• Journal of Ginseng Research
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• v.39 no.4
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• pp.365-370
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• 2015

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to $200{\mu}M$) for 1 h before treatment with 1 mg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

• ALGAE
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• v.29 no.2
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• pp.165-174
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• 2014

Ecklonia cava is a common edible brown algae that is plentiful in Jeju Island of Republic of Korea. Polyphenols from E. cava have strong anti-inflammatory activity. However, a large number of the by-products from E. cava processing are discarded. In the present study, to utilize these by-products, we assessed the anti-inflammatory activity of the polyphenol-rich fraction (PRF) from E. cava processing by-product (EPB) in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. Four compounds, namely eckol, eckstolonol, dieckol, and phlorofucofuroeckol-A, were isolated and identified from PRF. We found that PRF suppressed the production of nitric oxide (NO), inducible nitric oxide synthase, and cyclooxygenase-2 in the LPS-induced cells. Furthermore, the protective effect of PRF was investigated in vivo in LPS-stimulated inflammation zebrafish model. PRF had a protective effect against LPS-stimulated toxicity in zebrafish embryos. In addition, PRF inhibited LPS-stimulated reactive oxygen species and NO generation. According to the results, PRF isolated from EPB could be used as a beneficial anti-inflammatory agent, instead of discard.

• Clinical and Experimental Pediatrics
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• v.64 no.1
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• pp.37-43
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• 2021

Background: Animal studies have shown that a leukocyte influx precedes the development of bronchopulmonary dysplasia (BPD) in premature sheep. The CXC chemokine receptor 2 (CXCR2) pathway has been implicated in the pathogenesis of BPD because of the predominance of CXCR2 ligands in tracheal aspirates of preterm infants who later developed BPD. Purpose: To test the effect of CXCR2 antagonist on postnatal systemic and pulmonary inflammation and alveolarization in a newborn Sprague-Dawley rat model of BPD. Methods: Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into the newborn rats on postnatal day 1 (P1), P3, and P5 to induce systemic inflammation and inhibit alveolarization. In the same time with LPS administration, CXCR2 antagonist (SB-265610) or vehicle was injected i.p. to investigate whether CXCR2 antagonist can alleviate the detrimental effect of LPS on alveolarization by attenuating inflammation. On P7 and P14, bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) were collected from the pups. To assess alveolarization, mean cord length and alveolar surface area were measured on 4 random nonoverlapping fields per animal in 2 distal lung sections at ×100 magnification. Results: Early postnatal LPS administration significantly increased neutrophil counts in BALF and PB and inhibited alveolarization, which was indicated by a greater mean cord length and lesser alveolar surface area. CXCR2 antagonist significantly attenuated the increase of neutrophil counts in BALF and PB and restored alveolarization as indicated by a decreased mean cord length and increased alveolar surface area in rat pups exposed to early postnatal systemic LPS. Conclusion: CXCR2 antagonist preserved alveolarization by alleviating pulmonary and systemic inflammation induced by early postnatal systemic LPS administration. These results suggest that CXCR2 antagonist can be considered a potential therapeutic agent for BPD that results from disrupted alveolarization induced by inflammation.

• The Korean Journal of Food And Nutrition
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• v.32 no.2
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• pp.106-113
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• 2019

The objective of this study was to evaluate the effect of fermented Kalopanax pictus (KP-F) on macrophage activation and its effect as a competitive inhibitor of LPS and inhibitory effect on endotoxemia. The results showed that KP-F could activate macrophage in a dose-dependent manner, and KP-F was confirmed to act as a ligand for TLR4. Also, it was found that KP-F did not exhibit the same biotoxicity as LPS in intraperitoneal injection, and that it could suppress the neutrophil migration induced by LPS administration. In normal mice, the body weight, tissue weight, and amount of nitrite and pro-inflammatory cytokines in serum showed no significant changes with KP-F diet for 2 weeks, confirming that administration of KP-F in normal mice did not lead to over activation of immune response and biotoxicity. In the mouse model of endotoxemia induced by LPS and D-galactosamine(D-GalN) in sub-lethal dose, the diet of KP-F effectively inhibited the amount of nitrite and cytokines in the blood, and thus was found to be able to relieve the hepatic and kidney injury. In addition, in the endotoxemia mouse model induced by LPS and D-GalN of lethal dose, the survival rate was increased by KP-F diet in a dose-dependent manner.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.40-50
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• 2018

