• Biomolecules & Therapeutics
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• 제19권3호
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• pp.331-335
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• 2011

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.519-527
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• 2017

Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of balanophonin. The results indicated that balanophonin reduced not only the LPS-mediated TLR4 activation but also the production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), $Interleukin-1{\beta}$ ($IL-1{\beta}$), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), in BV2 cells. Balanophonin also inhibited LPS-induced inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) protein expression and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK. Interestingly, it also inhibited neuronal cell death resulting from LPS-activated microglia by regulating cleaved caspase-3 and poly ADP ribose polymerase (PARP) cleavage in N2a cells. In conclusion, our data indicated that balanophonin may delay the progression of neuronal cell death by inhibiting microglial activation.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.345-352
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• 2017

Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-$1{\beta}$ without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the $NF-{\kappa}B$ transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the $NF-{\kappa}B$ pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPS-stimulated RAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the $NF-{\kappa}B$ and AP-1 pathways, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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• pp.325-331
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• 2000

Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ plays important roles in inflammatory responses. Some of tetrahydroisoquinoline (THI) compounds exhibited to inhibit iNOS expression in animal studies and RAW 264.7 cells, but the action of THI on inflammatory reaction was not fully investigated. In the present study, we examined a limited series of THIs (higenamine, YS-51 and THI-52) on the $TNF-{\alpha}$ mRNA expression in mouse peritoneal macrophages by Northern analysis. When thioglycollate-stimulated peritoneal macrophages were incubated with LPS (100 ng/ml), expression of $TNF-{\alpha}$ mRNA was evident and reached its maximum at 2.5 h, which was reduced concentration-dependently by treatment with THIs. When the $TNF-{\alpha}$ activity of macrophage-conditioned media was measured using a TNF-sensitive L929 fibroblast cell line, CCL 1, all THIs increased the cell viability in a concentration dependent manner. The concentrations of THIs used are not cytotoxic by itself when analysed by MTT. Furthermore, nitrite/nitrate level was significantly reduced by the presence of THIs in cells treated with $LPS+interferon-{\gamma}\;(IFN-{\gamma}).$ It is concluded, thus, that these results strongly indicated that THIs can suppress the $TNF-{\alpha}$ expression and reduce NO, which may be useful for the inflammatory disorders.

• 대한본초학회지
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• 제31권1호
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• pp.25-31
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• 2016

Objectives : The present study was conducted to evaluate protective effects of Combined Extract of young persimmon fruit and citrus peel (PCM) in Reflux Esophagitis(RE) rats.Methods : Twenty-four Sprague-Dawley (SD) rats were divided four groups and each group had six rats ; Normal group, RE control group, RE group treated PCM 50 ,100 mg/kg body weight group. Reflux esophagitis was induced that tied the pylorus and fundus in SD rats stomach. PCM was administered at 50, 100 mg/kg body weight 2 hrs prior to induction of RE. After 6 hrs, the effects of PCM treated rats were compared with those of normal and control rats. We have performed an analysis such as pH of stomach secretion, oxidative stress biomarkers in serum, and western blot.Results : The increased esophageal mucosa damage by RE was markedly improved by PCM treatment in a dose-dependent manner. Also, the administration of PCM decreased the elevated serum reactive oxygen species (ROS) and peroxynitrite (ONOO^-) in serum. The protein expressions of anti oxidant such as SOD, catalase, GPx exhibited down-regulation by PCM treatment in tissues. And, PCM effectively reduce inflammatory cytokines such as inflammation-related proteins cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in RE rats. In addition, NFκB and p-IκBɑ were decreased in PCM-adiministrated RE rats. But there was no difference on stomach secretion pH between reflux esophagitis rats and PCM administration rat group.Conclusions : In conclusion, administration of PCM (50, 100 mg/kg body weight) made esophagus have less inflammation and injury by decreased NFκB path way. These findings suggest that PCM could have Improving effects on reflux esophagitis.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.184-190
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• 2016

Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin $E_2(PGE_2)$, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and interleukin $1{\beta}$ (IL-$1{\beta}$), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-${\kappa}B$) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.

