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1.
Reg Anesth Pain Med ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38991713

ABSTRACT

BACKGROUND: This cadaveric study aimed to analyze injectate spread to target nerves during a single-injection, ultrasound-guided intertransverse process block. METHODS: An ultrasound-guided intertransverse process block with three different injectate volumes was administered to 12 cadavers. Each hemithorax was subjected to computer-generated random allocation of 10, 15, or 20 mL ultrasound-guided, single-injection intertransverse process block at the T2 vertebral level. Latex dye solution was injected into each hemithorax in accordance with the allocated volume. The presence of dye at the nerve root in the sympathetic chain and intercostal nerves at various injection levels was examined via dissection. RESULTS: Injectate spread into the dorsal rami was observed in seven of eight (87.5%), seven of eight (87.5%), and all eight (100%) of the 10, 15, and 20 mL specimens, respectively. In all 20 mL specimens, consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion was observed. CONCLUSIONS: An injectate volume of 20 mL was required for consistent staining of the dorsal rami, spinal nerve, and dorsal root ganglion in an intertransverse process block. Although an augmented injectate volume was associated with an increased likelihood of target nerve staining, consistent staining of the sympathetic ganglion, rami communicans, and ventral ramus was not observed, even at a volume of 20 mL. The current study presents initial findings suggesting that as opposed to a sympathetic ganglion block, a 20 mL intertransverse process block may act as a feasible substitute for dorsal root ganglion, spinal nerve, and medial branch blocks within a clinical context.

2.
Biomol Ther (Seoul) ; 32(1): 136-145, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37424516

ABSTRACT

People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-ß-modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4+T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-ß-dependent manner and induces CD4+T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-ß and inhibit CD4+T cell proliferation, directly regulated Treg differentiation from CD4+T cells. These results indicate that the IF regimen enhances the TGF-ß-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.

3.
Prev Nutr Food Sci ; 28(3): 263-270, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37842245

ABSTRACT

In this study, immature persimmon (Diospyros kaki Thunb.) ethanol extract was administered to an obese animal model fed a high-fat diet to measure weight change, adipose tissue weight, serum lipid level, and expression level of adipose-related genes to evaluate its efficacy. Administration of D. kaki ethanol extract (DKE) (100 and 500 mg/kg/d) decreased the body weight gain, adipose tissue weight, and serum triglyceride levels in mice fed a high-fat diet. Furthermore, it improved the leptin and adiponectin levels in the blood as well as gene expression in the liver. It also inhibited the expression of sterol regulatory element-binding protein-1c, inhibiting the production of triglyceride biosynthetic enzyme fatty acid synthesis and acetyl-CoA carboxylase, and decreased the expressions of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins that induce adipocyte differentiation. Therefore, these data suggest that DKE exerts beneficial effects on high-fat diet-induced obesity by modulating lipid metabolism in mice fed a high-fat diet.

4.
Nutrients ; 14(24)2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36558517

ABSTRACT

Hair loss remains a significant problem that is difficult to treat; therefore, there is a need to identify safe natural materials that can help patients with hair loss. We evaluated the hair anagen activation effects of limonin, which is abundant in immature citrus fruits. Limonin increased the proliferation of rat dermal papilla cells (rDPC) by changing the levels of cyclin D1 and p27, and increasing the number of BrdU-positive cells. Limonin increased autophagy by decreasing phosphorylated mammalian target of rapamycin levels and increasing the phospho-Raptor, ATG7 and LC3B. Limonin also activated the Wnt/ß-catenin pathway by increasing phospho-ß-catenin levels. XAV939, a Wnt/ß-catenin inhibitor, inhibited these limonin-induced changes, including induced autophagy, BrdU-positive cells, and cell proliferation. Limonin increased the phosphorylated AKT levels in both two-dimensional cultured rDPC and three-dimensional spheroids. Treatment with the PI3K inhibitor wortmannin inhibited limonin-induced proliferation, and disrupted other limonin-mediated changes, including decreased p27, increased BrdU-positive cells, induced autophagy, and increased ATG7 and LC3B levels. Wortmannin also inhibited limonin-induced cyclin D1 and LC3 expression in spheroids. Collectively, these results indicate that limonin can enhance anagen signaling by activating autophagy via targeting the Wnt/ß-catenin and/or PI3K/AKT pathways in rDPC, highlighting a candidate nutrient for hair loss treatment.


