• Biomolecules & Therapeutics
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• 제20권5호
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• pp.463-469
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• 2012

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.70-78
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• 2009

Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

• 동의생리병리학회지
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• 제22권2호
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• pp.415-421
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• 2008

Pro-inflammatory mediators, such as prostaglandin $E_2$ (PGE2), nitric oxide (NO), and cyclooxygenases-2 (COX-2), play pivotal roles in normal as well as transformed cells. Previous studies have shown that Euphorbiae humifusae Wind exhibits anti-proliferative and antioxidant activities. However, the it's anti-inflammatory properties are unclear. In this study, we examine the effects of water extract of E. humifusae (WEEH) on the expression of COX-2 and the production of $PGE_2$ in human lymphatic U937 cells. Treatment of phorbol 12-myristate-13-acetate (PMA) significantly induced COX-2 expression and $PGE_2$ production in U937 cells. However, pretreatment WEEH markedly inhibited the PMA-induced COX-2 expression and $PGE_2$ production in a dose-dependent manner. Moreover, WEEH prevented the elevated early growth response gene-1 (Egr-1) expression and nuclear factor-kappaB ($NF{-\kappa}B\; p65$) nuclear translocation stimulated by PMA treatment. Taken together, the present data indicate that WEEH exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the $NF{-\kappa}B$ and Egr-1 signaling pathway.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.146-156
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• 2018

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.

• 대한화장품학회지
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• 제43권2호
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• pp.103-114
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• 2017

떡쑥(Gnaphalium affine D. Don, GA)은 동아시아 지역에서 식용으로 사용되고 있으며, 예로부터 전통적인 민간요법 약재로 사용되어 왔다. 현재 떡쑥 추출물(GA extract, GAE)의 항산화 활성과 항보체 활성 등은 알려져 있으나, 항염과 항알러지 효능 및 그 작용 기작은 자세히 알려져 있지 않다. 본 연구에서는 염증 매개인자인 산화질소, 프로스타글란딘 $E_2$, Toll-유사수용체 4, 에오탁신-1, 히스타민의 활성화에 대한 GAE의 저해효과를 평가하였다. 본 연구를 통해, GAE는 유도성 산화질소 합성효소와 COX-2의 발현을 저해함을 확인하였으며, 이를 통해 산화질소와 프로스타글란딘 $E_2$의 생성을 저해함을 확인하였다. GAE는 LPS로부터 유도된 Toll-유사수용체 4의 발현에도 영향을 미치는 것을 확인하였으며, A23187로부터 유도되는 비만세포의 히스타민 방출의 억제에도 효과적으로 작용하는 것을 확인하였다. 또한 IL-4로부터 유도된 에오탁신-1의 생성도 효과적으로 억제하는 결과를 확인하였다. 이상의 결과로부터 GAE는 항염증과 항알러지 효능을 가진다고 사료되며, 향후 항염증 및 항알러지 화장품 원료로서의 이용가능성을 보였다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제21권4호
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• pp.332-344
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• 1999

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. Interleukin-6 (IL-6) is involved in the final differentiation of B cells into antibody-producing cells. Interleukin-8 (IL-8) is a neutrophil chemotactic factor that plays an important role in the recruitment of neutrophil to inflammatory loci. Inflammatory mediators by cells in the gingiva have been implicated in the initiation and progression of periodontitis and oral infection. The purpose of this study was conducted to investigate the effect of lipopolysaccharide (LPS), staphylococcus enterotoxin B (SEB) on production of IL-6 and IL-8 by human gingival and facial dermal fibroblasts. Primary cultured human gingival and facial dermal fibroblasts were incubated with LPS (0.01, 0.1, $1.0{\mu}g/ml$), SEB (0.01, 0.1, $1.0{\mu}g/ml$) or LPS $(0.1{\mu}g/ml)$ plus SEB $(0.1{\mu}g/ml)$. Culture supernatants were collected at 24, 48, and 72 hrs and assessed for IL-6 and IL-8 production by enzyme-linked immunosorbent assay. IL-6 production in gingival fibroblasts stimulated with LPS was higher than that with SEB. IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-6 production in facial dermal fibroblasts was increased only by stimulation with a high concentration of LPS $(1.0{\mu}g/ml)$. Its production in facial dermal fibroblasts by exposure with SEB was decreased in comparison with control, nontreated cells. Therefore, gingival fibroblasts showed higher sensitivity than facial dermal fibroblasts in response to low concentration of LPS. Also, IL-6 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in gingival fibroblasts was enhanced greatly only by stimulation of high concentration of LPS $(1.0{\mu}g/ml)$. That by exposure with SEB was increased only in 24 hrs cultivation. IL-8 production by double exposure with LPS plus SEB was amplified in comparison with single exposure of LPS or SEB. IL-8 production in facial dermal fibroblasts was decreased by LPS and increased only in 48 hrs cultivation by SEB. IL-8 production by double exposure with LPS plus SEB was enhanced only in 48 hrs cultivation in comparison with single exposure of LPS or SEB. therefore, IL-6 and IL-8 production were released at various quantities according to bacterial toxin applied and site of fibroblast harvested. These results suggest that gingival fibroblasts may be concerned with IL-6 and IL-8 related inflammatory response more than facial dermal fibroblasts.

