• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.183-189
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• 2015

Foeniculum vulgare Mill. (fennel) is used to flavor food, in cosmetics, as an antioxidant, and to treat microbial, diabetic and common inflammation. No study to date, however, has assessed the anti-inflammatory effects of fennel in experimental models of inflammation. The aims of this study were to investigate the anti-inflammatory effects of fennel in model of lipopolysaccharide (LPS)-induced acute lung injury. Mice were randomly assigned to seven groups (n=7~10). In five groups, the mice were intraperitoneally injected with 1% Tween 80-saline (vehicle), fennel (125, 250, $500{\mu}l/kg$), or dexamethasone (1 mg/kg), followed 1 h later by intratracheal instillation of LPS (1.5 mg/kg). In two groups, the mice were intraperitoneally injected with vehicle or fennel ($250{\mu}l/kg$), followed 1 h later by intratracheal instillation of sterile saline. Mice were sacrificed 4 h later, and bronchoalveolar lavage fluid (BALF) and lung tissues were obtained. Fennel significantly and dose-dependently reduced LDH activity and immune cell numbers in LPS treated mice. In addition fennel effectively suppressed the LPS-induced increases in the production of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, with $500{\mu}l/kg$ fennel showing maximal reduction. Fennel also significantly and dose-dependently reduced the activity of the proinflammatory mediator matrix metalloproteinase 9 and the immune modulator nitric oxide (NO). Assessments of the involvement of the MAPK signaling pathway showed that fennel significantly decreased the LPS-induced phosphorylation of ERK. Fennel effectively blocked the inflammatory processes induced by LPS, by regulating pro-inflammatory cytokine production, transcription factors, and NO.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.152-162
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• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.379-389
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• 2005

Objectives: It is well known that aging and aging-related diseases are linked to the increased level of oxidative stress caused by reactive oxygen species(ROS) and reactive nitrogen species(RNS). Nonprotein-SH decreases during aging, while substances such as ROS, nitric oxide(NO), peroxynitrite($ONOO^-$), myeloperoxidase(MPO), and dityrosine show a significant increase. This study investigated the effect of Ichungwhan on the aging process by examining its effect on the generation of the above-mentioned substances. Methods: Four comparison groups of SD rats were used. They were 6 month-old rats, 24 month-old rats, and 24 month-old rats fed with food containing 0.1% and 0.3% of Ichungwhan extract. The amount of NO, $ONOO^-$, and ROS in the rats' kidneys were examined using a fluorescence microplate reader. The reagents used for this purpose include: dihydrorhodamine 123 (DHR 123), 2',7' -dichlorodihydrofluorescein, diacetate(DCFDA), and 4,5-diaminofluorescein(DAF-2). A spectrophotometer was used to investigate the reactivity of nonprotein-SH and myeioperoxidase(MPO), using reagents such as trichloroacetic acid(TCA) and tetramethylbenzidine(TMB). The amounts of MPO protein and dityrosine were measued by western blot. Results: The observed effects of Ichungwhan on rats were as follows: increase of nonprotein-SH; effective decrease of RNS level by suppression of the generation system of $ONOO^-$ and NO; decrease of ROS level; decrease of the MPO reactivity and the subsequent reduction of amount of MPO protein; retardation of dityrosine formation. It can be hypothesized, therefore, that Ichungwhan affects both the earlier and later phases of the molecular inflammatory process, and retards the aging process. Conclusions: Empirical evidence in this study supports a role for Ichungwhan in generation mechanisms of aging process-linked substances ROS, NO, $ONOO^-$, nonprotein-SH, MPO and dityrosine. Affects contrary to the aging process observed in rats beg further empiricism to investigate potential application of Ichungwhan as a medication for age-related diseases in humans.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.43 no.1
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• pp.39-45
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• 2010

Chlorella has been reported to have certain beneficial physiological effects, including hypocholesterolemic, antihypertensive, antioxidative, and anti-tumor activities in animal and human studies. The aim of this study was to determine the anti-inflammatory activities of an 80% methanol extract(CE-Met), hexane fraction (CE-Hex), and ethyl acetate fraction (CE-EA) of Chlorella ellipsoidea in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage. Treatment with various concentrations of the C. ellipsoidea extract resulted m a significant, dose-dependent reduction in nitric oxide (NO) production by LPS-induced macrophages. The C. ellipsoidea extract significantly inhibited LPS-induced NO production accompanied by an attenuation of IL-6 and TNF-$\alpha$ formation in macrophages. These results suggest potent inhibit이y effects on the production of inflammatory mediators by a C. ellipsoidea extract. Thus, C. ellipsoidea extract may be a potent anti-inflammatory agent for troubled skin.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.296-301
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• 2015