Objectives: The aim of this study is to investigate anti-inflammatory effects of Kyungheechunggan-tang (KHCGT) on LPS- induced RAW 264.7 cells and LX-2 cells and anti-fibrotic effects of KHCGT on LX-2 cells. Materials and Methods: Three types of KHCGTs (KHCGT-A, -B, and -C) by narrowing down the number of constituent herbs from 9 (KHCGT-A) to 5 (KHCGT-B) and to 3 (KHCGT-C) were developed. To understand pharmacological effects of KHCGT, three types of KHCGTs were treated on RAW 264.7 cells and LX-2 cells. Anti-inflammatory activities of KHCGT were evaluated by ELISA assay for pro-inflammatory cytokines, IL-6, $TNF-{\alpha}$ and IL-10, in LPS-stimulated RAW 264.7 cells and for IL-6 production in LPS-induced LX-2 cells. In addition, anti-fibrotic effects of KHCGT were determined by quantitative real-time PCR assay for fibrosis-related genes, ${\alpha}-SMA$, collagen1A1, TIMP1, MMP-2, in LX-2 cells. Results: KHCGT-A and KHCGT-C showed inhibitory effects on secretion of IL-6 in LPS-stimulated RAW 264.7 cells and LX-2 cells. KHCGT-B and KHCGT-C exhibited inhibitory effects on the expression of pro-inflammatory cytokines such as IL-6, $TNF-{\alpha}$, and IL-10 in LPS-stimulated RAW 264.7 cells. The mRNA expression levels of collagen1A1 and MMP-2 were significantly reduced by KHCGT-C whereas TIMP-1 was suppressed by KHCGT-A and KHCGT-B in LX-2 cells. Among three different formulas, KHCGT-C demonstrated the most remarkable effects on inflammation and fibrosis. Conclusions: In this study, KHCGT showed both anti-inflammatory and anti-fibrotic effects which make it to be a prospective agent for chronic liver diseases with inflammation and fibrosis.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.185-190
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• 2019

Periodontitis is a chronic inflammatory disease and gums pull away from the teeth and form spaces. The main goal of treatment is to control the infection and anti-inflammation. Eucommia ulmoides Oliv. Bark (EU) is a traditional Korean herbal used for the treatment of arthritis and hypertension. In the present study, we investigated the anti-inflammatory properties of EU in Porphyromonas gingivalis-LPS (LPS-PG) induced YD-38 epithelial cells. We observed significant inhibition of nitric oxide (NO) production and the expression of interleukin-8 (IL-8), interleukin-6 (IL-6), tumor necrosis factor alpha ($TNF-{\alpha}$), cyclooxygenase-2 (COX-2) in LPS-PG-induced YD-38 cells. These results support that EU has an anti-inflammatory effects for the treatment of periodontitis.

• Korean Journal of Acupuncture
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• v.36 no.3
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• pp.162-170
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• 2019

Objectives : Increasing evidence suggests that parasympathetic vagus nerve activity plays a role in modulating acupuncture-induced anti-inflammatory reaction, but the function of sympathetic nerve is not known. Here, we investigated whether splanchnic sympathetic nerve activity was involved in the regulation of splenic expression of $TNF-{\alpha}$ mRNA by electroacupuncture (EA) in LPS-injected animals. Methods : DiI was injected into the stomach or celiac ganglion (CG) for retrograde labeling of the target tissues. EA was given at ST36 and the electrical stimulation on the sciatic nerve in LPS-injected mice. c-Fos signals in the tissues were analyzed by immunofluorescence staining, and $TNF-{\alpha}$ mRNA was analyzed by real-time PCR. Results : Application of EA at ST36 or electrical stimulation on the sciatic nerve induced c-Fos expression in neurons of the spinal cord and celiac ganglion (CG). Then, the vagotomy reduced c-Fos levels in CG neurons but not in the spinal cord in animals given EA. Expression of $TNF-{\alpha}$ mRNA which was induced in the spleen after LPS was significantly inhibited by EA, then the vagotomy elevated $TNF-{\alpha}$ mRNA level similar to that in LPS-injected animals. Splanchnectomy in animals given LPS and EA also increased $TNF-{\alpha}$ mRNA though it was less effective than vagotomy. Conclusions : Our data suggest that EA delivered to the spleen via the splanchnic sympathetic nerve may be involved in attenuating splenic inflammatory responses in LPS-injected animals.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.395-401
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• 2021

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

• Journal of Periodontal and Implant Science
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• v.52 no.1
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• pp.28-38
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• 2022

Purpose: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. Methods: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. Results: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. Conclusions: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

• Journal of Life Science
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• v.33 no.1
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• pp.50-55
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• 2023

This study was designed to determine the activities of Rosa davurica Pall. leaf extract and their regulatory mechanisms in macrophage inflammation. Anti-inflammatory potential of Rosa davurica Pall. leaf extract was evaluated by measuring the nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) synthesis in lipopolysaccharide (LPS)-treated macrophage Raw 264.7 cells. Rosa davurica Pall. leaf extract potently inhibited LPS-induced NO release in a dose dependent manner. However, cell viability decreased to about 50% at high dose of 500 ㎍/ml, resulting in cytotoxicity. LPS-induced iNOS protein expression was also reduced significantly after treatment with Rosa davurica Pall. leaf extract. Furthermore, extract of Rosa davurica Pall. attenuated LPS-mediated phosphorylation of IκB and nuclear factor (NF-κB). Suppression of NF-κB signaling by treatment with PDTC, an NF-κB specific inhibitor, accelerated the inhibition of NO production and iNOS protein expression. These results suggest that Rosa davurica Pall. exhibits the anti-inflammatory potential in LPS-induced macrophage inflammation, partly through inhibition of NO production by down-regulation of NF-κB signaling.