• Biomolecules & Therapeutics
• /
• v.24 no.1
• /
• pp.25-32
• /
• 2016

Lichens have been known to possess multiple biological activities, including anti-proliferative and anti-inflammatory activities. Vascular cell adhesion molecule-1 (VCAM-1) may play a role in the development of atherosclerosis. Hence, VCAM-1 is a possible therapeutic target in the treatment of the inflammatory disease. However, the effect of lobaric acid on VCAM-1 has not yet been investigated and characterized. For this study, we examined the effect of lobaric acid on the inhibition of VCAM-1 in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated mouse vascular smooth muscle cells. Western blot and ELISA showed that the increased expression of VCAM-1 by TNF-${\alpha}$ was significantly suppressed by the pre-treatment of lobaric acid ($0.1-10{\mu}g/ml$) for 2 h. Lobaric acid abrogated TNF-${\alpha}$-induced NF-${\kappa}B$ activity through preventing the degradation of $I{\kappa}B$ and phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein (MAP) kinase. Lobaric acid also inhibited the expression of TNF-${\alpha}$ receptor 1 (TNF-R1). Overall, our results suggest that lobaric acid inhibited VCAM-1 expression through the inhibition of p38, ERK, JNK and NF-${\kappa}B$ signaling pathways, and downregulation of TNF-R1 expression. Therefore, it is implicated that lobaric acid may suppress inflammation by altering the physiology of the atherosclerotic lesion.

• The Korea Journal of Herbology
• /
• v.26 no.3
• /
• pp.23-29
• /
• 2011

Objective : The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Scolopendrae Corpus (SC) on lipopolysaccharide (LPS)-induced inflammatory response. Methods : To evaluate the anti-inflammatory effects of SC, we examined the inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokines (TNF-a, inteleukin (IL)-$1{\beta}$ and IL-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and inhibitory kappa B a ($I{\kappa}$-Ba) using western blot. Furthermore, we also investigated the effect of SC on LPS-induced endotoxin shock. Results : Extract from SC itself had not any cytotoxic effect in RAW 264.7 cells. Aqueous extract from SC inhibited LPS-induced NO production and iNOS expression. SC pre-treatment also inhibited IL-$1{\beta}$, IL-6 production in RAW 264.7 cells. To investigate inhibitory effects of SC on inflammatory mediators, activation of MAPKs was examined. SC inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK) and also the degradation of $I{\kappa}$-$B{\alpha}$ in RAW 264.7 cells stimulated with LPS. Furthermore, SC administration reduced LPS-induced endotoxin shock. Conclusion : SC down-regulated LPS-induced production of inflammatory mediators through inhibition of activation of p38, JNK and degradation of $I{\kappa}$-$B{\alpha}$. Taken together, our results suggest that SC may be a beneficial drug against inflammatory diseases such as sepsis.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.5
• /
• pp.1315-1320
• /
• 2006

The root and rhizomes of Nardostachys chinensis belonging to the family Valerianaceae has been used for medicinal therapy in Korean traditional medicine. The parts have been especially used to elicit stomachic and sedative effects. Our previous studies reported that the water extract of N. chinensis has induced granulocytic differentiation inhuman promyelocytic leukemia (HL-60) cells. The Mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular responses, such as cell proliferation, differentiation and apoptosis. In this study, we investigated the signaling pathways on the HL-60 cell differentiation induced by N. chinensis. Activation of extracellular signal-regulated kinase (ERK) increased time-dependently in differentiation of HL-60 cells induced by N. chinersis. Activation of p38 increased slightly at 24 h after N. chinensis treatment, but activation of c-jun N-terminal kinase (JNK) was unaffected. Inhibitor of ERK (PD98059) significantly reduced NBT reduction activity induced by N. chinensis in HL-60 cells. In contrast, p38 inhibitor (SB203580) did not inhibit the cell differentiation. These results indicated that activaiton of ERK may De involved in HL-60 cell differentiation induced by N. chinensis.

• Nutrition Research and Practice
• /
• v.16 no.4
• /
• pp.435-449
• /
• 2022

BACKGROUND/OBJECTIVES: Cheonggukjang is a traditional fermented soybean paste with significant health-promoting effects. On the other hand, there have been insufficient studies on the safety and efficacy of Cheonggukjang, which is produced using traditional methods containing toxins and biogenic amines (BAs). This study compared the laxative effect of Cheonggukjang, containing high or low levels of toxins and BAs (HTBC or LTBC) in a loperamide (Lop)-induced constipation mouse model. MATERIALS/METHODS: To induce constipation, Lop (5 mg/kg) was administered orally to ICR mice twice a day for 4 days, and the dose was increased to 8 mg/kg after a 3-day rest period. Cheonggukjang (500 mg/kg, HTBC, or LTBC respectively) was administered for four weeks before the Lop treatment. RESULTS: The number of stools, fecal weight, water contents, gastrointestinal transit, and histological alterations were recovered significantly in the HTBC or LTBC groups. HTBC and LTBC administration did not induce significant changes in body weight, dietary intake, and behavior. The opioid-receptor downstream signaling pathway in colon tissues was also evaluated. The c-Kit, stem cell kinase, and mitogen-activated protein kinases subfamilies, including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinases, and p38, were all downregulated in the HTBC or LTBC-administered mice colon compared to the Lop group. CONCLUSION: These results show that Cheonggukjang, containing high levels of toxins and BAs, have a similar laxative effect in a mouse model of Lop-induced constipation.

