• Nutrition Research and Practice
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• v.14 no.3
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• pp.175-187
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• 2020

BACKGROUND/OBJECTIVES: In this study, we investigated the beneficial effects of skate cartilage extracts containing chondroitin sulfate (SCS) on hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet (HCD)-fed mice in comparison with the effects of shark cartilage-derived chondroitin sulfate (CS). MATERIALS/METHODS: Low-density lipoprotein receptor knockout (LDLR-KO) mice were fed HCD with an oral administration of CS (50 and 100 mg/kg BW/day), SCS (100 and 200 mg/kg BW/day), or water, respectively, for ten weeks. RESULTS: The administration of CS or SCS reduced the levels of serum triglyceride (TG), total cholesterol (TC), and LDL cholesterol and elevated the levels of high-density lipoprotein cholesterol, compared with those of the control group (P < 0.05). Furthermore, CS or SCS significantly attenuated inflammation by reducing the serum levels of interleukin (IL)-1β and hepatic protein expression levels of nuclear factor kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and IL-1beta (P < 0.05). In particular, the serum level of tumor necrosis factor-alpha was reduced only in the 100 mg/kg BW/day of SCS-fed group, whereas the IL-6 level was reduced in the 100 and 200 mg/kg BW/day of SCS-fed groups (P < 0.05). In addition, lipid peroxidation and nitric oxide production were attenuated in the livers of the CS and SCS groups mediated by the upregulation of hepatic proteins of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase (P < 0.05). CONCLUSIONS: These results suggest that the biological effects of SCS, similar to those of CS, are attributed to improved lipid profiles as well as suppressed inflammation and oxidative stress induced by the intake of HCD.

• Journal of Microbiology and Biotechnology
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• v.27 no.8
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• pp.1529-1538
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• 2017

Klebsiella pneumoniae is an opportunistic and clinically significant emerging pathogen. We investigated the relative roles of Toll-like receptor (TLR) 2 and TLR4 in initiating host defenses against K. pneumoniae. TLR2 knockout (KO), TLR4 KO, TLR2/4 double KO (DKO), and wild-type (WT) mice were inoculated with K. pneumoniae. Mice in each group were sacrificed after either 12 or 24h, and the lungs, liver, and blood were harvested to enumerate bacterial colony-forming units (CFU). Cytokine and chemokine levels were analyzed using enzyme-linked immunosorbent assay and real-time PCR, and pneumonia severity was determined by histopathological analysis. Survival was significantly shortened in TLR4 KO and TLR2/4 DKO mice compared with that of WT mice after infection with $5{\times}10^3CFU$. TLR2 KO mice were more susceptible to infection than WT mice after exposure to a higher infectious dose. Bacterial burdens in the lungs and liver were significantly higher in TLR2/4 DKO mice than in WT mice. Serum $TNF-{\alpha}$, MCP-1, MIP-2, and nitric oxide levels were significantly decreased in TLR2/4 DKO mice relative to those in WT mice, and TLR2/4 DKO mice showed significantly decreased levels of $TNF-{\alpha}$, IL-6, MCP-1, and inducible nitric oxide synthase mRNA in the lung compared with those in WT mice. Collectively, these data indicate that TLR2/4 DKO mice were more susceptible to K. pneumoniae infection than single TLR2 KO and TLR4 KO mice. These results suggest that TLR2 and TLR4 play cooperative roles in lung innate immune responses and bacterial dissemination, resulting in systemic inflammation during K. pneumoniae infection.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.9
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• pp.1226-1234
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• 2012

3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.1
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• pp.18-25
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• 2017

This study describes the preliminary evaluation of antioxidant and anti-inflammatory activities of Allium hookeri. A. hookeri was extracted using crude extract and then fractionated sequentially with n-hexane, $CH_2Cl_2$, EtOAc, and n-BuOH. To screen for antioxidant and anti-inflammatory agents effectively, we first examined the inhibitory effect of A. hookeri extracts on production of oxidant stresses (2,2-diphenyl-1-picrylhydrazyl, xanthine oxidase, and superoxide). In addition, we examined the inhibitory effects of A. hookeri on production of pro-inflammatory factors (nitric oxide, prostaglandin $E_2$, inducible nitric oxide synthase, and cyclooxygenase-2) in murine macrophage RAW 264.7 cells stimulated with lipopolysaccharide. Of the sequential solvent fractions of A. hookeri, EtOAc fractions showed decreased production of oxidant stresses, and $CH_2Cl_2$ and EtOAc fractions of A. hookeri inhibited production of pro-inflammatory factors. EtOAc fraction inhibited production of pro-inflammatory cytokines (interleukin-6 and -$1{\beta}$). These results suggest that A. hookeri has significant effects on oxidant stresses and pro-inflammatory factors and is a possible antioxidant and anti-inflammatory therapeutic and preventive material.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.1
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• pp.20-26
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• 2016