Subject(s)
Hair Follicle , Limonins , Animals , Rats , Alopecia , beta Catenin/metabolism , Bromodeoxyuridine/metabolism , Cell Proliferation , Cells, Cultured , Cyclin D1/metabolism , Fruit/metabolism , Limonins/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Wnt Signaling Pathway , Wortmannin/metabolism , Wortmannin/pharmacology
5.
Molecules ; 27(7)2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35408575

ABSTRACT

Various studies addressing the increasing problem of hair loss, using natural products with few side effects, have been conducted. 5-bromo-3,4-dihydroxybenzaldehyde (BDB) exhibited anti-inflammatory effects in mouse models of atopic dermatitis and inhibited UVB-induced oxidative stress in keratinocytes. Here, we investigated its stimulating effect and the underlying mechanism of action on hair growth using rat vibrissa follicles and dermal papilla cells (DPCs), required for the regulation of hair cycle and length. BDB increased the length of hair fibers in rat vibrissa follicles and the proliferation of DPCs, along with causing changes in the levels of cell cycle-related proteins. We investigated whether BDB could trigger anagen-activating signaling pathways, such as the Wnt/ß-catenin pathway and autophagy in DPCs. BDB induces activation of the Wnt/ß-catenin pathway through the phosphorylation of GSG3ß and ß-catenin. BDB increased the levels of autophagic vacuoles and autophagy regulatory proteins Atg7, Atg5, Atg16L, and LC3B. We also investigated whether BDB inhibits the TGF-ß pathway, which promotes transition to the catagen phase. BDB inhibited the phosphorylation of Smad2 induced by TGF-ß1. Thus, BDB can promote hair growth by modulating anagen signaling by activating Wnt/ß-catenin and autophagy pathways and inhibiting the TGF-ß pathway in DPCs.


Subject(s)
Benzaldehydes , Hair , Transforming Growth Factor beta , Wnt Signaling Pathway , Animals , Autophagy , Benzaldehydes/pharmacology , Cell Cycle Proteins/metabolism , Cell Proliferation , Cells, Cultured , Hair/growth & development , Hair Follicle/metabolism , Rats , Transforming Growth Factor beta/metabolism , beta Catenin/metabolism
6.
Sensors (Basel) ; 22(6)2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35336489

ABSTRACT

When we develop wearable assistive devices, comfort and support are two main issues that need to be considered. In conventional design approaches, the degree of freedom of the wearer's joint movements tends to be oversimplified. Accordingly, the wearer's motion becomes restrained and bone/ligament injuries might occur in case of an unexpected fall. To mitigate these issues, this paper proposes a novel joint link mechanism inspired by a human spine structure as well as functionalities. The key feature of the proposed spine-like joint link mechanism is that hemispherical blocks are concatenated via flexible synthetic fiber lines so that their concatenation stiffness can be adjusted according to a tensile force. This feature has a great potentiality for designing a wearable assistive device that can support aged people's sit-to-stand action or augment spinal motion by regulating the concatenation stiffness. In addition, the concatenated hemispherical blocks enable the wearer to move his/her joint with full freedom, which in turn increases the wearer's mobility and prevents joint misalignment. The experimental results with a testbed and a pilot wearer substantiated that the spine-like joint link mechanism can serve as a key component in the design of wearable assistive devices for better mobility.


Subject(s)
Self-Help Devices , Wearable Electronic Devices , Accidental Falls , Aged , Female , Humans , Male , Movement/physiology , Spine
7.
Toxicol Res ; 35(3): 279-285, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31341557

ABSTRACT

In this study, we investigated the therapeutic potential of Cinnamomum camphora leaves on allergic skin inflammation such as atopic dermatitis. We evaluated the effects of C. camphora leaves on human adult low-calcium high-temperature keratinocytes and atopic dermatitis mice. C. camphora leaves inhibited Macrophage-derived chemokine (an inflammatory chemokine) production in interferon-γ (10 ng/mL) stimulated Human adult low-calcium high-temperature keratinocytes in a dose dependent manner. C. camphora leaves suppressed the phosphorylation of janus kinase signal transducer and activator of transcription 1. C. camphora leaves also suppressed the phosphorylation of extracellular signal-regulated kinase 1/2, a central signaling molecule in the inflammation process. These results suggest that C. camphora leaves exhibits anti-inflammatory effect via the phosphorylation of signal transducer and activator of transcription 1 and extracellular signal-regulated kinase 1/2. To study the advanced effects of C. camphora leaves on atopic dermatitis, we induced experimental atopic dermatitis in mice by applying 2,4-dinitrochlorobenzene. The group treated with C. camphora leaves (100 mg/kg) showed remarkable improvement of atopic dermatitis symptoms: reduced serum immunoglobulin E levels, smaller lymph nodes with reduced thickness and length, decreased ear edema, and reduced levels of inflammatory cell infiltration in the ears. Interestingly, the effects of C. camphora leaves on atopic dermatitis symptoms were stronger than those of hydrocort cream, a positive control. Taken together, C. camphora leaves showed alleviating effects on the inflammatory chemokine production in vitro and atopic dermatitis symptoms in vivo. These results suggest that C. camphora leaves help in the treatment of allergic inflammation such as atopic dermatitis.

