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

• YAKHAK HOEJI
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• v.54 no.6
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• pp.500-506
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• 2010

TNF-${\alpha}$ and VCAM-1 play a pivotal role in the pathogenesis of rheumatoid arthritis, and the development of drugs targeting these molecules has extended the therapeutical approaches to rheumatoid arthritis patients. Bispecific antibodies combine the antigen-binding sites of two antibodies within a single molecule and thus they are able to bind to two different epitopes simultaneously. A specific bispecific antibody format termed "Di-diabody" was made for the efficient approach to anti-inflammation. In this study, the DNA vector construct of Di-diabody was built up against two antigens, VCAM-1 and TNF-${\alpha}$. For evaluating this Di-diabody as a bispecific antibody on the efficacy of anti-inflammation, the proteins were analyzed according to each antigen binding affinity and cell based assay related separate molecules. The 7H/Humira Di-diabody produced in this study interacted with its ligands, VCAM-1 and TNF-${\alpha}$, respectively. Also, this antibody exhibited the similar functional activities as compared to 7H-IgG in respect to inhibition of hVCAM-1-induced cell adhesion and Humira-IgG in respect to inhibition of TNF-${\alpha}$ induced cytotoxicity. Further study to elucidate the pharmacological significance of the Di-diabody is warranted using experimental animals.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.4
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• pp.220-225
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• 2017

Lithospermi Radix (LR) is known to have an anti-inflammatory effect. However, the mechanisms are not well known. In this study, LPS-induced mouse RAW 264.7 macrophage cells were treated with LR to investigate the time-dependent inflammation response of LR. RAW 264.7 cells were treated with various concentrations of LR for 24 hours, followed by MTS assay. Cell viability was increased at all experimental concentrations. The mRNA expression levels of $IL-1{\beta}$, $TNF-{\alpha}$ and iNOS were increased by treatment of RAW 264.7 cells with LR at a concentration of $200{\mu}g/ml$ for 6 hours and 24 hours. Treatment of LR with $200{\mu}g/ml$ concentration for 6 hours promoted mRNA expression levels of $IL-1{\beta}$, $TNF-{\alpha}$ and iNOS in LPS-induced RAW 264.7 cells. However, $IL-1{\beta}$, $TNF-{\alpha}$ and iNOS mRNA expression was suppressed by treatment of LR with $200{\mu}g/ml$ concentration for 24 hours in LPS-induced RAW 264.7 cells. These results suggest that the effect on inflammation of LR is promptly promoted and then to rapidly alleviate the inflammatory reaction. This study proposes that the time-dependent activities of herbal medicine is a very important factor in analyzing the anti-inflammatory effect of various herbal medicines including LR.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.146-152
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• 2012

Panax ginseng (PG) is a globally utilized medicinal herb. The medicinal effects of PG are primarily attributable to ginsenosides located in the root and leaf. The leaves of PG are known to be rich in various bioactive ginsenosides, and the therapeutic effects of ginseng extract and ginsenosides have been associated with immunomodulatory and anti-inflammatory activities. We examined the effect of PG leaf extract and the isolated ginsenosides, on nuclear factor (NF)-${\kappa}B$transcriptional activity and target gene expression by applying a luciferase assay and reverse transcription polymerase chain reaction in tumor necrosis factor (TNF)-${\alpha}$-treated hepatocarcinoma HepG2 cells. Air-dried PG leaf extract inhibited TNF-${\alpha}$-induced NF-${\kappa}B$transcription activity and NF-${\kappa}B$-dependent cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) gene expression more efficiently than the steamed extract. Of the 10 ginsenosides isolated from PG leaves, Rd and Km most significantly inhibited activity in a dose-dependent manner, with $IC_{50}$ values of $12.05{\pm}0.82$ and $8.84{\pm}0.99\;{\mu}M$, respectively. Furthermore, the ginsenosides Rd and Km inhibited the TNF-${\alpha}$-induced expression levels of the COX-2 and iNOS gene in HepG2 cells. Air-dried leaf extracts and their chemical components, ginsenoside Rd and Km, are involved in the suppression of TNF-${\alpha}$-induced NF-${\kappa}B$ activation and NF-${\kappa}B$-dependent iNOS and COX-2 gene expression. Consequently, air-dried leaf extract from PG, and the purified ginsenosides, have therapeutic potential as anti-inflammatory.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.4
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• pp.49-68
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• 2008

