• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.385-393
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• 2008

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we evaluated the effects of the methanol extract of Polytrichum commune Hedw (PCM) (Polytrichaceae) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines release in murine macrophage cell line RAW 264.7. PCM potently inhibits the production of NO, $PGE_2$, tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6. Consistent with these results, PCM also concentration-dependently inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-$\alpha$ and IL-6 at the mRNA levels without an appreciable cytotoxic effect on RAW 264.7 macrophag cells. Furthermore, PCM inhibited LPS-induced nuclear factor-kappa B (NF-$\kappa$B) activation as determined by NF-$\kappa$B reporter gene assay, and this inhibition was associated with a decrease in the nuclear translocation of p65 and p50 NF-$\kappa$B. Taken together, these results suggest that PCM may play an anti-inflammatory role in LPS-stimulated RAW 264.7 macrophages through the inhibitory regulation of iNOS, COX-2, TNF-$\alpha$ and IL-6 via NF-$\kappa$B inactivation.

• Applied Microscopy
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• v.44 no.1
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• pp.21-29
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• 2014

Retinal glial responses to hypertensive glaucomatous injury were spatiotemporally surveyed. Retinas as a whole or vertical sections were processed for anti-glial fibrillary acidic protein (GFAP), anti-Iba1, anti-nerve growth factor (NGF), and anti-tumor necrosis factor (TNF)-${\alpha}$ immunohistochemistry for confocal microscopic analyses. The optic nerve head of paired controls was processed for electron microscopy. GFAP positive astrocytes appeared in the nerve fiber layer in the glaucomatous and control retinas, changing from fine protoplasmic to stout fibrous parallel to glaucomatous duration. Iba1 positive microglia appeared in both retinas, and enormous reaction appeared at the latest glaucomatous. M$\ddot{u}$ller reaction detected by GFAP reactivity expanded from the end feet to whole profile following to duration in the glaucomatous. NGF reactivity expended from the end feet to the proximal radial processes of the M$\ddot{u}$ller cells in both retinas according to glaucomatous duration. TNF-${\alpha}$ immunoreactivity in the nerve fiber layer was stronger in both the glaucomatous and controls than in the normal, and exceptionally at the latest glaucomatous was even lower than the normal. The astrocytes in the optic nerve head are interconnected with each other via gap junction. These results demonstrate that astrocyte reaction propagates to the contralateral via physical links, and TNF-${\alpha}$ is correlated with NGF production for neuroprotection in response to hypertensive glaucomatous injury.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.6
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• pp.751-756
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• 2014

The anti-inflammatory effects of the ethanol extract of Undaria pinnatifida root (UPREE) were investigated using the lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 cells by measuring the production of nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, and IL-$1{\beta}$, and cell proliferation. We found that NO levels were reduced by 34% at $100{\mu}g/mL$. Moreover, the production of IL-6 and TNF-${\alpha}$ was suppressed by the UPREE treatment. In particular, the IL-6 production was inhibited by more than 30% at $100{\mu}g/mL$ UPREE. The proliferation of RAW 264.7 cells was measured by MTT assay, and we found no cytotoxicity in those cells treated with UPREE compared to the control. Our results suggest that UPREE shows promise as a therapeutic anti-inflammatory treatment.

• Korean Journal of Medicinal Crop Science
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• v.24 no.6
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• pp.437-443
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• 2016

