• BMB Reports
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• 제45권12호
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• pp.724-729
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• 2012

In this study, we evaluated the anti-melanogenesis effects of Caffeoylserotonin (CaS) in B16 melanoma cells. Treatment with CaS reduced the melanin content and tyrosinase (TYR) activity in B16 melanoma cells in a dose-dependent manner. CaS inhibited the expression of melanogenesis-related proteins, including microphthalmia-associated transcription factor (MITF), TYR, and tyrosinase-related protein-1 (TRP-1), but not TRP-2. ${\alpha}$-MSH is known to interact with melanocortin 1 receptor (MC1R) thus activating adenylyl cyclase and increasing intracellular cyclic AMP (cAMP) levels. Furthermore, cAMP activates extracellular signal-regulated kinase 2 (ERK2) via phosphorylation, which phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. The CaS reduced intracellular cAMP levels to unstimulated levels and activated ERK phosphorylation within 30 min. The ERK inhibitor PD98059 abrogated the suppressive effect of CaS on ${\alpha}$-MSH-induced melanogenesis. Based on this study, the inhibitory effects of CaS on melanogenesis are derived from the downregulation of MITF signaling via the inhibition of intracellular cAMP levels, as well as acceleration of ERK activation.

• Journal of Ginseng Research
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• 제41권1호
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• pp.96-102
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• 2017

Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

• 셀메드
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• 제6권4호
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• pp.23.1-23.6
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• 2016

With the rapid developments in nanotechnology, an increasing number of nanomaterials have been applied in various aspects of our lives. Recently, pharmaceutical nanotechnology with numerous advantages has growingly attracted the attention of many researchers. Zinc oxide nanoparticles (ZnO-NPs) are nanomaterials that are widely used in many fields including diagnostics, therapeutics, drug-delivery systems, electronics, cosmetics, sunscreens, coatings, ceramic products, paints, and food additives, due to their magnetic, catalytic, semiconducting, anti-cancer, anti-bacterial, anti-inflammatory, ultraviolet-protective, and binding properties. The present review focused on the recent research works concerning role of ZnO-NP on inflammation. Several studies have reported that ZnO-NP induces inflammatory reaction through the generation of reactive oxygen species by oxidative stress and production of inflammatory cytokines by activation of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$). Meanwhile, other researchers reported that ZnO-NP exhibits an anti-inflammatory effect by inhibiting the up-regulation of inflammatory cytokines and the activation of $NF-{\kappa}B$, caspase-1, $I{\kappa}B$ $kinase{\beta}$, receptor interacting protein2, and extracellular signal-regulated kinase. Previous studies reported that size and shape of nanoparticles, surfactants used for nanoparticles protection, medium, and experimental conditions can also affect cellular signal pathway. This review indicated that the anti-inflammatory effectiveness of ZnO-NP was determined by the nanoparticle size as well as various experimental conditions. Therefore, the author suggests that pharmaceutical therapy with the ZnO-NP is one of the possible strategies to overcome the inflammatory reactions. However, further studies should be performed to maximize the anti-inflammatory effect of ZnO-NP to apply as a potential agent in biomedical applications.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권6호
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• pp.556-563
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• 2005

Homogentisic acid was found to scavenge intracellular reactive oxygen species (ROS), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and thus prevented lipid peroxidation in human fibroblast (Wl 38) cells. The radical scavenging activity of homogentisic acid was found to protect Wl 38 cells against hydrogen peroxide $(H_2O_2)$ induced oxidative stress, via the activation of extracellular signal regulated kinase (ERK) protein. Homogentisic acid increased the activity of catalase. Hence, from the present study, it is suggested that homogentisic acid protects Wl 38 cells against $H_2O_2$ damage by enhancing the intracellular antioxidative activity.