This study investigated the fermentation effect of Taraxacum platycarpum Dahlst. leaf extracts using Hericium ernaceum mycelia to test antioxidant and anti-inflammatory activities in vitro. The antioxidant activities of fermented or non-fermented extracts of T. platycarpum leaves were determined by 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, ferric reducing antioxidant power, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity. The leaf extract of T. platycarpum showed higher antioxidant activity than extract of fermented leaves. However, ethanolic extract of fermented T. platycarpum leaves decreased levels of nitric oxide production and pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-${\alpha}$ in lipopolysaccharide-stimulated RAW 264.7 cells. Moreover, fermented leaf extract suppressed protein expression of inducible nitric oxide synthase in RAW 264.7 cell culture. Therefore, the enhanced anti-inflammatory activity of ethanolic extracts of fermented T. platycarpum leaves might be attributed to the molecular conversion of leaf ingredients during fermentation and the active ingredients might have specific affinity with ethanol during extraction.

• The Journal of Korean Medicine
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• v.27 no.1 s.65
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• pp.184-195
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• 2006

Objectives : Betula Platyphylla(BP) is a traditional analgesic, anti-fungal, anti-inflammatory herb used in Chinese 1medicine. However, no information is available to explain its action. In this study. we investigated the anti-inflammatory 1effects of BP to elutidate the molecular pharmacological activity in the ethanol extract of BP(BPE). Methods : We performed WTS assay in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages with BPE. Nitrite was measured by Griess assay, prostaglandin E2 (PGE2) by enzyme-linked immunosorbent assay (ELISA) in LPS induced RAW264.7 macrophages with BPE. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) were determined by Western blot. Activation of nuclear factor-kappaB (NF-kB) was measured by electrophoretic mobility shift assay (EMSA). Results : BPE significantly suppressed production of nitric oxide (NO) and PGE2 in LPS-induced RAW264.7 macrophages in a dose-dependent manner. The maximal inhibition rate of NO and PGE2 production by BPE was ca. 88.8% and 93% at the concentration of $100{\mu}g/ml$ (non-cytotoxic concentration), respectively. BPE also decreased iNOS protein and COX-2 protein in LPS-induced RAW264.7 macrophages. EMSA demonstrated that BPE inhibited the DNA binding activity of the NF-kB. Conclusions : These results suggest that BPE inhibits NF-${\kappa}B$-mediated gene expression and downregulates inflammatory mediator production in RAW264.7 macrophages.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.167-175
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• 2001

Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. Hige- namine, a positive inotropic isoquinoline alkaloid, has been used traditionally as cardiac stimulant, and reported to reduce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression in LPS- and/or cytokine-activated cells in vitro and in vivo. Therefore, we investigated whether higenamine modulates the production of proinflammatory cytokines in myocardial infarction. In addition, effects of higenamine on antioxidant action and antioxidant enzyme expression (MnSOD) were studied. Myocardial infarction (MI) was confirmed by measuring left ventricular (LV) pressure after occlusion of the left anterior descending coronary artery (LAD) for 5 weeks in rats. Treatment of higenamine (10 mg/kg/day) reduced infarct size about 35 %, which accompanied by reduction of production TNF-$\alpha$, IL-6, but not IFN-${\gamma}$ and IL-1$\beta$ in the myocardium. The expression of TNF-$\alpha$ mRNA in infracted myocardium was significantly reduced by higenamine. Although iNOS mRNA was not detected, nitrotyrosine staining was significantly increased in myocardium of Ml compared to higenamine-treated one, Indicating that peroxynitrite-induced damage is evident in MI. Cytochrome c oxidation by peroxynitrite was concentration-dependently reduced by higenamine, an effect which was almost compatible to glutathion. Higenamine treatment did not affect the expression of MnSOD mRNA in myocardial tissues in MI. Taken together, higenamine may be beneficial in oxidative stress conditions such as ischemic-reperfusion injury and MI due to antioxidant action as well as modulation of cytokines.

