• 약학회지
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• 제47권5호
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• 한국발생생물학회지:발생과생식
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• 제21권1호
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• pp.35-46
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• 2017

The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.

• 동의생리병리학회지
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• 제23권3호
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• pp.673-677
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• 2009

In order to verify the anti-inflammatory effects of Gelidium amansii, RAW264.7 macrophages were incubated with the extract of 70% ethanol solution (Ex), and activated with the endotoxin lipopolysaccharide (LPS). Ex inhibited the expression of the pro-inflammatory enzymes, including inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of iNOS-mediated NO and COX-2-mediated prostglandin $E_2$ ($PGE_2$) production in a dose-dependent manner. Ex also reduced the release of the pro-inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-1${\beta}$ (IL-1${\beta}$) and IL-6 in LPS-activated macrophages, The observed anti-inflammatory effects of Ex was associated with inactivation of the nuclear factor ${\kappa}B$ (NF-${\kappa}B$) that mediates the induction of iNOS, COX-2, TNF-${\alpha}$, IL-1${\beta}$, and IL-6. Further studies showed that Ex inactivated NF-${\kappa}B$ through inhibition of phosphorylation of the inhibitory ${\kappa}B$ ($l{\kappa}B$), Taken together, these results suggest that Gelidium amansii exerts anti-inflammatory effects by inhibiting the expression of pro-inflammatory enzymes and the secretion of pro-inflammatory cytokines via inactivation of NF-${\kappa}B$ and/or $l{\kappa}B$.

• Archives of Pharmacal Research
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• 제26권5호
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• pp.383-388
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• 2003

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity ($IC_{50} = 13.1 \mu$ g/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and BF-3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-$\alpha and IL-1\beta$ are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-$\alpha and IL-1\beta$ production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-$\alpha and IL-1\beta$production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-$\alpha and IL-1\beta$) production.

• 치위생과학회지
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• 제19권4호
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• pp.254-260
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• 2019

Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

• 생물정신의학
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• 제15권3호
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• pp.175-185
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• 2008

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

• 대한의생명과학회지
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• 제21권4호
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• pp.218-226
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• 2015

The present study investigated the mechanisms of licochalcone B (LicB)-mediated inhibition of the inflammatory response in murine macrophages. RAW264.7 murine macrophages were cultured in the absence or presence of lipopolysacharide (LPS) with LicB. LicB suppressed the generation of nitric oxide and the pro-inflammatory cytokines interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor-${\alpha}$. LicB also inhibited the expression of mRNA for inducible nitric oxide synthase and pro-inflammatory cytokines induced by LPS. Moreover, LicB inhibited nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 translocation into the nucleus in a dose-dependent manner. Thus, LicB mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-${\kappa}B$ and activator protein-1 signaling pathways in macrophages, which subsequently diminishes the expression and release of various inflammatory mediators. LicB shows promise as a therapeutic agent in inflammatory diseases.

• IMMUNE NETWORK
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• 제9권3호
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• pp.98-105
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• 2009

Background: It has been recently noticed that type 2 diabetes (T2D), one of the most common metabolic diseases, causes a chronic low-grade inflammation and activation of the innate immune system that are closely involved in the pathogenesis of T2D. Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. The molecular mechanisms of cordycepin in T2D are not clear. In the present study, we tested the role of cordycepin on the anti-diabetic effect and anti-inflammatory cascades in LPS-stimulated RAW 264.7 cells. Methods: We confirmed the levels of diabetes regulating genes mRNA and protein of cytokines through RT-PCR and western blot analysis and followed by FACS analysis for the surface molecules. Results: Cordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as $11{\beta}$-HSD1 and PPAR${\gamma}$ were decreased as well as expression of co-stimulatory molecules such as ICAM-1 and B7-1/-2 were also decreased with the increment of its concentration. In accordance with suppressed pro-inflammatory cytokine production lead to inhibition of diabetic regulating genes in activated macrophages. Cordycepin suppressed NF-${\kappa}B$ activation in LPS-activated macrophages. Conclusion: Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-${\kappa}B$ dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

• Journal of Applied Biological Chemistry
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• 제56권4호
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• pp.249-255
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• 2013

Recently, algae has been considered as a potential anti-inflammatory source due to its distinctive habitat environment exposing to light and high oxygen concentration. In present study, anti-inflammatory effect of brown alga, Sargassum fullvellum ethanol extract (SFEE), was examined. SFEE inhibited not only the production of nitric oxide and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) but also the expression of inducible nitric oxide synthase and cyclooxygenase 2 in LPS-induced RAW 264.7 cells without affecting cell viability. SFEE also suppressed the expression of nuclear factor kappa B (NF-${\kappa}B$), suggesting that SFEE could affect the expression of inflammation related cytokines and proteins through the regulation of NF-${\kappa}B$. Furthermore, formation of edema of the ear was 40% lower in mice treated with the highest dose (250 mg/kg) of SFEE than in the control mice. Thus, our study showed that SFEE may be a potential therapeutic anti-inflammatory drug.

• 대한한의학회지
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• 제32권6호
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• pp.18-29
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• 2011

Objectives: To investigate anti-inflammatory and anti-arthritic effects of Gyulpidaehwangbakcho-tang (GDBT) extract in a murine model of rheumatoid arthritis. Methods: The mice received $100{\mu}g$ of bovine type II collagen in Freund's complete adjuvant by intradermal injection at the base of the tail on day 0 and a booster injection on day 21. The mice were orally administered with GDBT (200 or 50mg/kg dissolved in distilled water) daily from day 1 to day 21 after arthritis incidence, and monitored for disease incidence and the severity of arthritis up to day 21. In order to evaluate the effect of GDBT on disease progression, we examined pro-inflammatory cytokines including IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II. Results: GDBT produced a significant and dose dependent inhibition of arthritis and inflammation during the entire duration of the study. This action was characterized by the decreased production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, and NOS-II in vivo. Conclusion: We believe that the anti-arthritic activity of GDBT is due to its modulatory effect on the expression of pro-inflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of GDBT in the treatment of RA and other inflammatory joint disorders.