Chronic kidney diseases are based on uncontrolled immunological and inflammatory responses to pathophysiological renal circumstances such as glomerulonephritis, which is caused by immunological mechanisms of glomerular inflammation with increased production of renal pro-inflammatory cytokines. Pentoxifylline (PTX) exhibits anti-inflammatory properties by inhibiting cytokine and chemokine production through aggregation of erythrocytes and thrombocytes. We synthesized a series of 1,7-substituted methylxanthine derivatives by the Traube purine reaction, and the formation of purine ring was completed through nitrosation, a reduction of the nitroso to the amine by catalytic hydrogenation as derivatives of PTX. Then we studied biological activities such as renal anti-inflammatory effects of the synthesized compounds in the production of cytokines such as nitric oxide (NO), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) and of chemokines such as monocyte chemoattractant protein-1 and IL-8 in Raw 264.7 and HK-2 cells. Renal antiinflammatory activities of this novel series of N-1 and N-7-substituted methylxanthine showed that the N-7 methyl-group-substituted analogs (S7b) showed selective 61% and 77% inhibition of the production of NO and IL-8. The other replacement of the N-1-(CH₂)₄COCH₃ roup, as in the case of compound S6c, also showed an effective 50% and 77% inhibition of TNF-α and IL-8 production in LPS-stimulated Raw 264.7 and HK-2 cells.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.317-322
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• 2004

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is limited by their ability to induce gastrointestinal injury. It has been shown that nitric oxide (NO), similar to pro staglandins (PGs), appears to play an important role in gastric mucosal defence. We hypothesized that NSAIDs contained NO group would be less acutely toxic to the gastric mucosa, but would not interfere with their ability to suppress inflammatory process in rats. We have compared the ulcerogenic and anti-inflammatory effect of CW-501029 (NO-NSAIDs), CW-501027 (NSAIDs) and indomethacin. Both did not change mean blood pressure and heart rates, indicating that they had no side effect on cardiovascular system. We found that CW-501029 increased nitrite/nitrate levels without changing of blood pressure and heart rates. We suggest that it may help gastric mucosal blood flow, the which helps reducing the discomfort in astrointestinal system. Carrageenan-induced PGE2 increase was reduced in a similar tendency when compared CW-501027 or CW-501027 with control in back exudate of rats, but CW-501029 less reduced PGE2 than CW-502027 or indomethacin in gastric tissues. CW-501027 or CW-501029 reduced platelet aggregation. From these results we suggest that CW-501029 may improve the side effect by reduction of short-term gastric injury and less inhibition of PGs synthesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2845-2850
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• 2013

Background: Breast cancer is one of the most frequent diseases in women today. Little information exists on modifiable lifestyle factors including effects of ginger supplements (as an anti-oxidant and anti-inflammatory herbal) and water-based exercise on biomarkers related to oxidative stress such as malondialdehyde (MDA), nitric oxide (NO) and glutathione peroxidase (GPx) and adiponectin in obese women with breast cancer. The aim of this study was to determine the single and concomitant effect of 6-wks water-based exercise and oral ginger supplement on the aforesaid markers in obese women with breast cancer. Materials and Methods: Forty women diagnosed with breast cancer ($48{\pm}5.4$ years, $76{\pm}9$ kg, fat mass $41.8{\pm}4%$), volunteered to participate in the study. Subjects were randomly assigned into four groups; placebo, water-based exercise, ginger supplement and water-based exercise+ginger supplement groups. Subjects in the ginger supplement group and the water-based exercise+ginger supplement group orally received 4 capsules (each capsule contained 750 mg), 7 days a week for 6 weeks. The water-based exercise program featured progressive increase in intensity and time, ranging from 50% to 75% of heart rate reserve, in a pool with 15 meters width, 4 times a week for 6 weeks. Fasting blood samples were collected at pre-test and post-test time points. Results: The ginger supplementation and or the water-base exercise resulted in an increase of adiponectin, NO and GPx and reduction MDA, as compared to pre-test values. However, the combined intervention (water-base exercise and ginger supplement) group showed significantly a far better effect on the biomarkers related to oxidative stress and adiponectin levels, as compared to the waterbase exercise or ginger supplement alone groups and the age-matched placebo group. Conclusions: Our results revealed that water-base exercise is a non-drug therapeutic strategy to reduce systemic stress in obese women suffering from breast cancer. Further, ginger supplementation alone or in combination with training, also play an important role in the pathogenesis of oxidative stress in obese women diagnosed with breast cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1583-1587
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• 2015