• Journal of Life Science
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• v.28 no.4
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• pp.429-434
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• 2018

In this study, we investigated the potential of Glechoma hederacea var. longituba 70% ethanol extract as a natural functional material by examining the anti-inflammatory effect of it. Macrophages results in (Raw 264.7) induced by lipopolysaccharide (LPS). Confirming the viability of the macrophages Glechoma hederacea var. longituba 70% ethanol extract showed a 95.8% survival rate at $1,000{\mu}g/ml$ concentration. Anti-inflammatory activity was examined the inhibitory tests on the production of LPS included nitric oxide (NO) in RAW 264.7 cells by Griess assay. The result showed that NO production deterrent effect of 37.4% at a concentration of $1,000{\mu}g/ml$. The deterrent effect of GG 70% ethanol extract on protein expression of inducible NOS (iNOS) and Cyclooxygenase-2 (COX-2) was measured by Western blotting using the concentrations 50, 100 and $500{\mu}g/ml$, with ${\beta}$-actin used as the positive control. The inhibitory effect of iNOS and COX-2 mRNA expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) using 50, 100 and $500{\mu}g/ml$ concentration of GG 70% ethanol extract, with GAPDH used as the positive control. In experiments using Western blot and RT-PCR when compared with the control group vitamin C it was confirmed that the 70% ethanol extract from GG suppressed. When compiling the results of this study, we confirmed the possibility of GG 70% ethanol extract as an anti-inflammatory material.

• Korean Journal of Acupuncture
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• v.30 no.4
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• pp.264-271
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• 2013

Objectives : To observe the changes in the expression of neurotransmitters NO and enzymes that create NO, such as nNOS, iNOS and eNOS, upon the needle insertion on river point, one of the five transport points of three yang meridians on the forefoot. Methods : Based on rats, needle was inserted on both sides of LI5, SI5 and TE6, which are river points of three yang meridians on the forefoot, and were retained for five minutes. After the retention, blood was drawn via cardiac puncture and tissues from each point around meridian vessels were extracted to be examined on the changes of the expression of NO, as well as of nNOS, iNOS and eNOS. Results : In terms of the effect on NO creation in tissues, none of the experimental groups showed any significant change compared to the Normal group. In terms of the effect on expression of nNOS within tissues, LI5 and SI5 showed significant increase based on the results of immunohistochemistry. In iNOS within tissues, LI5 and SI5 showed significant increase based on the results of immunohistochemistry. In eNOS within tissues, SI5 showed significant increase based on the results of immunohistochemistry. Conclusions : The effect on the function of NO, nNOS, iNOS and eNOS of needle insertion on the river points of three yang meridians on the forefoot could be observed, and based on this study, it is considered that the effect of needle stimulation on the changes of nervous system could be found out through additional research.

• Journal of Life Science
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• v.22 no.5
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• pp.657-664
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• 2012

The aim of this study is to screen a therapeutic agent with a cognitive function. The inhibitory effect of $Curcuma$ $longa$ hot water extract (CLWE) on the angiotension-converting enzyme and acetylcholinesterase derived from rabbit lungs and neural cells (PC12), as well as its antioxidant effect, was investigated in this study. Thus, for the first time, the direct scavenging effect of CLWE on DPPH radicals, superoxide anions, hydroxyl radicals, lipid peroxidation, reducing power, and the protective effect of DNA oxidation related to oxidative stress was evaluated in vitro. In addition, it was observed that CLWE especially exhibited a scavenging effect on reducing power and superoxide anions in this study. CLWE showed a protective effect on DNA oxidation produced by hydroxyl radicals. Furthermore, CLWE inhibited the activity of angiotensin-converting enzymes above 0.25%. Additionally, the extract inhibited oxidative stress and inducible nitric oxide in neuronal cells. Therefore, these results demonstrated that CLWE has antioxidant activity and neuronal cell protective effects, suggesting that it may have great potential as a natural source for human health.