/NADP (proton acceptor), catalase $(H_2O_2\;scavenger)$, tiron (iron chelator), mannitol (hydroxyl radical scavenger), and indomethacin (cyclooxygenase inhibitor), but not by NADH/NADPH (proton donor), superoxide mutase, and aspirin. However, NADH/NADPH, an essential cofactor for the antioxidant capacity by the supply of reducing potentials, showed the effect of an enhanced radical formation, suggesting a role for NADH/NADPH-dependent oxidase. These results suggest that iron $(Fe^{+2})$ can directly interact with washed rabbit platelets and this aggregation be mediated by OH formation as in the Fenton reaction, inhibited by radical scavengers.