Purpose: This study was performed to evaluate anti-inflammatory effects of Cheongyeoljohyeoltangkamibang water extract (CYJHT). Methods: In the study of anti-inflammatory effects. CYJHT was investigated using cultured cells and murine models. As for the parameters of inflammation. levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells(mLFCs). RAW 264.7 cells and acute inflammation-induced mice. Results: 1. CYJHT showed a safety in cytotoxicity and toxicity of liver. 2. CYJHT effected scavenging activity on 2.2-diphenyl-1-picrylhydrazyl(DPPH) free radical, superoxide dismutase(SOD) and superoxide anion radical(SAR). 3. CYJHT in RAW 264.7 cell decreased IL-l$\beta$ mRNA expression at 100, 50 ${\mu}g$/ml and also decreased TNF-$\alpha$ mRNA expression at 100 ${\mu}g/ml$ and decreased COX-2. NOS-II mRNA expression and decreased IL-6 mRNA expression in a concentration-dependent manner. 4. CYJHT in RAW 264.7 cell decreased IL-l$\beta$ significantly at 100, 50 ${\mu}g$/ml and decreased IL-6. TNF-$\alpha$ significantly at 100 ${\mu}g$/ml. 5. CYJHT inhibited IL-l1$\beta$, IL-6 and TNF-$\alpha$ production significantly in serum of acute inflammation-induced mice. 6. CYJHT decreased IL-1$\beta$, IL-6 and TNF-$\alpha$ mRNA production significantly in spleen tissue. and also decreased IL-l$\beta$. TNF-$\alpha$ mRNA production significantly in liver tissue of acute inflammation-induced mice. Conclusion: These results suggest that CYJHT can be useful in treating diverse female diseases caused by inflammation such as menstrual pain. menstrual disorder. leukorrhea. pelvic inflammatory disease and so on.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.2
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• pp.1-15
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• 2021

Objectives: This study was designed to examine immuno-modulatory effects of Evodia Rutaecarpine by activating innate immune system and inhibiting inflammation. Methods: First, Cell cytotoxicity was examined with 4T1 breast carcinoma and TG-induced macrophage. To investigate activating innate immune system of Evodiamine Rutacarpine Extract (ERE) on macrophage, we tested tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with ERE to observe innate immune modulating effect of ERE on RAW 264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In cytotoxicity analysis, ERE significantly affected tumor cell growth above specific concentration. Also, ERE significantly affected macrophage growth above specific concetration. As compared with the control group, the production of TNF-α, IL-12 and IL-6 were increased in TG-induced macrophage. As compared with the control group, TNF-α and IL-6 were significantly up-regulated in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating ERE was significantly decreased compared with control group. In addition, We observed ERE inhibited the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38 in western blotting by treating ERE on RAW 264.7 cell. Conclusions: ERE seems to have considerable impact on the anti-cancer effect by activation of innate immune system and inflammation control.

• IMMUNE NETWORK
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• v.24 no.1
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• pp.4.1-4.19
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• 2024

TNF, a pleiotropic proinflammatory cytokine, is important for protective immunity and immunopathology during Mycobacterium tuberculosis (Mtb) infection, which causes tuberculosis (TB) in humans. TNF is produced primarily by phagocytes in the lungs during the early stages of Mtb infection and performs diverse physiological and pathological functions by binding to its receptors in a context-dependent manner. TNF is essential for granuloma formation, chronic infection prevention, and macrophage recruitment to and activation at the site of infection. In animal models, TNF, in cooperation with chemokines, contributes to the initiation, maintenance, and clearance of mycobacteria in granulomas. Although anti-TNF therapy is effective against immune diseases such as rheumatoid arthritis, it carries the risk of reactivating TB. Furthermore, TNF-associated inflammation contributes to cachexia in patients with TB. This review focuses on the multifaceted role of TNF in the pathogenesis and prevention of TB and underscores the importance of investigating the functions of TNF and its receptors in the establishment of protective immunity against and in the pathology of TB. Such investigations will facilitate the development of therapeutic strategies that target TNF signaling, which makes beneficial and detrimental contributions to the pathogenesis of TB.