Background: Previous phytochemical studies of whole Vernonia cinerea L. plants have identified sesquiterpene lactones, sterols, and triterpenes, which possess anticancer, antifeedant, and antimalarial activities. However, there are no reports of other types of bioactive metabolites. Therefore, the present study aimed to identify phenolic compounds with anti-inflammatory activity in the aerial parts of the plant. Methods and Results: Compounds were isolated from the aerial parts of V. cinerea using a silica and C-18 gel columns and semi-preparative HPLC instrument, and the structures of the compounds were determined using one- and two- dimension nuclear magnetic resonance spectroscopy and mass spectroscopy. The chloroform soluble extracts and isolated compounds were evaluated for their anti-inflammatory potential based on their ability to inhibit nitric oxide production and $TNF-{\alpha}$ induced $NF-{\kappa}B$ activity. Conclusions: Phytochemical study of the aerial parts of V. cinerea led to the isolation of six phenolic compounds. Compound 1 was a major metabolite, and to the best of our knowledge, compounds 2 - 6 were isolated from V.cinerea for the first time. Among the isolates, compounds 1 and 3 exhibited $TNF-{\alpha}$-induced $NF-{\kappa}B$ activity with $IC_{50}$ values of 7.5 and 11.5 M, respectively, and the inhibitory activity of phenyl propanoid compound 3 on $TNF-{\alpha}$-induced $NF-{\kappa}B$ was evaluated for the first time.

• The Journal of Korean Medicine
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• v.21 no.2
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• pp.52-59
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• 2000

Objectives: The root and stem of Sinomenium acutum has been used for treatment of arthritis and neuralgia in oriental medicine. To find new substances of the anti-anaphylactic drugs, we studied Sinomenium acutum. Methods: To investigate the effect of this plant, the effect on anaphylactic reaction, plasma histamine level, and tumor necrosis $factor-{\alpha}-(TNF-{\alpha})$ production were measured after the aqueous extract of Sinomenium acutum stem (SSAE) was administrated to mice and rats. Results: The SSAE (0.1 to 1000 mg/kg) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, SSAE reduced compound 48/80-induced anaphylactic reaction with 50% at the dose of 1000 mg/kg. SSAE (100 to 1000 mg/kg) also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with SSAE at a concentration ranging from 0.1 to 1000 mg/kg, the plasma histamine levels were reduced in a dose-dependent manner. SSAE (1 to 1000 g/ml) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMCs) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMCs, when SSAE was added, increased compared with that of a normal control. In addition, SSAE (0.1 g/ml) had a significant inhibitory effect on anti-DNP IgE-induced $TNF-{\alpha}$ production. Conclusions: These results indicate that SSAE inhibits mast cell-mediated anaphylactic reactions and $TNF-{\alpha}$ production from mast cells.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.141-146
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• 2018

Periodontitis is generally a chronic disorder characterized by breakdown of tooth-supporting tissues, producing dentition loss. Porphyromonas gingivalis (P. gingivalis), a Gramnegative anaerobic rod, is one of the major pathogens associated with periodontitis. Neutrophils are first line defense cells in the oral cavity that play a significant role in inflammatory response. Xylitol is a known anti-caries agent and has anti-inflammatory effects. In this study, we conducted experiments to evaluate anti-inflammatory effects of xylitol on P. gingivalis infected neutrophils for possible usage in prevention and treatment of periodontal infections. P. gingivalis was intraperitoneally injected and peritoneal lavage was collected for cytokine determination. For in vitro study, neutrophils were collected from mouse peritoneal cells after zymosan injection or bone marrow cells. Neutrophils were stimulated with live P. gingivalis and ELISA was used to determine the effect of xylitol on P. gingivalis induced cytokine production. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ concentration and neutrophil population in the peritoneal lavage was increased in P. gingivalis-infected mouse. Peritoneal cells infected with live P. gingivalis revealed significantly increased production of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ at multiplicity of infection of 10. Neutrophils from bone marrow and peritoneal lavage revealed increased production of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. Xylitol significantly mitigated P. gingivalis induced cytokine production in neutrophils. Findings indicate that xylitol is an anti-inflammatory agent in neutrophils infected with live P. gingivalis, that suggests its use in periodontitis management.

