• The Korea Journal of Herbology
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• v.22 no.4
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• pp.109-116
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• 2007

Objectives : In the present study, we investigated anti-inflammatory effects of chloroform fraction of Coptidis rhizoma (CR-C) on the production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines, tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin-1beta (IL-1${\beta}$) in LPS-stimulated BV2 microglial cells. Methods : Copriditis rhizoma was extracted with 80% methanol, and then extracted with chloroform. BV2 cells were pre-treated with CR-C, and stimulated with LPS. The cytotoxicity was determined by MTT assay. The production of NO and cytokines was measured by Griess assay and ELISA. The mRNA expression of inducible nirtic oxide synthase (iNOS) and cytokines were determined by RT-PCR. Results : CR-C significantly inhibited the production of NO. TNF-${\alpha}$ and IL-1${\beta}$ in a dose-dependent manner in LPS-stimulated BV2 cells. In addition, CR-C suppressed the mRNA expressions of iNOS and inflammatory cytokines induced by LPS stimulation. These results indicate that CR-C was involved in anti-inflammatory effects in activated microglia. Conclusion : The present study suggests that chloroform extract of Coptidis rhizoma can be useful as a potential anti-inflammatory agent for treatment of various neurodegenerative diseases.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.268-282
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• 2016

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

• Advances in Traditional Medicine
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• v.10 no.1
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• pp.37-43
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• 2010

Palmitic acid (PA) is one of free fatty acids, which is found from Gaultheria itoana Hayata and Sarcopyramis nepalensis. Although PA has a variety of pharmacological effects including mediates hypothalamic insulin resistance, induces IP-10 expression, and promote apoptotic activities, the anti-inflammatory mechanism of PA in mouse peritoneal macrophages remains unclear. In this study, we showed that PA exerted an anti-inflammatory action through suppression the production of tumor necrosis factor-$\alpha$, interleukin-6, cyclooxygenases-2 and nitric oxide in lipopolysaccaride-stimulated mouse peritoneal macrophages. Our study suggests an important molecular mechanism of PA, which might explain its beneficial effect in the regulation of inflammatory reactions.

• IMMUNE NETWORK
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• v.9 no.1
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• pp.12-19
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• 2009

Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.17 no.1
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• pp.163-171
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• 2004

The flowers of Lonicera japonica Thunb. (Caprifoliaceae) has been used as anti-inflammatory drug in the folk medicine recipe and been proved its anti-inflammatory effect in the oriental medicine. However, the action mechanism of Lonicera japonica that exhibits anti-inflammatory effects has not been determined. Since nitric oxide (NO) is one of the major inflammatory parameter, we studied the effect of aqueous extracts of Lonicera japonica (AELJ) on NO production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. NO and inducible NO synthase (iNOS) level were significantly reduced in LPS-stimulated macrophages by AELJ compared to those without Electrophoretic mobility shift assay (EMSA) indicated that AELJ blocked the activation of nuclear factor kappa B (NF-kB), which was considered to be a potential transcription factor for the iNOS expression. AELJ also blocked the phosphorylation and degradation of inhibitor of kappa B-alpha (IkB-${\alpha}$). Furthermore, IkB kinase alpha (IKK${\alpha}$), which is known to phosphorylate serine residues of IkB directly, is inhibited by AELJ in vivo and in vitro. These results suggest that AELJ could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of NF-kB activity.

• Natural Product Sciences
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• v.21 no.4
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• pp.240-247
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• 2015

Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 ($PGE_2$) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B ($NF-{\kappa}B$) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B $(I{\kappa}B)-{\alpha}$ in the cytoplasm, and suppressed the translocation of $NF-{\kappa}B$ p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of $NF-{\kappa}B$ in LPS-stimulated RAW264.7 and BV2 cells.

