• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3307-3312
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• 2014

The anti-inflammatory effect of a tubulin inhibitor, N-(5-benzyl-1,3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide (1), on innate immune responses remains unclear. Thus, we investigated the effect of 1 on the immune responses mediated by lipopolysaccharide (LPS). The in vitro addition of 1 to dendritic cells and macrophages dose-dependently reduced tumor necrosis factor alpha production elicited by LPS stimulation. Additionally, the stimulation of natural killer (NK) and natural killer T (NKT) cells with 1 resulted in the decrease of interferon gamma ($IFN{\gamma}$) induced by LPS treatment. Moreover, 1 substantially reduced interleukin 12 in dendritic cells (DC) as well as $IFN{\gamma}$ in NKDCs induced by LPS in vitro. Furthermore, the in vivo administration of 1 ameliorated LPS/D-galactosamine-induced endotoxic lethality in mice. Taken together, our results demonstrate for the first time that 1 possesses anti-inflammatory properties, most notably by modulating LPS-induced innate immune responses. Therefore, 1 might have therapeutic potential for the treatment of inflammation-mediated diseases such as sepsis.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.159-164
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• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1220-1225
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• 2004

The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is known to be responsible for vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. In the course of screening oriental anti-inflammatory herbs for the inhibitory activity of NO synthesis, a crude methanolic extract of Curcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc soluble fraction allowed us to isolate three active compounds. They were identified as 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analyses. Their concentrations for the 50% inhibition of NO production $(IC_{50})$ in lipopolysaccharide (LPS)-activated macrophages were 8, 75, 77 ${\mu}M$, respectively. Compound 1 showed the most potent inhibitory activity for NO production in LPS-activated macrophages, while the epimeric isomers, compound 2 and 3 showed weak and similar potency. Inhibition of NO synthesis by compound 1 was very weak when activated macrophages were treated with 1 after iNOS induction. In the immunoblot analysis, compound 1 suppressed the expression of iNOS in a dose-dependent manner. In summary, 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one from Curcuma zedoaria inhibited NO production in LPS-activated macrophages through suppression of iNOS expression. These results imply that the traditional use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by inhibition of NO production.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.150-162
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• 2009

Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.141-148
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• 2022

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.11-19
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• 2024

Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.428-434
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• 2024

Background: Platelet-leukocyte aggregates (PLAs) play important roles in cardiovascular disease and sepsis. Red ginseng extract (RGE) has been well-studied for its antiplatelet and anti-inflammatory activities. However, the potential inhibitory effects of RGE on PLA have not been investigated. Methods: Six-week-old ICR mice were given oral gavage of RGE for 7 days, followed by an intraperitoneal injection of 15 mg/kg of lipopolysaccharide. Mice were euthanized 24 h later, and blood samples were collected for further analysis. Flow cytometry was utilized to sort populations of PLAs and platelet-neutrophil aggregates (PNAs). By using confocal microscopy, PNAs were validated. Morphological changes in platelets and leukocytes were visualized with scanning electron microscopy. Expressions of tissue factor (TF) and platelet factor 4 (PF4) were investigated using enzyme-linked immunosorbent assay. Results: Populations of activated platelets, PLAs and PNAs, were significantly increased with LPS-induction. Treatment with 200 and 400 mg/kg of RGE decreased platelet activation. Moreover, the populations of PLAs and PNAs were reduced. PNAs were visible in the blood of septic mice, and this was attenuated by treatment with 400 mg/kg of RGE. Morphologically, sepsisinduced platelet activation and fibrin formation in the blood. This was reduced with RGE treatment. Sepsis-induced increase in the plasma levels of TF and PF4 was also reduced with RGE treatment. Conclusion: This study shows that RGE is a potential therapeutic that reduces the activation of platelets and targets PLA and PNA formation. Detailed inhibitory mechanisms of RGE should be studied.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.317-321
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• 2006

A case is reported of a man with malignant fibrous histiocytoma (MFH) in right thigh who developed streptococcal toxic shock syndrome (STSS) during postoperative radiotherapy. Before radiotherapy, a patient complained wax and wane lymphedema following wide excision of tumor mass which was confirmed as MFH. He took some nonsteroidal antiinflammatory drug (NSAID) for about one month. He suffered preexisting hepatitis C virus (HCV) infection, diabetes and well-controlled hypertension. The patient received conventional radiotherapy to right thigh with a total dose of 32.4 Gy at 1.8 Gy per day. At last radiotherapy fraction, cutaneous erythematous inflammation was suddenly developed at his affected thigh. At that time, he also complained of oliguria, fever and chills. The patient was consulted to internal medicine for adequate evaluation and management. The patient was diagnosed as suggested septic shock and admitted without delay. At admission, he showed hypotension, oliguria, constipation, abnormal renal and liver function. As a result of blood culture, Streptococcus pyogenes was detected. The patient was diagnosed to STSS. He was treated with adequate intravenous antibiotics and fluid support. STSS is one of oncologic emergencies and requires immediate medical intervention to prevent loss of life. In this patient, underlying HCV infection, postoperative lymphedema, prolonged NSAID medication, and radiotherapy may have been multiple precipitating factors of STSS.

