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

• The Journal of Korean Obstetrics and Gynecology
• /
• v.21 no.2
• /
• pp.166-183
• /
• 2008

Purpose: This study was performed to determine anti-imflammatory effects of Haedoksamultang. Methods: In this study, I examined the effects of Haedoksamultang on the production of nitric oxide(NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), and interlukin-1${\beta}$(IL-1${\beta}$) as well as the expression of inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), TNF-${\alpha}$, and IL-1${\beta}$ in RAW 264.7 cells. Haedoksamultang inhibited LPS-stimulated NO production. Western blotting and RT-PCR analysis showed that Haedoksamultang suppressed LPS-induced iNOS and COX-2 protein and mRNA expression in RAW 264.7 cells. Haedoksamultang also suppressed the expression and production of LPS-stimulated TNF-${\alpha}$ and IL-1${\beta}$ in RAW 264.7 cells. Haedoksamultang inhibited NF-${\kappa}B$ activation in LPS-treated RAW 264.7 cells. Moreover, this compound blocked $I{\kappa}B-{\alpha}$ phosphorylation and nuclear translocation of the cytosolic NF-${\kappa}B$ p65 subunit, which highly correlated with the production and expression of inflammatory mediators. Results: Haedoksamultang suppresses that inflammation-associated gene expression by blocking NF-${\kappa}B$ activation. Conclusion: These results suggest that Haedoksamultang may be beneficial for treating inflammatory disease.

• Journal of Oriental Neuropsychiatry
• /
• v.10 no.1
• /
• pp.109-119
• /
• 1999

We investigated whether an aqueous extract of Chong-Myung-Tang inhibits secretion of tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$ from primary cultures of mouse astrocytes. Chong-Myung-Tang dosedependently inhibited the $TNF-{\alpha}$ secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). Interleukin-1 (IL-1) has been shown to elevate $TNF-{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore investigated whether IL-1 mediated inhibition of $TNF-{\alpha}$ secretion from astrocytes by Chong-Myung-Tang. Treatment of Chong-Myung-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS and SP. These results suggest that Chong-Myung-Tang may inhibits $TNF-{\alpha}$ secretion by inhibiting IL-1 secretion and that Chong-Myung-Tang has a antiinflammatory activity in the central nervous system.

• Journal of Haehwa Medicine
• /
• v.23 no.2
• /
• pp.5-13
• /
• 2015

Objectives : The anti-inflammatory and antioxidant effects of water extracts of Sasangja-tang(SSJ) and Gami-sasangja-tang(GSJ) were investigated. The effects of SSJ and GSJ were compared. Methods : We performed cell viability assay in HaCaT cells and RAW 264.7 cells using 3-(4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide(MTT) assay. We measured chemokines(regulated on activation normal T-cell expression and secreted ; RANTES/CCL5, interferon-inducible protein; IP-10/CXCL10, macrophage-derived chemokine; MDC/CCL22) in HaCat cells, also we measured cytokines (tumor necrosis factor-${\alpha}$; TNF-${\alpha}$, interleukin-6; IL-6) and nitric oxide(NO) production in RAW 264.7 cells using enzyme-linked immunosorbent assay(ELISA) and NO assay. Western blot assay was used to evaluate the expression for inducible nitric oxide synthase(iNOS) in RAW 264.7 cells. Results : SSJ and GSJ did not affect the cell viability at the concentrations treated ($0-800{\mu}g/ml$). As a result of SSJ and GSJ treatment in HaCat cells stimulated by TNF-${\alpha}$(10 ng/ml) and interferon(IFN)-${\gamma}$(10 ng/ml), the production of RANTES and IP-10 was inhibited significantly. However there was no significant difference in the secretion of MDC. And in RAW 264. 7 cells stimulated by lipopolysaccharide(LPS, $1{\mu}g/ml$), SSJ and GSJ treatment significantly inhibited the secretion of TNF-${\alpha}$ and IL-6 and the production of NO. The expression of iNOS was also decresed by SSJ and GSJ treatment in RAW 264. 7 cells. Compared with SSJ, GSJ was superior to SSJ in inhibition of RANTES, IP-10, TNF-${\alpha}$, IL-6 and NO production at the concentration of $200{\mu}g/ml$. Conclusion : Both SSJ and GSJ have anti-inflammatory and antioxidant effects. And GSJ has better effects than SSJ.

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.96-103
• /
• 2012

In the present study, the inhibitory effect of neem leaf extract (NLE) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production was examined both in vitro and in vivo. In vitro study revealed that NLE treatment ($100{\mu}g/ml$) inhibits LPS (100 ng/ml)-induced NO production by 96% and TNF-${\alpha}$ production by 32%. The reduction in NO production is probably conferred by the complete suppression of inducible nitric oxide synthase (iNOS) expression. Interestingly, in vivo NLE significantly improved the survival rate of mice in an experimental sepsis model. Administration of NLE (100 mg/kg) 24 h before LPS treatment (20 mg/kg) improved the survival rate of mice by 60%. The inhibition of plasma NO and TNF-${\alpha}$ production by NLE is likely to account for the improved survival of mice. Our results suggest that NLE may present a promising avenue in the development of therapeutic agents for the treatment of inflammatory diseases.