• 한방재활의학과학회지
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• 제26권3호
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• pp.31-49
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• 2016

Objectives The study was designed to evaluate the healing effects of Joaguihwan (JGH) extract on Anti-oxidation, Anti-inflammatory in RAW 264.7 Cells and factors related with bone metabolism in skull fractured Rat. Methods The fracture healing effect of JGH was measured by scavenging activities of1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and nitric oxide (NO) in RAW 264.7 cells. The inhibitory effect against the production of inflammatory mediators including interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necosis factors-${\alpha}$ (TNF-${\alpha}$) expression was inhibited in RAW 264.7 cells was experimented using JGH. The effects of JGH on healing fractured rats was measured by osteocalcin, calcitonin, CTXII, TGF-${\beta}$, BMP-2, Insulin, ALP in the serum. and was checked every 3 weeks from 0 week to 6week using x-ray. Results 1. DPPH free radica and ABTS scavenging activity of JGH were increased according to concentration of JGH in RAW 264.7 Cells. 2. In the experiment, NO, IL-$1{\beta}$, IL-6, TNF-${\alpha}$ all showed decrease, in general. Especially NO and IL-$1{\beta}$ showed significantly decrease at a concentration of 10, 100 (${\mu}g/ml$). 3. In the production of osteocalcin in the serum, JGH 200, 400 mg/kg experimental group showed significant increased effect at 2 weeks. 4. In the production of calcitonin in the serum. JGH 200 mg/kg experimental group showed significant increased effect at 4, 6 weeks. JGH 400 mg/kg experimental group showed significant increased effect at 2, 4, 6 weeks. 5. In the production of CTX, TGF-${\beta}$, BMP-2 in the serum, experimental group showed increased effect. but no significant effect. 6. In the production of insulin in the serum. JGH 200, 400 mg/kg experimental group showed significant decrease effect at 2, 4, 6 weeks. 7. In the production of ALP in the serum. JGH 200 mg/kg experimental group showed significant increased effect at 2, 4, 6 weeks. JGH 400 mg/kg experimental group showed significant increased effect at 4, 6 weeks. 8. In the change of X-ray, the experimental group showed better healing effects on skull fractured rats than control group. Conclusions From above results, JGH showed healing effect on Anti-oxidation, Anti-inflammatory in RAW 264.7 Cells, factors related with bone metabolism in the serum of skull fractured rat and x-ray, which is expected to be applied in clinics.

• 한국유기농업학회지
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• 제22권3호
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• pp.469-481
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• 2014

본 연구진은 신규 미생물인 Nocardia sp. CS682 균주에서 항균물질인 nargenicin을 확보하고, 그 유도체 5종을 확보하여 그람양성, 음성 및 다약제 내성균에 대한 항균 효능 및 LPS로 자극된 대식세포에서의 nitric oxide 생성 억제능을 확인하였다. Nargenicin 유도체들은 nargenicin 및 vancomycin에 비교하여 우수한 항균 활성을 보여주었으며, compound 4 및 5는 광범위한 항균 효능 외에 nitric oxide 생성 억제능을 보여 항균-항염효과를 가지는 dual effector로써 감염, 면역 질환에 응용 가능성을 시사하였다. Nargenicin 유도체들은 향후 염증반응에서의 면역 조절 기작에 대한 추가 연구가 필요할 것으로 사료된다.

• 한국해양바이오학회지
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• 제13권2호
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• pp.86-93
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• 2021

A high salt diet contributes to kidney damage by causing hypoxia and oxidative stress. Recently, an increase in dietary salt has been reported to induce an inflammatory phenotype in immune cells, further contributing to kidney damage. However, studies on the exact mechanism and role of a high salt diet on the inflammatory response in the kidneys are still insufficient. In this study, a cisplatin-induced acute kidney injury model using C57BL/6 mice was used to analyze the effect of salt intake on kidney injury. Results showed that high salt administration aggravated kidney edema in mice induced by treatment with cisplatin. Moreover, the indicators of kidney and liver function impairment were significantly increased in the group cotreated with high salt compared with that treated with cisplatin alone. Furthermore, the exacerbation of kidney damage by high salt administration was also associated with a decrease in the number of cells in the immune regulatory system. Additionally, high salt administration further decreased renal perfusion functions along with increased cisplatin-induced damage to proximal tubules. This was accompanied by increased expression of T cell immunoglobulin, mucin domain 1 (a biomarker of kidney injury), and Bax (a pro-apoptotic factor). Moreover, cisplatin-induced expression of proinflammatory mediators and cytokines, including cyclooxygenase-2 and tumor necrosis factor-α in kidney tissue, was further increased by high salt intake. Therefore, these results indicate that the kidney's inflammatory response by high salt treatment can further promote kidney damage caused by various pathological factors.

• Journal of Ginseng Research
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• 제46권5호
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• pp.628-635
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• 2022

Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4⁺ T-helper cells, CD19⁺ B-cells, and CD4⁺ and CD25⁺ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.