• International Journal of Oral Biology
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• 제45권2호
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• pp.42-50
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• 2020

Lysophosphatidic acid (LPA) is a lipid messenger mediated by G protein-coupled receptors (LPAR1-6). It is involved in the pathogenesis of certain chronic inflammatory and autoimmune diseases. In addition, it controls the self-renewal and differentiation of stem cells. Recent research has demonstrated the close relationship between periodontitis and various diseases in the human body. However, the precise role of LPA in the development of periodontitis has not been studied. We identified that LPAR1 was highly expressed in human periodontal ligament stem cells (PDLSCs). In periodontitis-mimicking conditions with Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS) treatment, PDLSCs exhibited a considerable reduction in the cellular viability and osteogenic differentiation potential, in addition to an increase in the inflammatory responses including tumor necrosis factor-α and interleukin-1β expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Of the various LPAR antagonists, pre-treatment with AM095, an LPAR1 inhibitor, showed a positive effect on the restoration of cellular viability and osteogenic differentiation, accompanied by a decrease in NF-κB signaling, and action against Pg-LPS. These findings suggest that the modulation of LPAR1 activity will assist in checking the progression of periodontitis and in its treatment.

• 한국식품영양학회지
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• 제31권4호
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• pp.495-501
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• 2018

Ultraviolet B (UVB) exposure is a risk factor for skin damage resulting in oxidative stress, inflammation, and cell death. The purpose of this study was to investigate the physicochemical properties of Platycodon grandiflorum (PG) to improve its biological activities using a three-step steaming process. We investigated the protective effects of PG and steamed PG extracts on human dermal fibroblasts (HDFs) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the PG extracts was evaluated by measuring the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging activity. ABTS and DPPH were shown by the 0, 30, and 70% ethanol extracts of 2S-PG and 3S-PG ($IC_{50}$, 28~45 and $27{\sim}30{\mu}g/mL$, respectively). Treatment of UVB-irradiated cells with steamed PG ($25{\sim}400{\mu}g/mL$) did not affect their viability. The streamed PG extract suppressed UVB-induced generation of reactive oxygen species (ROS). In addition, streamed PG extract reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated HDF, regulating nuclear factor $(NF)-{\kappa}B$ expression. These findings suggest that steamed PG extract may be potentially effective against inflammation associated with UVB-induced oxidation stress.

• 한방비만학회지
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• 제20권1호
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• pp.10-19
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• 2020

Objectives: Oxidative stress-mediated neuroinflammation has been supposed as a crucial factor that contributes to the pathogenesis of many neurodegenerative diseases. In this study, we aimed to investigate the protective activity against oxidative stress and neuroinflammation of protocatechuic acid (PA), active phenolic compound from Momordica Charantia. Methods: Protective activity of PA from oxidative stress was performed under in vitro conditions. Our study investigated the protective mechanism of PA from neuroinflammation in cellular system using C6 glial cell. To investigate the improvement the effects on oxidative stress and neuroinflammation, we induced oxidative stress by H₂O₂ (100 μM) stimulation and induced neuroinflammation by treatment with lipopolysaccharide (LPS) (1 ㎍/mL) and interferon-gamma (IFN-γ) (10 ng/mL) in C6 glial cells. Results: PA showed strong radical scavenging effect against 1,1-dipenyl-2-picrylhydrazyl, hydroxy radical (·OH) and nitric oxide (NO). Under oxidative stress treated by H₂O₂, the result showed the increased mRNA expressions of oxidative stress markers such as nuclear factor-kappaB (NF-κB), cyclooxygenase (COX-2) and inducible nitric oxide (iNOS). However, the treatment of PA led to reduced mRNA expressions of NF-κB, COX-2 and iNOS. Moreover, PA attenuated the production of interleukin-6 and scavenged NO generated by both endotoxin LPS and IFN-γ together. Furthermore, it also reduced LPS and IFN-γ-induced mRNA expressions of iNOS and COX-2. Conclusions: In conclusion, our results collectively suggest that PA, phenolic compound of Momordica Charantia, could be a safe anti-oxidant and a promising anti-neuroinflammatory molecule for neurodegenerative diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.403-412
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• 2020

Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

• 대한한방부인과학회지
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• 제34권1호
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• pp.34-47
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• 2021

Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.