• Journal of the Korean Chemical Society
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• v.65 no.1
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• pp.15-24
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• 2021

In this study, the extract of Cinnamomum yabunikkei leaves were investigated for the anti-inflammatory and anti-oxidative activities and their active constituents were identified. In the anti-inflammatory tests using LPS-stimulated RAW 264.7 cells, the ethyl acetate (EtOAc) fraction inhibited the production of nitric oxide (NO) without causing cell toxicity. In addition, the EtOAc fraction reduced expression of iNOS protein and production of pro-inflammatory cytokines (TNF-α, IL-1β). Upon the anti-oxidative studies by DPPH and ABTS+ radicals, potent radical scavenging activities were observed in the EtOAc fraction. Five phytochemicals were isolated from the extract of C. yabunikkei leaves; (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-enone (1), methoxy-(3,5-dimethoxy-4-hydroxyphenyl)ethanediol (2), afzelin (3), nicotiflorine (4) and narcissin (5). As far as we know, compounds 1-5 were isolated for the first time from this plant. In the anti-inflammatory tests for the isolates, compound 1, 3, 4 and 5 were determined to decrease NO production without causing cell toxicity. Furthermore, compound 1 reduced expression of iNOS protein and exhibited potent inhibitory activities of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Based on these results, it was suggested that the extract and isolated compounds from C. yabunikkei leaves could be potentially applicable as natural source for pharmaceutical and/or cosmetic ingredients.

• Journal of Life Science
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• v.25 no.12
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• pp.1377-1383
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• 2015

Scopoletin is a component of several plant such as Erycibe obtusifolia, Aster tataricus, Foeniculum vulgare and Brunfelsia grandiflora. It was reported to have anti-angiogenesis and anti-allergy effects. In this study, the anti-inflammatory effect of scopoletin was investigated in Raw264.7 cells, mouse macrophages. The effects of scopoletin on phagocytosis and nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced inflammatory responses. It was observed that scopoletin exerted inhibitory effects on both phagocytosis and NO production. In addition, scopoletin decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) which were related to NO and prostaglandin E2 (PGE2) production. In particular, the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression levels of IL-1β, IL-6 were remarkably decreased by treatment with scopoletin. Furthermore, the content of TNFα produced by macrophage was decreased in the presence of scopoletin at 8 hr. These results indicate that the anti-inflammatory effect of scopoletin could exert by inhibiting the expression of pro-inflammatory cytokines in Raw264.7 cells stimulated with LPS. The above results suggest scopoletin could be a new remedial agent for anti-inflammation through inhibition of iNOS, COX-2, IL-1β, IL-6 and TNF-α expressions as well as supression of phagocytosis and NO production.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.2
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• pp.1-15
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• 2011

Objective : Recently interest of fermented herb medicine has increased in Oriental medicine. Herb medicine fermented in a proper condition resultingly has better or new virtue by microbe. This study was designed to compare the anti-inflammatory effects of herbal decoction and fermented herbal decoction in Hwangnyeonhaedok-tang (Huanglian fiedu-tang; HHT). Methods : The effects of HHT and FHHT on anti-inflammation were measured by production of NO and pro-inflammatory cytokine productions including TNF-${\alpha}$ and IL-1${\beta}$, IL-6 in LPS induced RAW 264.7 cells. Results : 1. Cell viability in three doses of HHT extract (0.01, 0.05 and 0.10 mg/ml) and two doses of FHHT extract (0.01, 0.05 mg/ml) was more than 70％ and 80％ each. 2. In RAW 264.7 cells, LPS displayed significant stimulatory effects on the production of NO. However, both HHT, FHHT showed significant inhibitory effects on the production of NO. 3. Pre-treatment by HHT in a various concentrations (0.01, 0.05, 0.10, 0.50mg/ml) reduced the elevated production of TNF-${\alpha}$, IL-1${\beta}$, IL-1${\beta}$ mRNA, IL-6 mRNA. More than 0.05mg/ml concentrations of HHT reduced the production of IL-6. And TNF-${\alpha}$, IL-1${\beta}$ level of mouse serum reduced in a various dose(0.1, 0.5, 1.0g/kg). 4. Pre-treatment by FHHT in a various concentrations (0.01, 0.05, 0.10, 0.50mg/ml) reduced the elevated production of TNF-${\alpha}$. More than 0.05mg/ml concentrations of FHHT reduced the expression of TNF-${\alpha}$ mRNA. 0.1, 0.50mg/ml concentrations of FHHT reduced the production of IL-6. And IL-1${\beta}$ level of mouse serum reduced in a various dose(0.1, 0.5, 1.0g/kg). Conclusions : These results indicated that both HHT and FHHT could have anti-inflammatory capacity by inhibiting the production of NO and cytokines in vitro. But HHT has more strong anti-inflammatory effects than that of FHHT in broad outlines.