• Journal of Chest Surgery
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• v.5 no.1
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• pp.45-56
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• 1972

Esophageal perforation is one of the most grave prognostic problems among thoracic and general surgical emergencies which necessitate urgent operative measures. In Korea,there are still many persons ingesting lye for suicidal attempt and thoracic surgeons in Korea have more chances to deal with lye burned esophagus with or without instrumental perforation than those in Western countries. Main cause of esophageal perforation in Korea is instrumental perforation in patients with lye stricture of the esophagus during diagnostic endoscopy or therapeutic bouginage. Other causes are corrosion of the esophagus due to ingestion of caustic agents, pathologic perforation, surgical trauma, stab wound and spontaneous rupture of the esophagus in our series. Therapeutic measures are various,and depend on duration of perforation, severity of its complications, pathology of perforated portion of the esophagus and degrees of inflammation at the point of perforation. The most important therapeutic measures are prevention of this grave condition during esophagoscopy, bouginage and surgical procedures on lungs and mediastinal structures and to make early diagnosis with prompt therapeutic measures. During the period of January, 1959, to December, 1971, the authors experienced 65 cases ofesophageal perforation including acquired esophagorespiratory fistula at Dept. of Chest Surgery, the National Medical Center in Seoul, and obtained following results in the series. 1. Female were 35 cases, and peak age incidence was 2nd and 3rd decades of life. 2. Among 65 cases, 43 were corrosive esophagitis or benign stricture of the esophagus due to caustic agents, 7 were patients with esophageal cancer. and there were 5 cases of esophageal perforation developed after pneumonectomy or pleuropneumonectomy. 3. Causes of perforation are instrumental perforation in 45, acute corrosion in 7, pathologic perforation in 7, surgical trauma in 3, stab wound in 2 cases, and one spontaneous rupture of the esophagus. 4. Most frequent sites of esophageal perforation were upper and mid thoracic esophagus, and 8 were cases with cervical esophageal perforation. 5. Complications of esophageal perforation were mediastinitis in 42, empyema or pneumothorax in 35, esophagorespiratory fistula in 12, retroperitoneal fistula or abscess in 5,pneumoperitoneum in 3, and localized peritonitis in 1 case. 6. Cases with malignant esophagorespiratory fistula were only 3 in the series which is predominant cause of acquired esophagorespiratory fistula in Western countries. 7. Various therapeutic measures were applied with mortality rate of 27.7% in the series. 8. In usual cases early treatment gave better prognosis, and least mortality rate in cases with perforation in mid thoracic esophagus. 9. Main causes of death were respiratory complications,acute hemorrhage with asphyxia, and septic complications. 10. Esophageal perforation developed after pneumonectomy gave more difficult therapeutic problems which were solved in only 1 among 5 cases.

• Archives of Plastic Surgery
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• v.34 no.1
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• pp.77-80
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• 2007

Purpose: Purpura fulminans is a rare but rapidly progressive, serious, often life-threatening disorder in childhood, which is complicated with septic shock or disseminated intravascular coagulopathy during acute infection. It occurs first as acute-onset petechial rash, and spreads rapidly into full thickness skin and soft tissue necrosis. In the past, it had high mortality rate, up to 80%, but recently, survival rate has increased due to early diagnosis, and rapid advancement of critical care and antibiotics. From our experiences of PF management, we would like to review the pathophysiology and suggest the surgical treatment guideline about meningococcal induced purpura fulminans. Methods: Two cases of purpura fulminans over the last 3 years were reviewed retrospectively about reconstructive management. After they were treated resuscitative management initially by the critical intensive care, reconstructive surgery was performed by plastic surgeon as soon as the patients were vitally and mentally stable. Results: There were 6 procedures in case 1, and 3 procedures in case 2. The mean delayed period from admission with sepsis to the first surgical debridement was 24 days and 42 days, respectively. Total hospitalization period was 103 days and 69 days, respectively. All of them were treated with debridement and split thickness skin graft, but delayed debridement was superior to early one in the point of preserving much more tissues. Conclusion: From our experience, we suggest that conservative therapy to the wounds appears to be the best tool in the initial vitally unstable period in order to preserve as much tissues and functions as possible if no active inflammation and compartment syndrome are detective.