• The Korea Journal of Herbology
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• v.22 no.4
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• pp.65-73
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• 2007

Objective : Salvia miltiorrhiza Bunge (Labiatae) (SM), an eminent herbal plant, has been widely used in traditional Chinese medicine for the treatment of vascular diseases such as hypertension. The aim of this study was to determine whether SM inhibits production of nitrite, an index of NO, and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. And this study investigated whether or not SM could reduce tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced inflammatory response in human vascular aortic smooth muscle cells (HASMC) and umbilical vein endothelial cells (HUVEC). Methods : Cytotoxic activity of SM on RAW 264.7 cells was using 5-(3-caroboxymeth-oxy phenyJ)-2H-tetra-zolium inner salt (MTS) assay. We measured the NO production using Griess Reagent System. Production of Proliflammatory cytokines was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Results : Our results indicated that SM significantly inhibited the LPS-induced NO production accompanied by an attenuation of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), IL-6 and monocyte chemoattractant protein (MCP)-1 formation in macrophages. SM decreased TNF-${\alpha}$-induced IL-8, IL-6 production, and intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression. Conclusion : These results indicate that SM has potential as an anti-inflammatory agent.

• Advances in Traditional Medicine
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• v.10 no.1
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• pp.7-12
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• 2010

Typha orientalis' stem (TOS) is traditionally used as an herbal medicine for difficulty in urination, galactophoritis purulenta, whooping cough, and allergic dermatitis. However, its effect in experimental models remains unknown. Here, we report the effect of TOS on the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine production and extracellular signal-regulated kinase (ERK) activation in the human mast cell line, HMC-1. TOS inhibited PMA plus A23187-induced cytokines such as tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin (IL)-6. Maximal inhibition rate of TNF-$\alpha$ and IL-6 production by TOS (1 mg/ml) was about 44.02%, and 45.20%, respectively (P < 0.05). In addition, TOS inhibited the expression of TNF-$\alpha$ and IL-6 mRNA under the same condition. Moreover, TOS partially blocked PMA plus A23187-induced ERK phosphorylation. These results suggested TOS could inhibit the cytokine production through blocking of ERK activity.

• Korean Journal of Clinical Pharmacy
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• v.25 no.4
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• pp.246-253
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• 2015

Background & Object: Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes ankylosis and deformation of axial joints. Since current medicine cannot cure the disease yet, alleviating pain and preventing deformation with medications are the main therapy for patients with AS. The key medications for these purposes include nonsteroidal anti-inflammatory drugs (NSAIDs), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) inhibitors. This study aims to analyze prescribing patterns of AS patients in South Korea. Method: National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 was analyzed. Patients with AS were identified with Korean Standard Classification of Diseases code-6, which was M45. The rates of prescription, discontinuation, and switching ingredients were calculated for each medication during 2013. Results: Total number of patients was 655, and most of them were male (n = 514, 78.5%). Of all age groups, the proportion of 30-40 year old patients was the greatest (35.1%). The most utilized drug class was NSAIDs (82.4%). Less than half of patients were prescribed $TNF-{\alpha}$ inhibitors (n = 212, 32.4%). Meloxicam, aceclofenac, and celecoxib were the most frequently prescribed NSAIDs. In case of $TNF-{\alpha}$ inhibitors, adalimumab, etanercept and infliximab were the top three most prescribed drugs. Although not recommended by the current practice guideline, significant proportions of patients were identified using disease modifying anti-rheumatic drugs (DMARDs). Conclusion: Considering the current practice guideline and previous studies about the efficacy, the use of DMARDs should be reduced and medical insurance term in South Korea should be re-examined.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.135-143
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• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.383-388
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• 1998

The present study was aimed to investigate the preventive effects of rebamipide on the multiple organ dysfunction in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS) in comparison with that of methotrexate. Endotoxemia for 6 hours resulted in little change in the levels of hemoglobin and neutrophils. However, treatment with methotrexate decreased significantly the numbers of circulating neutrophils. Significant increases in serum alanine aminotransferase (ALT,958 $\pm$ 250 lU/L, p<0.001) and aspartate aminotransferase (AST, 1350 $\pm$ 295 lU/L, p<0.001) levels induced by endotoxemia were significantly decreased by rebamipide and methotrexate. The increased level of lactic acid dehydrogenase (LDH) by LPS (2850 $\pm$ 467 lU/L, p<0.05) was significantly inhibited by rebamipide, but not by methot.elate. The elevated serum creatinine (1.2$\pm$0.1, p.0.05) and urea levels (55.3$\pm$6.5 mg/dL, p.0.01) by LPS were also decreased by rebamipide, but not by methotrexate. In line with these results, the plasma concentration of tumor necrosis factor-$\alpha$ (TNF-7,167 $\pm$ 20 pg/mL) was significantly increased upon injection of endotoxin at 1 hour by 1570$\pm$100 pg/mL, and declined to 312$\pm$35 pg/mL at 6 hours. The TNF-$\alpha$ level at 6 hours was significantly decreased by rebamipide to 207$\pm$8 pg/mL (P<0.05). Taken together, it is summarized that rebamipide inhibits the development of multiple ogran dysfunction by inhibition of neutrophil activation in association with inhibition of TNF-$\alpha$ formation in a murine model of endotoxemia.