• The Korea Journal of Herbology
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• v.34 no.1
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• pp.51-57
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• 2019

Objectives : Nypa fruticans Wurmb. (NF) have been used as a traditional medicine to treat inflammatory diseases in East-South Asia. However, it is largely undiscovered whether NF water extract could exhibit anti-inflammatory activities against tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced inflammatory responses on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the anti-inflammatory activity of NF water extract on TNF-${\alpha}$-induced inflammatory responses in HaCaT cells. Methods : To investigate the anti-inflammatory activites of NF water extract in HaCaT cells, the inflammatory model of HaCaT cells was established under a suitable concentration (10 ng/ml) of human TNF-${\alpha}$ (hTNF-${\alpha}$). HaCaT keratinocyte cells were pre-treated with NF water extract for 1 h, and then stimulated with hTNF-${\alpha}$. Then, the cells were harvested to measure the inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin $E_2$ ($PGE_2$), and pro-inflammatory cytokine including TNF-${\alpha}$ and interleukin (IL)-6. In addition, we examined the inhibitory mechanisms of NF, mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha ($I{\kappa}-B{\alpha}$) Results : The treatment of NF inhibited the hTNF-${\alpha}$-induced elevation of iNOS, COX-2, and $PGE_2$ in HaCaT cells. In addition, NF treatment inhibited the hTNF-${\alpha}$-induced elevation of TNF-${\alpha}$ and IL-6. Furthermore, NF treatment inhibited the activation of MAPKs but not degradation of $I{\kappa}-B{\alpha}$. Conclusions : Taken together, our result suggest that treatment of NF could inhibit the hTNF-${\alpha}$-induced inflammatory responses via deactivation of MAPKs in HaCaT cells. This study could suggest that NF could be a beneficial agent to prevent skin damage or inflammation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.4
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• pp.329-335
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• 2018

Loss of response to anti-tumor necrosis factor (anti-TNF) agents in the treatment of inflammatory bowel disease (IBD) is a major consideration to maintain sustained response. Reversal of immunogenicity can re-establish response and increase the durability of these agents. Strategies to reverse immunogenicity include dose-intensification and/or the addition of an immunomodulator. However, there is a relative paucity of data on the efficacy of such interventions in pediatric IBD patients. Available reports have not strictly utilized homogenous mobility shift assay, which reports on anti-drug antibodies even in the presence of detectable drug, whereas prior studies have been confounded by the use of drug sensitive assays. We report four pediatric inflammatory bowel disease patients with successful reversal of immunogenicity on an anti-TNF agent using dose intensification and/or addition of an immunomodulator.

• Journal of Applied Biological Chemistry
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• v.62 no.2
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• pp.111-122
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• 2019

The mulberry tree (Morus alba L.) has been traditionally used in Chinese medicine to treat inflammatory diseases. We investigated the effects of bioconversion on different components of the mulberry tree, and determined changes in the physiological activities. Ethyl acetate-soluble fractions of five different segments (fruit, Mori Fructus; leaf, Mori Folium; twig, Mori Ramulus; root, Mori Cortex; and mistletoe, Loranthi Ramulus) of the mulberry tree show enhanced anti-oxidant effects in the 2,2-diphenyl-1-picrylhydrazyl, and 2,2'-azinobis-(3-ethylvenzothiazoline-6-sulfonic acid) assays, and enhanced anti-inflammatory effects of lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 macrophages, after being treated with a crude enzyme extract from Aspergillus kawachii, in the following order of activity: Mori Folium>Mori Cortex>Mori Ramulus>Mori Fructus>Loranthi Ramulus. Ethyl acetate- soluble fraction of mulberry leaves (Mori Folium) that underwent bioconversion was most effective, and was devoid of any cytotoxicity. The fraction was also effective against mRNA expression of LPS-induced pro-inflammatory cytokines, such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and interleukin-6. In addition, the fraction was effective in LPS-induced phosphorylation of mitogen-activated protein kinases and IKK, and $I{\kappa}B$ degradation, followed by translocation of the nuclear $factor-{\kappa}B$ from the cytoplasm to the nucleus. Thus, bioconversion increased the anti-oxidative and anti-inflammatory activities of the mulberry leaf.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.60-65
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• 2013

3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-${\alpha}$, and IL-$1{\beta}$. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.