9.
Toxicol Res ; 33(4): 325-332, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29071017

ABSTRACT

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 µM) 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-κB) 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.

10.
Clin Exp Reprod Med ; 44(4): 207-213, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29376018

ABSTRACT

OBJECTIVE: This study investigated the prevalence of infections with human papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium in the semen of Korean infertile couples and their associations with sperm quality. METHODS: Semen specimens were collected from 400 men who underwent a fertility evaluation. Infection with above five pathogens was assessed in each specimen. Sperm quality was compared in the pathogen-infected group and the non-infected group. RESULTS: The infection rates of human papillomavirus, C. trachomatis, U. urealyticum, M. hominis, and M. genitalium in the study subjects were 1.57%, 0.79%, 16.80%, 4.46%, and 1.31%, respectively. The rate of morphological normality in the U. urealyticum-infected group was significantly lower than in those not infected with U. urealyticum. In a subgroup analysis of normozoospermic samples, the semen volume and the total sperm count in the pathogen-infected group were significantly lower than in the non-infected group. CONCLUSION: Our results suggest that infection with U. urealyticum alone and any of the five sexually transmitted infections are likely to affect sperm morphology and semen volume, respectively.

11.
Toxicol Res ; 32(2): 109-14, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27123161

ABSTRACT

Allergic skin inflammation such as atopic dermatitis is characterized by skin barrier dysfunction, edema, and infiltration with various inflammatory cells. The anti-inflammatory effects of Apo-9'-fucoxanthinone, isolated from Sargassum muticum, have been described in many diseases, but the mechanism by which it modulates the immune system is poorly understood. In this study, the ability of Apo-9'-fucoxanthinone to suppress allergic reactions was investigated using a mouse model of atopic dermatitis. The Apo-9'-fucoxanthinone-treated group showed significantly decreased immunoglobulin E in serum. Also, Apo-9'-fucoxanthinone treatment resulted in a smaller lymph node size with reduced the thickness and length compared to the induction group. In addition, Apo-9'-fucoxanthinone inhibited the expression of interleukin-4, interferon-gamma and tumor necrosis factor-alpha by phorbol 12-myristate 13-acetate and ionomycin-stimulated lymphocytes. These results suggest that Apo-9'-fucoxanthinone may be a useful therapeutic strategy for treating chronic inflammatory diseases.

12.
Biomol Ther (Seoul) ; 23(3): 238-44, 2015 May.
Article in English | MEDLINE | ID: mdl-25995822

ABSTRACT

Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-γ (IFN-γ)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-γ (10 ng/mL) in a dose dependent manner. Dieckol (5 and 10 µM) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.

13.
PLoS One ; 10(4): e0116709, 2015.
Article in English | MEDLINE | ID: mdl-25849359

ABSTRACT

A smart-card-based user authentication scheme for wireless sensor networks (hereafter referred to as a SCA-WSN scheme) is designed to ensure that only users who possess both a smart card and the corresponding password are allowed to gain access to sensor data and their transmissions. Despite many research efforts in recent years, it remains a challenging task to design an efficient SCA-WSN scheme that achieves user anonymity. The majority of published SCA-WSN schemes use only lightweight cryptographic techniques (rather than public-key cryptographic techniques) for the sake of efficiency, and have been demonstrated to suffer from the inability to provide user anonymity. Some schemes employ elliptic curve cryptography for better security but require sensors with strict resource constraints to perform computationally expensive scalar-point multiplications; despite the increased computational requirements, these schemes do not provide user anonymity. In this paper, we present a new SCA-WSN scheme that not only achieves user anonymity but also is efficient in terms of the computation loads for sensors. Our scheme employs elliptic curve cryptography but restricts its use only to anonymous user-to-gateway authentication, thereby allowing sensors to perform only lightweight cryptographic operations. Our scheme also enjoys provable security in a formal model extended from the widely accepted Bellare-Pointcheval-Rogaway (2000) model to capture the user anonymity property and various SCA-WSN specific attacks (e.g., stolen smart card attacks, node capture attacks, privileged insider attacks, and stolen verifier attacks).