• Korean Journal of Medicinal Crop Science
• /
• v.15 no.5
• /
• pp.324-328
• /
• 2007

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

• The Korea Journal of Herbology
• /
• v.21 no.4
• /
• pp.59-67
• /
• 2006

Objectives : Sam-Myo-Whan(SMW) has been known traditional prescription with anti- anthritis activities. We investigated inhibitory effects of SMW on lipopolysaccharide (LPS)-induced nitric oxide(NO), $TNF-{\alpha}$ and inducible nitric oxide synthase(iNOS) production from RAW264.7 cells and BV-2 Microglia cells. Methods : SMW, which had been extracted with 70% MeOH, concentrated and freeze-dried was used for this experiment. After BV2 mouse brain macrophages and RAW264.7 mouse peritoneal macrophages were pretreated with increasing concentrations of SMW extract for 30min, and then activated with LPS. To investigate cytotoxicity of SMW extract, cell viability was measured by MTT assay. NO production was measured in each culture supernatant by Griess reaction. mRNA expression of iNOS in two type cells was investigated by RT-PCR. $TNF-{\alpha}$ production was measured in each culture supernatant by ELISA. Results : SMW extract significantly inhibited LPS-induced NO and $TNF-{\alpha}$ production in BV2 cells and RAW264.7 cells dose-dependently. SMW extract also greatly suppressed mRNA expression of iNOS in both type cells activated with LPS. Conclusion : These data suggests that SMW extract may have an anti-inflammatory effect through the inhibition of iNOS expression.

• Journal of Applied Biological Chemistry
• /
• v.55 no.4
• /
• pp.221-225
• /
• 2012

The anti-inflammatory effects of Undaria pinnatifida water extract (UPWE) were investigated using lipopolysaccharide-induced inflammatory response in this study. To examine the potential anti-inflammatory properties of UPWE, the cell proliferation, nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-${\alpha}$) and IL-$1{\beta}$ were measured. As a result, there was no cytotoxicity in the macrophage proliferation treated with UPWE compared to the control. NO levels decreased with increasing concentration of UPWE. Moreover, the secretion of IL-6, TNF-${\alpha}$ and IL-$1{\beta}$ were suppressed in a dose-dependent manner, and IL-6 inhibition activities were over 50% at 0.1%. These results suggested that UPWE may have significant effects on inflammatory factors and be a potential anti-inflammatory therapeutic materials.

• Journal of Oriental Neuropsychiatry
• /
• v.12 no.1
• /
• pp.137-149
• /
• 2001

Cytokines are polypeptides which possess various biological properties affecting. host defense function and response to disease. Inflammatory cytokines, tumor necrosis $factor-{\alpha}$(TNF-${\alpha}$), interleukin(IL)-1 and IL-6 induce inflammation, fever, hypotension and pain when injected into animals or human subject. When glial cell cultures were prepared from neonatal mice or rats, astrocytes were reported to produce these inflammatory cytokines to viral infection, lipopolysaccharide(LPS), or cytokines. The purpose of this study was to investigate the regulatory effect of these cytokines secretion from primary cultures of rat astrocytes. Substance P(SP) can stimulate secretion of TNF-${\alpha}$ from astrocytes stimulated with LPS. Sesim-Tang significantly inhibited the TNF-${\alpha}$ secretion by astrocytes stimulated with SP and LPS. IL-1 has been shown to elevate TNF-${\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of TNF-${\alpha}$ secretion from primary astrocytes by Sesim-Tang. Treatment of Sesim-Tang to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of TNF-${\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Furthermore Sesim-Tang inhibited the IL-6 secretion by astrocytes stimulated with SP and LPS. The inhibitory effect of inflammatory cytokines by Sesim-Tang, observed in this study, might reflect an antiinflammatory activity and a reduction of various-type pains, fever etc. in the central nervous system.

• The Journal of Korean Medicine
• /
• v.26 no.1 s.61
• /
• pp.59-70
• /
• 2005

Objective: Tumor necrosis factor-a $(TNF-{\alpha})$, a potent immuno-modulator and pro-inflammatory cytokine, has been implicated in many pathological processes. In this study, the author examined whether promoter region polymorphism in the $TNF-{\alpha}$a gene at position-308 affect the odds of cerebral infarction (CI) and whether genetic risk is enhanced by sasang constitutional classification. Methods: 212 CI patients and 610 healthy controls were genotyped and determined according to sasang constitutional classification. The amplified genotypes were analyzed on $8\%$ polyacrylamide gel. The alleles were visualized by ethidium bromide staining. Primers for $TNF-{\alpha}$ were designed to incorporate a polymorphic site at a position -308 bp of the $TNF-{\alpha}$ gene into an NcoI restriction site. Restriction digests generated products of 87 and 20 bp for G allele and 107 bp for A allele. Results : A significant decrease was found for the $TNF-{\alpha}$ A allele in CI patients compared with controls (P=0.033, odds ratio, O.R.: 0.622). However, there was no significant association between $TNF-{\alpha}$ polymorphism and sasang constitution in CI patients. Conclusion: My finding suggests that $TNF-{\alpha}$promoter region polymorphism is responsible for susceptibility to CI in Koreans.