• BMB Reports
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• 제46권12호
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• pp.594-599
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• 2013

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.43-48
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• 2012

Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-$3{\beta}$ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

• 한국축산식품학회지
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• 제42권6호
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• pp.1031-1045
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• 2022

Postbiotics are defined as probiotics inactivated by heat, ultraviolet radiation, sonication, and other physical or chemical stresses. Postbiotics are more stable than probiotics, and these properties are advantageous for food additives and pharmacological agents. This study investigated the immunostimulatory effects of heat-treated Lactiplantibacillus plantarum LM1004 (HT-LM1004). Cellular fatty acid composition of L. plantarum LM1004 isolated form kimchi was analyzed by gas chromatography-mass spectrometry detection system. The nitric oxide (NO) content was estimated using Griess reagent. Immunostimulatory cytokines were evaluated using enzyme-linked immunosorbent assay. Relative protein expressions were evaluated by western blotting. Phagocytosis was measured using enzyme-labelled Escherichia coli particles. L. plantarum LM1004 showed 7 kinds of cellular fatty acids including palmitic acid (C16:0). The HT-LM1004 induced release of NO and upregulated the inducible NO synthase in RAW 264.7 macrophage cells. Tumor necrosis factor-α and interleukin-6 levels were also increased compared to control (non-treated macrophages). Furthermore, HT-LM1004 modulated mitogen-activated protein kinase (MAPK) subfamilies including p38 MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase. Therefore, these immunostimulatory effects were attributed to the production of transcriptional factors, such as nuclear factor kappa B (NF-κB) and the activator protein 1 family (AP-1). However, HT-LM1004 did not showed significant phagocytosis of RAW 264.7 macrophage cells. Overall, HT-LM1004 stimulated MAPK/AP-1 and NF-κB expression, resulting in the release of NO and cytokines. These results will contribute to the development of diverse types of food and pharmacological products for immunostimulatory agents with postbiotics.

• Journal of Acupuncture Research
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• 제40권4호
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• pp.368-376
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• 2023

Background: Although bee venom (BV) has clinical benefits in osteoarthritis and rheumatoid arthritis, it has not been tested as treatment for gouty arthritis. Moreover, in vitro, BV has been proven to exhibit anti-inflammatory and positive effects on osteoarthritis, but only limited evidence can confirm its beneficial effects on gout. Thus, this study aims to assess the anti-inflammatory effects of BV on monosodium urate (MSU)-induced THP-1 monocytes. Methods: THP-1 monocytes were differentiated into mature macrophages using phorbol 12-myristate 13-acetate (PMA) and pretreated for 6 hours with BV and a Caspase-1 inhibitor in a physiologically achievable range of concentrations (BV, 0.1-1 ㎍/mL; Caspase-1 inhibitor, 1-10 μM), followed by MSU crystal stimulation for 24 hours. The secretions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) were increased in the MSU crystal-stimulated THP-1 cells. Results: Caspase-1 inhibitors suppressed the production of all mediators in a dose-dependent manner. BV worked on equal terms with Caspase-1 inhibitors and showed more satisfactory effects on TNF-α, PGE2, COX-2, and inducible nitric oxide synthase (iNOS). Moreover, the western blot analysis revealed that BV regulated the transcriptional levels of these mediators via the suppression of extracellular signal-regulated kinase (ERK) pathway activation. Conclusion: The results of the present study clearly suggest that BV inhibits MSU-induced inflammation in vitro, suggesting a possible role for BV in gout treatment.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.229-236
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• 2016

Resveratrol (RSV) may provide numerous protective effects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the effects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, $p47^{phox}$, Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced $NF-{\kappa}B$ activation by promoting $I{\kappa}B-{\alpha}$ degradation. Meanwhile, the observed increases in nuclear $NF-{\kappa}B$, NOX4, $p47^{phox}$, and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting $NF-{\kappa}B$ activation.

• KSBB Journal
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• 제28권1호
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• pp.7-12
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• 2013

Thromboxane $A_2$ ($TXA_2$) is one of major proinflammatory mediators, plays an important role in the development of vascular inflammatory diseases. $TXA_2$ acting through the thromboxane receptor regulates multiple pathways and genes in a variety of cells. In this study, we report that the activation of thromboxane receptor with U46619 increases the interleukin-8 (IL-8) mRNA in vascular endothelial cells. We also demonstrated that U46619 produces the activations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK), which is required for endothelial IL-8 production. And U46619 enhanced mRNA stability of IL-8 transcripts in endothelial cells. Moreover, inhibition of ERK1/2 or p38MAPK reduced monocyte adhesion to aortic endothelium stimulated by U46619. Therefore, these results suggest that activation of thromboxane receptor promotes the expression of IL-8 via ERK1/2 and p38MAPK activation in endothelial cells.