Subject(s)
Algorithms , Computer Communication Networks/instrumentation , Computer Security/instrumentation , Models, Theoretical , Wireless Technology/instrumentation , Confidentiality , Health Smart Cards , Humans
14.
Mar Drugs ; 13(4): 2141-57, 2015 Apr 13.
Article in English | MEDLINE | ID: mdl-25871292

ABSTRACT

Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishige okamuarae, a brown alga. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that DPHC strongly reduces the production of interleukin 6 (IL-6), but not that of tumor necrosis factor-alpha (TNF-α) induced by LPS. DPHC (12.5 and 100 µM) suppressed the phosphorylation and the nuclear translocation of NF-kappaB (NF-κB), a central signaling molecule in the inflammation process induced by LPS. The suppressor of cytokine signaling 1 (SOCS1) is a negative feedback regulator of Janus kinase (Jak)-signal transducer and activator of transcription (STAT) signaling. In this study, DPHC inhibited STAT5 expression and upregulated that of SOCS1 at a concentration of 100 µM. Furthermore, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) (a specific NF-κB inhibitor) and JI (a specific Jak2 inhibitor) reduced the production of IL-6, but not that of tumor necrosis factor-alpha (TNF-α) in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that DPHC inhibits IL-6 production via the downregulation of NF-κB and Jak2-STAT5 pathway and upregulation of SOCS1.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Heterocyclic Compounds, 3-Ring/pharmacology , Interleukin-6/antagonists & inhibitors , Macrophages/drug effects , NF-kappa B/antagonists & inhibitors , STAT5 Transcription Factor/antagonists & inhibitors , Suppressor of Cytokine Signaling Proteins/agonists , Administration, Cutaneous , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Dermatitis, Atopic/prevention & control , Dose-Response Relationship, Drug , Female , Gene Expression Regulation/drug effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Heterocyclic Compounds, 3-Ring/isolation & purification , Heterocyclic Compounds, 3-Ring/therapeutic use , Interleukin-6/metabolism , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/toxicity , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Pacific Ocean , Phaeophyceae/chemistry , Phaeophyceae/growth & development , RAW 264.7 Cells , Republic of Korea , STAT5 Transcription Factor/genetics , STAT5 Transcription Factor/metabolism , Skin/drug effects , Skin/immunology , Skin/pathology , Specific Pathogen-Free Organisms , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins/antagonists & inhibitors , Suppressor of Cytokine Signaling Proteins/genetics , Suppressor of Cytokine Signaling Proteins/metabolism
15.
J Invest Dermatol ; 135(6): 1556-1564, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25405323

ABSTRACT

Regulatory T cells (Tregs) have key roles in the immune response by suppressing the differentiation and proliferation of various immune cells. The beneficial effects of docosahexaenoic acid (DHA) have been described for many diseases; however, the mechanism by which it modulates the immune system is poorly understood. Therefore, the aim of this study was to examine whether DHA suppresses allergic reactions and upregulates the generation of CD4(+)Foxp3(+) T cells. We also examined the effects of transfusing interleukin-10/transforming growth factor-ß (TGF-ß)-modified macrophages (M2 macrophages) treated with DHA into a mouse model of atopic dermatitis. Here, we show that administration of DHA upregulates the generation of TGF-ß-dependent CD4(+) forkhead box protein 3 (Foxp3(+)) Tregs. DHA induced T-cell hypo-responsiveness and downregulated cytokines associated with T helper (Th)-1, Th2, and Th17 cells. The differentiation of Foxp3(+) Tregs into CD4(+) T cells was directly mediated by DHA-M2 macrophages, which deactivated effector macrophages and inhibited CD4(+) T-cell proliferation. DHA showed therapeutic effects in mice with experimental atopic dermatitis. These results show that DHA enhances the function of M2 macrophages and that the generation of Tregs effectively protects mice against an inflammatory immune disorder. Thus, DHA may be a useful therapeutic strategy for treating chronic inflammatory diseases.