• The Korean Journal of Food And Nutrition
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• v.34 no.2
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• pp.146-155
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• 2021

This study observed the anti-inflammatory effect of the polysaccharide derived from the mycelium of Tremella fuciformis in mice with colitis induced with dextran sulfate sodium (DSS). The experimental groups were normal, DSS, DSS-TFL50, DSS-TFH100, and suflasalazine. Body weights, colon lengths, and organ weights were measured, and the plasma level of pro-inflammatory cytokine and mRNA and protein expression in colon tissue were analyzed. Body weight loss, a symptom of DSS-induced colitis, was suppressed by DSS-TF and the speed of weight recovery proceeded rapidly. In addition, DSS-TF showed a significant inhibitory effect on the decrease of colon length typically caused by colon damage. TNF-α, IL-6 and IL-1β cytokine levels in plasma were reduced in DSS-TF and positive control groups. TNF-α, COX-2 and IL-1β mRNA expression in colon tissue were inhibited in DSS-TF and positive control, and it was significantly different from that of the DSS group. The protein expression of inflammation-related genes (IL-6, TNF-α and COX-2) in the colon tissue was significantly increased by DSS compared to that of the normal group, but by DSS-TFL50, DSS-TFH100 and sulfasalarin decreased. In conclusion, the polysaccharide derived from the mycelium of Tremella fuciformis showed the anti-inflammatory effect on DSS-induced colitis in mice.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.4
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• pp.1-11
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• 2021

Objectives Hwanggeumjakyak-tang (HJT) has traditionally been used to treat gastrointestinal inflammatory diseases; however, its protective effects against neuronal inflammation are still undiscovered. Methods We investigated the anti-neuroinflammatory effects of HJT water extract on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells. BV2 cells were treated with LPS (1 ㎍/mL) 1 hour prior to the addition of HJT. We measured cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and nitrite production using the Griess assay. We performed a reverse transcription-polymerase chain reaction assay to measure messenger RNA expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Western blot analysis was performed to determine protein expression of mitogen-activated protein kinases (MAPKs) and inhibitor of nuclear factor kappa B (NF-κB)α. Results HJT inhibited excessive nitrite release in LPS-stimulated BV2 cells and also significantly inhibited inflammatory cytokines such as IL-1β, IL-6, and TNF-α in LPS-stimulated BV2 cells. Moreover, HJT significantly suppressed LPS-induced MAPK and NF-κB activation and inhibited the elevation of IL-1β, IL-6, and TNF-α in the brain of LPS-injected mice. Conclusions Our study highlights the anti-neuroinflammatory effects of HJT via MAPK and NF-κB deactivation.

• The Journal of Korean Medicine
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• v.43 no.4
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• pp.20-32
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• 2022

Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG's anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and Iκ-Bα by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of Iκ-Bα but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1β, IL-6, and TNF-α via the deactivation of JNK, p38 and nuclear factor (NF)-κB on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.4
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• pp.1-14
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• 2023

Objectives The anti-inflammatory and anti-arthritic effects of Youngseonjeatonguem (靈仙除痛飮, YSJTU) was evaluated in a cellular model using RAW264.7 macrophages, which are involved in osteoarthritis (OA), and an animal model using Sprague-Dawley (SD) rats, and a possible mechanism of anti-arthritic actions of YSJTU was presented. Methods RAW264.7 macrophages were activated by lipopolysaccharide (LPS). The production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-𝛼, interleukin [IL]-1𝛽, and IL-6) and inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) was determined by ELISA and Griess assay, respectively. Western blot was performed to determine inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. OA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joint of SD rats. Results In RAW264.7 macrophages, YSJTU reduced LPS-induced production of TNF-𝛼, IL-1𝛽, and IL-6. In addition, YSJTU inhibited LPS-induced production of NO and PGE2 by suppressing iNOS and COX-2 expression. In SD rats, YSJTU improved MIA-induced OA by reducing swelling, skin heat, and cartilage degradation. In addition, YSJTU reduced serum levels of TNF-𝛼, IL-1𝛽, and IL-6, along with its significant decrease in serum levels of NO and PGE2. Conclusions These results suggest that YSJTU may exert anti-arthritic effect, at least in part, by inhibiting macrophage-mediated joint inflammation.