• Journal of Periodontal and Implant Science
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• v.42 no.1
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• pp.3-12
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• 2012

Purpose: Anti-rheumatic agents target common molecular pathways of inflammation in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to determine the relative effect of anti-rheumatic agents on the levels of inflammatory biomarkers and periodontal inflammation in RA patients with periodontitis. Methods: A systematic review and meta-analysis were conducted of studies comparing periodontal parameters of inflammation, such as bleeding on probing, and biomarkers of inflammation in RA patients with periodontitis and healthy adults with and without periodontitis. The search included the electronic databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar, inclusive through October 2011, with no language restrictions. Hand searches were conducted of the bibliographies of related journals and systematic reviews. Observational and interventional studies assessing the effects of antirheumatic therapy qualified for inclusion. Two reviewers performed independent data extraction and risk-of-bias assessment. Of the 187 identified publications, 13 studies fulfilled the inclusion criteria. Results: When compared to healthy adults without periodontitis, RA subjects were found to have significantly higher levels of bleeding on probing and limited evidence of higher levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in gingival crevicular fluid and saliva. No consistent differences were found in periodontal parameters and inflammatory biomarkers between RA subjects and adults with periodontitis. Studies evaluating the effect of anti-TNF-${\alpha}$ therapy in RA subjects with periodontitis have yielded inconsistent results. Conclusions: There are limited data, however, to suggest that anti-TNF-${\alpha}$ agents can reduce local production of inflammatory cytokines and periodontal inflammation in RA patients with periodontitis.

• Preventive Nutrition and Food Science
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• v.20 no.2
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• pp.83-87
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• 2015

Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-${\alpha}$, interleukin-(IL)-$1{\beta}$, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-${\alpha}$, IL-$1{\beta}$, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-$1{\beta}$, TNF-${\alpha}$, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.191-197
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• 2019

Sepsis, an infectious disease, is a life-threatening condition that arises when the response to infection causes injury to tissues and organs. The purpose of this study was to demonstrate whether ABHC-1 and ABHC-2, two functional extracts from herbal complex, have an anti-bacterial effect against Escherchia coli in vivo, in vitro experimental model. ABHC-1 and ABHC-2 showed the antibacterial activity against the bacteria by paper disc method. The minimum inhibitory concentration (MIC) was measured using alamar blue reagent. The MIC was shown at $60{\mu}g/ml$ from ABHC-1 and $500{\mu}g/ml$ from ABHC-2 against E. coli. We next examined the effect of ABHCs on the production of inflammatory cytokine, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), which is related to the induction of inflammation, in RAW 264.7 cell. ABHC-1 and ABHC-2 increased $TNF-{\alpha}$ production of RAW 264.7 cell in a dose-dependent manner while two extract decreased $TNF-{\alpha}$ production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell in a dose-dependent manner. At a dose of $1{\times}10^8$ E. coli. i.p., non-treated mice were succumbed, while most of mice treated with ABHC-1 were survived. Therefore, our results suggest that ABHC-1 has anti-bacterial activity and can be a novel therapeutic agent against infectious diseases.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.234-241
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• 2009

Purpose : We investigated the relationship between thyroid hormone and serum tumor necrosis factor (TNF-${\alpha}$), interleukin (IL-6) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in patients with Kawasaki disease (KD). Methods : Serum levels of thyroid hormone, TNF-${\alpha}$, IL-6, and NT-proBNP were measured in 52 KD patients in the acute and subacute phase and 10 patients with acute febrile illness (control group). TNF-${\alpha}$ and IL-6 were determined by sandwich enzyme-linked immunosorbent assay (ELISA). Echocardiography was performed to detect coronary artery lesions (CAL) in KD patients. Results : Low $T_3$ syndrome occurred in 63.5% of KD patients. $T_3$ in the acute phase of KD was lower than that in the control. In KD patients, $T_3$ was lowered in the acute phase and elevated in the subacute phase, whereas TNF-${\alpha}$, IL-6 and NT-proBNP were elevated in the acute phase and decreased in the subacute phase. NT-proBNP, and IL-6 were higher in patients with low $T_3$ than in those with normal $T_3$. In addition, $T_3$ inversely correlated with IL-6 and NT-proBNP. Of the 4 patients with CAL, 3 had very low $T_3$. Compared with intravenous immunoglobulin (IVIG)-responsive patients, IVIG-resistant patients had lower $T_3$ and higher IL-6 and NT-proBNP. Conclusion : $T_3$ decreases in the acute phase of KD and normalizes in the subacute phase without thyroid hormone replacement. Low $T_3$ may be partially induced by IL-6 rather than TNF-${\alpha}$, and is strongly associated with high NT-proBNP. $T_3$ in KD may be used for the differential diagnosis, monitoring the activity of the disease, and predicting the severity of inflammation.

• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.11-18
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• 2006

Certain flavonoids possess anti-inflammatory activity. Besides their antioxidative property, the cellular action mechanisms of flavonoids include an inhibition of arachidonate metabolizing enzymes such as cyclooxygenases and lipoxygenases, and a down-regulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-$\alpha$. In this review, the recent findings of anti-inflammatory flavonoid research since 2004 were summarized. And the cellular mechanisms on signal transduction pathways were also discussed.