Subject(s)
Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/immunology , Docosahexaenoic Acids/chemistry , Interleukin-10/immunology , Macrophages/immunology , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta1/immunology , Animals , Cell Differentiation/drug effects , Forkhead Transcription Factors/metabolism , Gene Expression Regulation , Inflammation , Macrophages/drug effects , Mice , Mice, Inbred BALB C , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology
16.
Chem Pharm Bull (Tokyo) ; 61(10): 1002-8, 2013.
Article in English | MEDLINE | ID: mdl-24088692

ABSTRACT

Jasmonates are lipid-based stress hormones that are critical for the defense of plants against insects. Two naturally occurring jasmonates, jasmonic acid and methyl jasmonate, have recently been explored for their efficacy as anti-cancer agents. Furthermore, certain synthetic jasmonates (e.g., the cyclopentenone isoprostane J2) exert anti-inflammatory actions in lipopolysaccharide (LPS)-challenged murine macrophages via down-regulation of chemokines and other inflammatory mediators. Chemokines participate in the development and progression of many inflammatory disorders, such as atopic dermatitis (AD) and Crohn's disease, as exemplified by the role of macrophage-derived chemokine (MDC/CCL22) in the pathology of AD. The current study therefore investigated the impact of jasmonate derivatives (jasmonic acid and methyl jasmonate) and their synthetic analogues (J2 and J7) on the expression of MDC in interferon (IFN)-γ- and tumor necrosis factor (TNF)-α-stimulated HaCaT human keratinocytes, as well as the attendant mechanism of action. Jasmonic acid, methyl jasmonate, and J2 failed to inhibit the cytokine-stimulated production of MDC. By contrast, J7 suppressed the mRNA and protein expression levels of MDC in a dose-dependent manner. Moreover, J7 diminished the activation of signal transducers and activators of transcription 1 (STAT1), but had no inhibitory effect on the nuclear factor kappa B (NF-κB) or mitogen-activated protein kinase (MAPK) pathways. These results demonstrate that J7 impairs IFN-γ- and TNF-α-induced inflammatory chemokine production by targeting the STAT1 pathway.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/toxicity , Chemokines/metabolism , Cyclopentanes/chemistry , Cyclopentanes/pharmacology , Down-Regulation/drug effects , Fatty Acids, Unsaturated/chemistry , Oxylipins/pharmacology , STAT1 Transcription Factor/metabolism , Animals , Anti-Inflammatory Agents/chemistry , Antineoplastic Agents/chemistry , Cell Line , Cell Survival/drug effects , Chemokines/genetics , Fatty Acids, Unsaturated/pharmacology , Humans , Inflammation Mediators/metabolism , Interferon-gamma/pharmacology , Keratinocytes/drug effects , Keratinocytes/metabolism , Lipopolysaccharides/toxicity , Macrophages/drug effects , Macrophages/metabolism , Mice , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Oxylipins/chemistry , RNA, Messenger/metabolism , STAT1 Transcription Factor/agonists , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/pharmacology
17.
Biomol Ther (Seoul) ; 21(2): 138-45, 2013 Mar.
Article in English | MEDLINE | ID: mdl-24009872

ABSTRACT

Citrus fruit contain various flavonoids that have multiple biological activities. However, the content of these flavonoids are changed during maturation and immature Citrus is known to contain larger amounts than mature. Chemokines are significant mediators for cell migration, while thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well known as the typical inflammatory chemokines in atopic dermatitis (AD), a pruritic and chronic inflammatory skin disease. We reported recently that the EtOH extract of immature Citrus unshiu inhibits TARC and MDC production. Therefore, we investigated the activity of flavonoids contained in immature Citrus on TARC and MDC levels. As a result, among the various flavonoids, quercetagetin has stronger inhibitory effects on the protein and mRNA expression of TARC and MDC than other flavonoids. Quercetagetin particularly has better activity on TARC and MDC level than quercetin. In HPLC analysis, the standard peak of quercetagetin matches the peaks of extract of immature C. unshiu. This suggests that quercetagetin is an anti-inflammatory component in immature C. unshiu.