Bile acids are endogenous metabolites that aid in the digestion and absorption of ingested fat and fat-soluble vitamins. However, high concentrations of deoxycholic acid (DCA) in the colon are associated with high incidence of colorectal cancer. In the present study, the binding of persimmon extracts to DCA in order to decrease inflammatory stress induced by DCA in a small intestinal epithelial cell line, Caco-2, was investigated. Young and ripened persimmons were extracted with distilled water (DW), ethanol, and acidic ethanol. Further, DW extract residue was re-extracted with acidic ethanol. Of the obtained extracts, acidic ethanol extract of young persimmon showed the highest bile-acid binding capacity. Moreover, acidic ethanol extract of young persimmon significantly inhibited nitric oxide production in Caco-2 cells stimulated with DCA and prevented significant reduction of trans-epithelial electric resistance. Based on these results, acidic ethanol extract of young persimmon can be used as a functional ingredient to enhance gastrointestinal health.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.113-122
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• 2003

Objective : The aim of this study was to evaluate the efficacy of Gagamchunggan-tang on anti-inflammation reaction with lipopolysaccharide (LPS)-induced HepG2 cell. Method : We examined the effects of the Gagamchunggan-tang, a traditional drug for liver inflammation, on the process of lipopolysaccharide(LPS)-induced nuclear factor-${\kappa}Bp65(NF-{\kappa}Bp65)$ activation in HepG2 cell. SDS-PAGE, Western blotting, Immunofluorescence staining were studied. Results : Immunoblot analysis showed that the level of nucleic $NF-{\kappa}Bp65$ was rapidly up-regulated and cytosolic inhibitory $I-{\kappa}B{\alpha}$ was down-regulated by LPS challenge. While Gagamchunggan-tang inhibited an increase of $NF-{\kappa}Bp65$ and degradation of $I-{\kappa}B{\alpha}$ in HepG2 cell. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-${\alpha}(TNF-{\alpha})$, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2), are repressed by Gagamchunggan-tang. It may be concluded that Gagamchunggan-tang attenuates the progress of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation. Conclusion : The Gagamchunggan-tang would be useful as a therapeutic agent for endotoxin-induced liver disease.

• Natural Product Sciences
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• v.22 no.3
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• pp.193-200
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• 2016

This study describes the anti-inflammatory, anti-oxidant, and melanogenesis inhibition activities of methanol extract and various organic solvent fractions of Arecae Pericarpium. We examined the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells, 1,1-diphenyl-2-picrylhydrazine (DPPH) scavenging activity, mushroom tyrosinase inhibition activity and melanin contents. The study showed that, among all tested fractions, methylene chloride fraction showed the strongest inhibition of LPS-induced NO production in RAW 264.7 cells ($IC_{50}$ value $8.89{\mu}g/mL$) and DPPH radical scavenging activity ($EC_{50}$ value $21.39{\mu}g/mL$). Methylene chloride and ethyl acetate fractions similarly inhibited mushroom tyrosinase activity. Methanol extract exhibited strongest reduction of melanin content in B16F10 melanoma cells. Based on the bioactivity assay results, methylene chloride and ethyl acetate fractions were further separated. Eight phenolic compounds were isolated, which are dimeric syringol (1), catechol (2), 4-hydroxybenzaldehyde (3), vanillin (4), 4-hydroxyacetophenone (5), apocynin (6), protocatechuic acid (7) and 4-hydroxybenzoic acid (8). Among the isolated compounds tested, catechol showed the strongest inhibition of LPS-induced NO production in RAW 264.7 cells. Catechol also showed the concentration-dependent NF-${\kappa}B$ inhibition activity. Arecae Pericarpium might have potentials to be developed as anti-inflammatory agent or dermatological product for skin-whitening agent.