• Journal of Acupuncture Research
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• 제34권2호
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• pp.1-18
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• 2017

Objectives : The purpose of this study was to evaluate the effects of water extracts of Eucommiae cortex (EC), Psoraleae semen (PS), and their combination on receptor activator of nuclear factor-kappa-B ligand (RANKL)-induced osteoclast differentiation. Methods : We assayed the protein expression levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, mitogen-activated protein kinases (MAPKs), and ${\beta}-actin$ in cell lysates using western blotting. Similarly, mRNA expression levels of NFATc1, c-Fos, tartrateresistant acid phosphate (TRAP), and glyceraldehyde-3-phosphate dehydrogenase, spermatogeni (GAPDHS) from bone marrow macrophages (BMMs) were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, we determined the anti-osteoporotic effects of the water extracts of EC, PS, and their combination in a lipopolysaccharide (LPS)-induced bone-loss mouse model. Results : The in vitro data revealed showed that the combination of EC and PS extract showed a more remarkable inhibition of osteoclast differentiation than each herb did alone. The combination downregulated the induction of c-Fos, NFATc1, and TRAP by suppressing the phosphorylation of p38 and c-Jun N-terminal kinases (JNKs) and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). Lastly, the in vivo data showed that PS reduced the LPS-induced bone erosion. Conclusion : The result of this study suggests that EC and PS could be potential therapeutic agents for bone loss diseases such as osteoporosis.

• Animal Bioscience
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• 제36권2호
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• pp.315-321
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• 2023

Objective: The study was conducted to investigate the dephosphorylation of Pseudomonas aeruginosa flagellin (PA FLA) by sweet potato purple acid phosphatase (PAP) and the effect of the enzyme on the flagellin-mediated inflammatory response in the A549 lung epithelial cell line. Methods: The activity of sweet potato PAP on PA FLA was assayed at different pH (4, 5.5, 7, and 7.5) and temperature (25℃, 37℃, and 55℃) conditions. The release of interleukin-8 (IL-8) and the activation of nuclear factor kappa- light-chain-enhancer of activated B cells (NF-κB) in A549 cells exposed to PA FLA treated with or without sweet potato PAP was measured using IL-8 and NF-κB ELISA kits, respectively. The activation of toll-like receptor 5 (TLR5) in TLR5-overexpressing HEK-293 cells exposed to PA FLA treated with or without sweet potato PAP was determined by the secreted alkaline phosphatase-based assay. Results: The dephosphorylation of PA FLA by sweet potato PAP was favorable at pH 4 and 5.5 and highest at 55℃. PA-FLA treated with the enzyme decreased IL-8 release from A549 cells to about 3.5-fold compared to intact PA FLA at 1,000 ng/mL of substrate. Moreover, PA-FLA dephosphorylated by the enzyme repressed the activation of NF-κB in the cells compared to intact PA FLA. The activation of TLR5 by PA-FLA was highest in TLR-overexpressing HEK293 cells at a substrate concentration of 5,000 ng/mL, whereas PA FLA treated with the enzyme strongly repressed the activation of TLR5. Conclusion: Sweet potato PAP has the potential to be a new alternative agent against the increased antibiotic resistance of P. aeruginosa and may be a new conceptual feed additive to control unwanted inflammatory responses caused by bacterial infections in animal husbandry.

• Journal of Periodontal and Implant Science
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• 제52권2호
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• pp.127-140
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• 2022

Purpose: In dental avulsion, delayed replantation usually has an uncertain prognosis. After tooth replantation, complex inflammatory responses promote a return to periodontal tissue homeostasis. Various types of cytokines are produced in the inflammatory microenvironment, and these cytokines determine the periodontal tissue response. This study aimed to identify the gene expression profiles of replanted teeth and evaluate the functional differences between immediate and delayed replantation. Methods: Maxillary molars from Sprague-Dawley rats were extracted, exposed to a dry environment, and then replanted. The animals were divided into 2 groups according to the extra-oral time: immediate replantation (dry for 5 minutes) and delayed replantation (dry for 60 minutes). Either 3 or 7 days after replantation, the animals were sacrificed. Periodontal soft tissues were harvested for mRNA sequencing. Hallmark gene set enrichment analysis was performed to predict the function of gene-gene interactions. The normalized enrichment score (NES) was calculated to determine functional differences. Results: The hallmark gene sets enriched in delayed replantation at 3 days were oxidative phosphorylation (NES=2.82, Q<0.001) and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway (NES=1.52, Q=0.034). At 7 days after delayed replantation, TNF-α signaling via the NF-κB pathway (NES=-1.82, Q=0.002), angiogenesis (NES=-1.66, Q=0.01), and the transforming growth factor-beta signaling pathway (NES=-1.46, Q=0.051) were negatively highlighted. Conclusions: Differentially expressed gene profiles were significantly different between immediate and delayed replantation. TNF-α signaling via the NF-κB pathway was marked during the healing process. However, the enrichment score of this pathway changed in a time-dependent manner between immediate and delayed replantation.

• 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.

• 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.