• BMB Reports
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• 제54권11호
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• pp.557-562
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• 2021

Microglial activation is closely associated with neuroinflammatory pathologies. The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasomes are highly organized intracellular sensors of neuronal alarm signaling. NLRP3 inflammasomes activate nuclear factor kappa-B (NF-κB) and reactive oxygen species (ROS), which induce inflammatory responses. Moreover, NLRP3 dysfunction is a common feature of chronic inflammatory diseases. The present study investigated the effect of a novel thiazol derivative, N-cyclooctyl-5-methylthiazol-2-amine hydrobromide (KHG26700), on inflammatory responses in lipopolysaccharide (LPS)-treated BV-2 microglial cells. KHG26700 significantly attenuated the expression of several pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, in these cells, as well as the LPS-induced increases in NLRP3, NF-κB, and phospho-IkBα levels. KHG26700 also suppressed the LPS-induced increases in protein levels of autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 (LC3), and beclin-1, as well as downregulating the LPS-enhanced levels of ROS, lipid peroxidation, and nitric oxide. These results suggest that the anti-inflammatory effects of KHG26700 may be due, at least in part, to the regulation of the NLRP3-mediated signaling pathway during microglial activation.

• 대한임상검사과학회지
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• 제54권3호
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• pp.201-208
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• 2022

Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

• Nutrition Research and Practice
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• 제11권5호
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• pp.365-372
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• 2017

BACKGROUND/OBJECTIVES: Owing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik, was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies. MATERIALS/METHODS: Ginseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis. RESULTS: The plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group (P < 0.05). In addition, nuclear factor-kappaB (NF-${\kappa}B$) expression in the GBRD group was significantly lower than that in the RCD group. CONCLUSIONS: GBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti-inflammatory status in HFD-fed mice via CAT and GPx upregulation and NF-${\kappa}B$ downregulation. These effects were significantly higher than those of RCD.

• BMB Reports
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• 제44권7호
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• pp.484-489
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• 2011

Annexin-1 (ANX1) is an anti-inflammatory protein as well as an important modulator in inflammation. However, the precise action of ANX1 remains unclear. To elucidate the protective effects of ANX1 on lipopolysaccharide (LPS)-induced murine macrophage Raw 264.7 cells, we constructed a cell-permeable Tat-ANX1 protein. The transduced Tat-ANX1 protein markedly inhibited the expression of cyclooxygenase-2, production of prostaglandin $E_2$, and generation of pro-inflammatory cytokines in the cells. Furthermore, transduced Tat-ANX1 protein caused a significant reduction in the activation of nuclear factor-kappa B (NF-${\kappa}B$) and mitogen-activated protein kinase (MAPK). The results indicate that Tat-ANX1 inhibits the production of inflammatory response cytokines and enzymes by blocking NF-${\kappa}B$ and MAPK. Therefore, Tat-ANX1 protein may be useful as a therapeutic agent against various inflammatory diseases.

• 한국응용과학기술학회지
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• 제30권1호
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• pp.173-182
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• 2013

아토피성 피부염은 만성 재발성 염증성 피부질환으로 피부장벽기능의 이상과 환경유발인자에 대한 피부과민성과 연관되어 있다. 이전의 연구에서는 아토피성피부염에 효과적인 약용식물 추출물을 발굴하기 위하여 노회, 자회지정, 석류, 석곡 추출물들의 세포독성, 항산화, 항염, 항알레르기 효과를 검토하였다. 본 연구에서는 지질다당류로 활성화시킨 대식세포 RAW26.7 에 대한 약용식물 추출물들의 항염작용을 보다 상세하게 검토하여 항염작용의 근본적인 분자기전을 확인하고자 하였다. 역전사중합효소연쇄반응분석(reverse transcription polymerase chain reaction analysis) 결과, 석류, 석곡, 노회는 염증성 사이토카인인 IL-6 와 IL-$1{\beta}$ 유전자발현을 현저하게 억제시켰으며 자화지정은 영향이 없었다. 형질주입과 발광효소분석(transfection and luciferase analysis) 결과, 약용식물 모두가 전사 핵인자 카파비(NF-${\kappa}B$)의 활성화를 억제시켰다. 웨스턴 블럿 분석(western blot analysis) 결과, 노회는 JNK MAP 인산화효소의 활성화를 차단하였지만 p38 MAP 인산화효소의 활성화는 차단하지 못하였다. 반면에 자화지정, 석류, 석곡은 JNK MAP 인산화효소뿐만 아니라 p38 MAP 인산화효소의 활성화도 차단하였다. 이들 실험결과들은 노회, 자화지정, 석류, 석곡은 항염효능을 가지고 있으며 따라서 아토피성 피부염의 증상을 경감 또는 완화시키는 잠재력이 있음을 보여 준다.