• Fisheries and Aquatic Sciences
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• 제22권3호
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• pp.7.1-7.10
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• 2019

Sargassum serratifolium ethanolic extract has been known for strong antioxidant and anti-inflammatory properties. We prepared hexane fraction from the ethanolic extract of S. serratifolium (HSS) to improve biological activities. In this study, we investigated the effects of HSS on the inhibition of tumor necrosis factor (TNF)-${\alpha}$-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). We found that HSS suppressed the production of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in TNF-${\alpha}$-induced HUVECs. Moreover, TNF-${\alpha}$-induced production of monocyte chemoattractant protein 1 and keratinocyte chemoattractant was inhibited by HSS treatment. HSS suppressed TNF-${\alpha}$-induced nuclear factor kappa B ($NF-{\kappa}B$) activation via preventing proteolytic degradation of inhibitor ${\kappa}B-{\alpha}$. HSS induced the production of heme oxygenase 1 via translocation of Nrf2 into the nucleus in TNF-${\alpha}$-treated HUVECs. Overall, HSS alleviated vascular inflammation through the downregulation of $NF-{\kappa}B$ activation and the upregulation of Nrf2 activation in TNF-${\alpha}$-induced HUVECs. These results indicate that HSS may be used as therapeutic agents for vascular inflammatory disorders.

• 대한한방부인과학회지
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• 제34권3호
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• pp.29-48
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• 2021

Objectives: Banchong-san (BCS) is a herbal formula composed of 13 korean medicinal herbs and is traditionally used to treat inflammatory diseases and pain. The object of this study was to research the antioxidant, anti-inflammatory, antipruritic and antimicrobial effects of the BCS in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: In this experiment, effects of BCS on the following four were measured as follows: (1) Anti-oxidative effects were evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) Radical scavenging activity, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) Radical scavenging activity. (2) Anti-inflammatory effects were evaluated by the production amount of Reactive oxygen species (ROS), Nitric oxide (NO), Interleukin-1β (IL-1β), Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), Prostaglandin E2 (PGE₂), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)(the previous two are "mRNA"), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), inhibitor of nuclear factor kappa B (IκBα), nuclear factor kappa B (NF-κB) (the previous five are "Protein") in LPS-Stimulated RAW 264.7 cells. (3)Antipruritic effects were evaluated by the production amount of histamine, Leukotriene B4 (LTB4), LeukotrieneC4 (LTC4) Levels in phorbol 12-myristate 13-acetate(PMA)/ionomycin-stimulated MC/9 mast cell. (4) Anti-microbial effects were evaluated by the growth suppression of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Aspergillus niger. Results: The following results were obtained through each measurement: (1) DPPH Radical Scavenging Activity, ABTS Radical Scavenging Activity evoked a significant concentration-dependent increase. (2) ROS, NO, IL-1β, IL-6, TNF-α, PGE₂ production amount, iNOS, COX-2 mRNA expression were significantly reduced in the BCS extraction group compared with the control group and significantly decreased the amount of ERK, JNK, p38, NF-κB Protein expression. The amount of IκB-α Protein Expression have increased significantly. (3) The amounts of histamine, LTB4, LTC4 were significantly decreased. (4) The antibacterial efficacy, BCS inhibited the growth of Escherichia coli, Pseudomonas aeruginosa at concentrations of 5 ㎍/ml, but did not suppress the growth of staphylococcus aureus and aspergillus niger. Conclusions: The experimental results show that BCS has anti-oxidant, anti-inflammatory, antipruritic and antimicrobial properties.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.493-499
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• 2019

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

• Journal of Ginseng Research
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• 제45권3호
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• Fisheries and Aquatic Sciences
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• 제21권5호
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• pp.14.1-14.8
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• 2018

The objective of this study was to investigate the anti-inflammatory effects of the pepsinolytic hydrolysate from the fish frame, Johnius belengerii, on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The J. belengerii frame hydrolysate (JFH) significantly suppressed nitric oxide (NO) secretion on LPS-stimulated RAW264.7 macrophages. Moreover, the JFH markedly inhibited the levels of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the LPS-stimulated mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 was downregulated when cells were cultured with the JFH. The JFH significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK) and the translocation of nuclear factor-kappa B ($NF-{\kappa}B$) in macrophages. As the result, the JFH has the potential anti-inflammatory activity via blocking the JNK and $NF-{\kappa}B$ signal pathways.