• Journal of Ginseng Research
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• 제44권6호
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• pp.833-842
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• 2020

Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

• 대한화장품학회지
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• 제44권3호
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• pp.239-247
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• 2018

만성적인 염증은 낭포성 섬유증, 암, 치매, 아토피성 질환, 비만 등과 같은 염증성 질환의 원인이 된다. 또한 염증의 발생단계에 관여하는 일부 신호물질은 피부조직의 손상과 노화에도 영향을 주는 것으로 알려져 있기 때문에 염증발생 매커니즘을 조절하기 위한 연구가 활발하게 이루어지고 있다. 최근에는 염증반응을 억제하거나 예방하기 위해, 몇몇 식물로부터 항염증 소재를 개발하려는 연구들이 이루어지고 있다. 특히 Stevia rebaudiana는 특유의 풍미를 가지는 천연감미료 스테비올배당체(steviol glycoside, SG)를 생성하는데, 일부 SG에 대한 연구를 통해 염증억제 활성이 있는 것으로 알려져 있다. 본 연구에서는 기존연구를 통해 항염증 효능이 있는 것으로 확인된 스테비오사이드, 리버디오사이드 A, 스테비올 이외에도 항염증 소재로 활용될 가능성이 있는 SG가 더 존재할 것으로 예상하였다. 이를 확인하기 위하여 우리는 S. rebaudiana에서 얻은 SG의 nitric oxide(NO) 생성억제활성을 RAW 264.7 세포주를 대상으로 스크리닝 하였다. 그 결과 steviol ${\beta}-glucopyranosyl$ ester (SGE)가 동일한 농도 조건의 SG 중에서 가장 높은 억제활성을 보여주었다. 또한, $interleukin-1{\alpha}$ ($IL-1{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), cyclooxygenase-2 (COX-2), nuclear factor kappa-light chain-enhancer of activated B cells ($NF-{\kappa}B$), inducible nitric oxide synthase (iNOS)와 같은 염증관련 인자의 mRNA 발현량 또한 농도의존적으로 감소시키는 것으로 확인되었다. 이러한 연구결과를 통해 SGE는 마우스 대식세포인 RAW 264.7 세포에서 항염증 활성 및 NO 생성 억제 효과가 있음을 확인하였다. 이를 통하여 SGE가 항염증 소재로 활용될 잠재성이 있음을 확인하였다.

• Journal of Ginseng Research
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• 제41권4호
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• pp.513-523
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• 2017

Background: Korean Red Ginseng extracts (RGE) have been suggested as effective immune modulators, and we reported that ginsenosides possess anti-inflammasome properties. However, the properties of nonsaponin components of RGE have not been well studied. Methods: To assess the roles of nonsaponin fractions (NS) in NLRP3 inflammasome activation, we treated murine macrophages with or without first or second inflammasome activation signals with RGE, NS, or saponin fractions (SF). The first signal was nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$)-mediated transcription of pro-interleukin (IL)-$1{\beta}$ and NLRP3 while the second signal triggered assembly of inflammasome components, leading to IL-$1{\beta}$ maturation. In addition, we examined the role of NS in IL-6 production and IL-$1{\beta}$ maturation in mice. Results: NS induced IL-$1{\beta}$ and NLRP3 transcription via toll-like receptor 4 signaling, whereas SF blocked expression. During the second signal, SF attenuated NLRP3 inflammasome activation while NS did not. Further, NS-injected mice presented increased IL-$1{\beta}$ maturation and IL-6 production. Conclusion: SF and NS of RGE play differential roles in the NLRP3 inflammasome activation. Hence, RGE can be suggested as an NLRP3 inflammasome modulator.

• Toxicological Research
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• 제33권4호
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• pp.325-332
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• 2017

3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is most commonly isolated from red algae. The present study was designed to investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)-stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression of the development of AD symptoms compared with the control treatment (induction-only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph nodes with reduced thickness and length, a decrease in ear edema, and reduced levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine macrophages, BDB (12.5, 25, 50, and $100{\mu}M$) suppressed the production of interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also had an inhibitory effect on the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and signal transducer and activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules involved in cellular inflammation. Taken together, the results show that BDB treatment alleviates inflammatory responses in an atopic dermatitis mouse model and RAW 264.7 macrophages. These results suggest that BDB may be a useful therapeutic strategy for treating conditions involving allergic inflammation such as atopic dermatitis.

• 생명과학회지
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• 제33권2호
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• pp.176-182
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• 2023

석곡의 줄기는 전통 동양의학에서 위를 보하고, 진액을 보충하며, 열을 내리는 것에 사용되어 왔다. 본 연구에서는 RBL-2H3 세포에서 비만세포 탈과립과 TNF-α, IL-4, histidine decarboxylase (HDC) 발현에 미치는 석곡 열수추출물(DME)의 효과를 조사하였다. DME는 PMA와 Calcium ionophore 병행처리(PMACI)에 의해 유도되는 β-hexosaminidase 분비와 TNF-α, IL-4, HDC 발현을 현저히 억제하였다. 또한 PMACI에 의해 유도되는 NF-κB, AP-1 활성과 p38 kinase, extracellular signal-regulated kinase 1/2 (ERK1/2)과 c-Jun N-terminal kinase (JNK)의 인산화가 DME 전처리에 의해 저해되었다. 이러한 결과들은DME가 비만세포 탈과립을 억제하고, MAPKs/NF-κB/AP-1 신호전달 경로를 통해 TNF-α, IL-4, HDC 발현을 억제한다는 것을 시사한다. 본 연구결과들로 보아 DME는 과민반응과 염증성 질환을 치료하는 약물로 개발될 가능성을 가지는 것으로 사료된다.