• The Korean Journal of Pain
• /
• v.33 no.4
• /
• pp.335-343
• /
• 2020

Background: Zhongyi paste is a traditional Chinese medicine herbal paste that is externally applied to reduce inflammation and relieve pain. Methods: An acute foot swelling inflammation model in C57BL/6J mice was established by carrageenan-induced pathogenesis. Zhongyi paste raised the pain threshold and also reduced the degree of swelling in mice with carrageenan-induced foot swelling. Results: Analysis indicated that serum tumor necrosis factor-alpha, interleukin-1 beta, and prostaglandin E₂ (PGE₂) cytokine levels and PGE₂ levels in the paw tissue of the mice were decreased by Zhongyi paste treatment. The quantitative polymerase chain reaction and western blot results showed that Zhongyi paste downregulated the mRNA and protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2), and cyclooxygenase-2 (COX-2), and also downregulated the mRNA expression of PGE₂. At the same time, the Zhongyi paste exerted a stronger effect as an external drug than that of indomethacin, which is an oral drug, and voltaren, which is an externally applied drug. Conclusions: Our results indicated that Zhongyi paste is a very effective drug to reduce inflammatory swelling of the foot, and its mechanism of action is related to regulation of the ERK1/2-COX-2-PGE₂ pathway.

• BMB Reports
• /
• v.40 no.3
• /
• pp.325-332
• /
• 2007

The mitogen-activated protein kinase (MAPK) cascade is one of the major and evolutionally conserved signaling pathways and plays pivotal role in the regulation of stress and developmental signals in plants. Here, a novel gene, termed Gossypium hirsutum MAPK (GhMAPK), was isolated from cotton. The full-length cDNA of GhMAPK encodes for a 372 amino acid protein that contains all 11 of the MAPK conserved subdomains and the phosphorylationactivation motif, TEY. Amino acid sequence alignment revealed that GhMAPK shared high identity with group-C MAPK in plants and showed 83~89% similarities with MAPKs from Arabidopsis, apricot, pea, petunia, and tobacco. Southern blot analysis indicated that the GhMAPK belonged to a multygene family in cotton. Two introns were found within the region of genomic sequence. Northern blot analysis revealed that the transcripts of GhMAPK accumulated markedly when the cotton seedlings were subjected to various abiotic stimuli such as wounding, cold (4$^{\circ}C$), or salinity stress; Furthermore, GhMAPK was upregulated by the exogenous signaling molecules, such as salicylic acid (SA) and hydrogen peroxide ($H_2O_2C$), as well as pathogen attacks. These results indicate that the GhMAPK, which has a high degree of identity with group-C plant MAPKs, may also play an important role in response to environmental stresses.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.9
• /
• pp.1513-1517
• /
• 2013

This study examined the immunomodulatory activities of apple seed extracts (ASE). The immunomodulatory effects were estimated through nitric oxide production, cytokine induction, protein expression of inducible nitric oxide synthase (iNOS), and the phosphylation of mitogen-activated protein kinases (MAPKs) and inhibitory kappa $B{\alpha}$ ($I{\kappa}B-{\alpha}$) in the RAW 264.7 macrophage cell line. In the cytotoxicity asay, ASE (31 to $250{\mu}g/mL$) did not induce cytotoxicity; thus, the optimal concentration of ASE was confirmed to be less than $250{\mu}g/mL$. Nitric oxide (NO) and cytokines (tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6) production significantly increased in a dose-dependent manner. Similarly, the protein expression of iNOS and the phosphorylation of MAPKs and $I{\kappa}B-{\alpha}$ were also increased by ASE treatment. Overall, our results suggest that extracts from apple seeds potentially have immunomodulatory activities on macrophages.

• Journal of Ginseng Research
• /
• v.43 no.1
• /
• pp.95-104
• /
• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.1
• /
• pp.81-90
• /
• 2022

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

• Journal of Acupuncture Research
• /
• v.32 no.3
• /
• pp.69-81
• /
• 2015

Purpose : The first purpose of this study is to find out whether the water extract of Rehmanniae Radix Preparat(RRP), Cuscutae Semen(CS) and their combination(Ssangbohwan, SBH) have the effect of suppressing Receptor activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation. The second purpose of this study is to find out whether the water extract of RRP, CS and SBH have the effect of inhibiting osteoporosis in an osteoporosis model induced by lipopolysaccharide(LPS). Methods : After promoting differentiation of osteoclasts by treating the RANKL, we observed the effect by the administration of RRP, CS and SBH. In addition, by means of Reverse transcription polymerase chain reaction(RT-PCR), we assayed mRNA expression levels of NFATc1, c-Fos, TRAP and GAPDHS(Glyceraldehyde-3-phosphate dehydrogenase, spermatogeni) from bone marrow macrophages(BMMs). Similarly, the protein expression levels of NFATc1 (Nuclear factor of activated T-cells, cytoplasmic1), C-Fos, MAPKs(Mitogen-activated protein kinases) and ${\beta}$-actin in cell lysates were analyzed by means of Western Blotting. Finally, we determined the anti-osteoporotic effects of RRP, CS and SBH, through the use of Lipopolysaccharide-induced bone-loss mouse. Results : RRP, CS and SBH showed remarkable inhibitive effect on RANKL-treated osteoclast differentiation without cytotoxicity. SBH inhibited the phosphorylation of p38, Jun N-terminal kinases(JNK), and I-${\kappa}B$ and down-regulated the induction of c-Fos and NFATc1 by RANKL. RRP, CS suppressed degradation of I-${\kappa}B$, but it did not affect c-Fos and NFATc1 by RANKL. Lastly, in vivo data showed that RRP and SBH prevented bone erosion by LPS treatment. Conclusions : These results demonstrate SBH can be effective remedy for bone-loss diseases such as osteoporosis.