• Journal of Microbiology and Biotechnology
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• 제32권8호
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• pp.1017-1025
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• 2022

Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.

• 한국미생물·생명공학회지
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• 제50권4호
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Journal of Applied Biological Chemistry
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• 제54권4호
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• pp.279-283
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• 2011

염증의 중요한 분자학적 기전에는 cyclooxygenase-2 (COX-2)에 의한 prostaglandins (PGs) 생성과 inducible nitric oxide synthase (iNOS)에 의한 nitric oxide (NO) 생성이 있다. 많은 종류의 박테리아나 바이러스가 전사요소인 nuclear factor-${\kappa}$B(NF-${\kappa}$B)를 활성화시켜 여러 타깃 유전자의 발현을 조절해 PGs나 NO와 같은 염증물질을 유도하게 된다. 우리는 이번 실험을 통하여 phenethyl isothiocyanate (PEITC)가 toll-like receptor(TLR) agonists에 의해 유도된 NF-${\kappa}$B활성과 COX-2, iNOS 발현에 어떠한 영향을 미치는지 알아 보았다. PEITC는 lipopolysaccharide (LPS)와 polyinosinic-polycytidylic acid (poly[I:C])에 의해 유도된 NF-${\kappa}$B활성을 억제시켰다. 또한 PEITC는 LPS와 Poly[I:C]에 의해 유도된 iNOS의 발현도 억제시켰다. 하지만 PEITC는 TLR agonists들인 LPS, Poly[I:C], 2 kDa macrophage-activating lipopeptide (MALP-2), oligodeoxynucleotide 1668 (ODN1668)에 의한 COX-2 발현은 억제시키지 못하였다. 즉 PEITC가 TRIF-dependent 신호전달체계만을 조절하여 TRIF-dependent 신호전달체계에 의해 조절되는 iNOS는 억제하지만 MyD88-dependent 신호전달 체계에 의해 조절되는 COX-2는 억제하지 못한다는 것을 설명해준다. 이러한 결과는 iNOS와 COX-2가 서로 다른 메커니즘에 의해 조절된다는 것을 암시하며, PEITC가 여러 병원균들로부터 유도되는 염증반응이나 만성적인 질병들을 조절할 수 있음을 제시하는 중요한 결과이다.

• 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.

• 대한본초학회지
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• 제30권6호
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• pp.33-38
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• 2015

Objectives : Portulaca oleracea (PO) have been used as a traditional medicine to treat inflammatory diseases in Korea. However, the anti-inflammatory effect of PO ethanol extract on lipopolysaccharide (LPS)-induced inflammation is not well-known. Therefore, this study was performed to identify the anti-inflammatory effect of PO on LPS induced inflammatory.Methods : Identification of PO was conducted by comparison with purified standards by HPLC. To measure out the cytotoxicity of PO, author performed the MTT assay. To evaluate the anti-inflammatory effects of PO, author examined the inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin, (IL)-1β and IL-6) on RAW 264.7 cells. Author also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot.Results : Three major components (peaks 1, 2, 3) were detected in both varieties and peak 1 was characterized as caffeic acid, peak 2 as p-coumaric acid, and peak 3 as ferulic acid by comparison of chromatographic properties with authentic standards. Extract from PO itself did not have any cytotoxic effect in RAW 264.7 cells. PO inhibited LPS-induced productions of inflammatory mediators such as NO and pro-inflammatory cytokines in RAW 264.7cells. In addition, PO inhibited the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun NH₂-terminal kinase (JNK) and NF-κB activation in RAW 264.7 cells.Conclusions : Above experiment data can be an important indicator for the identification of PO and this study suggest that treatment of PO could reduce the LPS-induced inflammation. Thereby, PO could be used as a protective agent against inflammation.