• Fisheries and Aquatic Sciences
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• 제21권6호
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• pp.15.1-15.9
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• 2018

Background: Inflammation has been known to associate with many human diseases. The objective of this study was to evaluate an anti-inflammatory effect of ozonated krill (Euphausia superba) oil, which was prepared by the treatment of krill oil using ozone gas. The anti-inflammatory activity was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Results: Ozonated krill oil significantly inhibited nitric oxide (NO) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Ozonated krill oil also reduced the mRNA expression of inflammatory cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ in LPS-stimulated RAW 264.7 macrophages. To elucidate the mechanism underlying the anti-inflammatory activity of ozonated krill oil, we evaluated the effects of ozonated krill oil on the activation of mitogen-activated protein kinases (MAPKs) pathway. Ozonated krill oil suppressed the LPS-stimulated phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK). Conclusion: This study revealed that the ozonated krill oil exhibited an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages. To the best of our knowledge, this is the first report that ozonated krill oil suppressed pro-inflammatory mediator and cytokine expression in LPS-stimulated RAW 264.7 macrophages by inhibiting the phosphorylation of p38 MAPK and JNK.

• 생약학회지
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• 제46권1호
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• pp.12-16
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• 2015

Myrrh is a resinous substance obtained from Commiphora trees, which has long been used as an antiseptic agent. A sesquiterpene, $1{\beta}$, $6{\alpha}$-dihydroxyeudesm-4(15)-ene (DE), was isolated from the hot water extract of Myrrh. In the present study, we found that DE attenuates the lipopolysaccharide (LPS)-induced inflammation in BV2 microglial cells. DE significantly inhibited LPS-induced production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in BV2 microglia in a concentration-dependent manner without cytotoxic effect. Furthermore, DE dose-dependently suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results suggest that DE may be a good candidate to regulate LPS-induced inflammatory response.

• 생약학회지
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• 제51권3호
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• pp.163-170
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• 2020

Mahaenggamsuk-tang (MHGS) has been widely used in Korea and China for the treatment of various diseases. MHGS was constituted the Ephedrea Herba, Armenicae Semen, Glycyrrhizae Radix and Gypsum Fibrosum. In this study, we have made three different solvents extract as MHGS water extract (MHGS-W), MHGS 50% EtOH extract (MHGS-50E), and MHGS 100% EtOH extract (MHGS-100E). The MHGS-W, MHGS-50E and MHGS-100E showed the discernible difference patterns on HPLC analysis. Furthermore, MHGS-50E and MHGS-100E significantly increased the DPPH and ABTS radical scavenging effects than MHGS-W. In addition, the MHGS-50E and MHGS-100E also inhibited significantly nitric oxide (NO) and prostaglandin E2 (PGE₂) production, and inducible nitric oxide synthase (iNOS) cyclooxygenase-2 (COX-2) protein expression in RAW264.7. On the other hand, MHGS-50E and MHGS-W showed remarkable protection on the HT22 cell via heme oxygenase (HO)-1, but MHGS-100E did not show. The results of this study proved that MHGS-50E has greater potential therapeutic uses by exerting antioxidant, anti-inflammatory and neuroprotective effects compared to MHGS-100E, MHGS-W. Our study suggests that the different solvent might be affected the biological activities when make the traditional herbal medicines including MHGS.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1079-1086
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• 2003

The aim of this study was to investigate the effect of trauma on cytochrome P450 (CYP) gene expression and to determine the role of Kupffer cells in trauma-induced alteration of CYP isozymes. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride ($GdCl_3$) was intravenously injected at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h of FFx, liver tissues were isolated to determine the mRNA and protein expression of CYP isozymes and NADPH-P450 reductase by reverse transcription-polymerase chain reaction and Western immunoblotting, respectively. In addition, the mRNA levels of tumor necrosis factor alpha (TNF-$\alpha$), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were evaluated. FFx increased the mRNA level of CYP1A1; an increase that was not prevented by $GdCl_3$. There were no significant differences in the mRNA expression of CYP1A2, 2B1 and 2E1 among any of the experimental groups. The protein levels of CYP2B1 and 2E1 were significantly decreased by FFx; a decrease that was not prevented by $GdCl_3$ treatment. The gene expression of NADPH-P450 reductase was unchanged by FFx. FFx significantly increased the expression of TNF-$\alpha$ mRNA; an increase that was attenuated by $GdCl_3$. The mRNA expression of HO-1 was increased by FFx, but not by $GdCl_3$ . Our findings suggest that FFx differentially regulates the expression of CYP isozyme through Kupffer cell-independent mechanisms.