18.
Biochem Biophys Res Commun ; 434(4): 892-7, 2013 May 17.
Article in English | MEDLINE | ID: mdl-23611776

ABSTRACT

Inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Sargachromanol G (SG), isolated from the brown alga Sargassum siliquastrum, inhibits the production of inflammatory cytokines. In the present study, we determined the effect of SG on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. SG inhibited RANKL-induced osteoclast differentiation from RAW264.7 cells without signs of cytotoxicity. Additionally, the expression of osteoclastic marker genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), matrix metalloproteinase 9 (MMP9), and calcitonin receptor (CTR), was strongly inhibited. SG inhibited RANKL-induced activation of NF-κB by suppressing RANKL-mediated IκB-α degradation. Furthermore, SG inhibited RANKL-induced phosphorylation of mitogen activated protein kinases (p38, JNK, and ERK). This study identified SG as an inhibitor for osteoclast formation and provided evidence that natural compounds, such as SG, are an alternative medicines for preventing and treating osteolysis.


Subject(s)
Benzopyrans/pharmacology , Macrophages/drug effects , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Osteoclasts/drug effects , RANK Ligand/pharmacology , Acid Phosphatase/genetics , Acid Phosphatase/metabolism , Animals , Cathepsin K/genetics , Cathepsin K/metabolism , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Gene Expression/drug effects , I-kappa B Proteins/metabolism , Immunoblotting , Isoenzymes/genetics , Isoenzymes/metabolism , Macrophages/cytology , Macrophages/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Mitogen-Activated Protein Kinase 8/metabolism , NF-KappaB Inhibitor alpha , Osteoclasts/cytology , Osteoclasts/metabolism , Phosphorylation/drug effects , Receptors, Calcitonin/genetics , Receptors, Calcitonin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tartrate-Resistant Acid Phosphatase , p38 Mitogen-Activated Protein Kinases/metabolism
19.
Immunopharmacol Immunotoxicol ; 35(1): 80-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22758221

ABSTRACT

Nitric oxide (NO) is a crucial molecule in inflammatory diseases and is synthesized from L-arginine by a specific enzyme, NO synthase (NOS). The expression of inducible NOS (iNOS) is activated in macrophages by various stimuli, such as lipopolysaccharide (LPS), a wall component of gram-negative bacteria. LPS binds to toll-like receptor 4 (TLR4) on the macrophage surface and activates several downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways. This study investigated whether sargaquinoic acid isolated from Sargassum siliquastrum might have anti-inflammatory activity and interfere with NO production in macrophages by disrupting LPS-induced signaling. This study was conducted in vitro using RAW264.7 murine macrophages. LPS-stimulated cells were treated with sargaquinoic acid, and the effects on NO production, iNOS expression, and involvement of the NF-κB signaling pathway were investigated by Griess assay, western blotting, and confocal microscopy. The results demonstrated that sargaquinoic acid inhibited the production of NO and the expression of the iNOS protein in LPS-stimulated RAW264.7 macrophages. Moreover, sargaquinoic acid inhibited the degradation of inhibitory-κB protein (IκB)-α and the nuclear translocation of NF-κB, a key transcription factor for the regulation of iNOS expression. Also, sargaquinoic acid influenced the phosphorylation of JNK1/2 MAPK, except ERK1/2 and p38 MAPKs, stimulated by LPS. These results suggest that sargaquinoic acid specifically prevents NO production in macrophages via the blockade of NF-κB activation and may thus have therapeutic applications in various inflammatory diseases.


Subject(s)
Alkenes/pharmacology , Benzoquinones/pharmacology , JNK Mitogen-Activated Protein Kinases/metabolism , Macrophages/drug effects , NF-kappa B/metabolism , Nitric Oxide/biosynthesis , Sargassum/chemistry , Animals , Anti-Inflammatory Agents/pharmacology , Cell Line , Cell Survival/drug effects , I-kappa B Proteins/metabolism , Lipopolysaccharides/pharmacology , MAP Kinase Signaling System/drug effects , Macrophages/metabolism , Mice , Mitogen-Activated Protein Kinase 8/metabolism , Mitogen-Activated Protein Kinase 9/metabolism , Mitogen-Activated Protein Kinases/metabolism , NF-KappaB Inhibitor alpha , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Phosphorylation/drug effects , STAT1 Transcription Factor/metabolism , Signal Transduction/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
20.
Arch Pharm Res ; 35(8): 1421-30, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22941485

ABSTRACT

A study on the anti-inflammatory activity of brown alga Sargassum siliquastrum led to the isolation of sargachromanol G (SG). In this study, the anti-inflammatory effect and the action mechanism of SG have been investigated in murine macrophage cell line RAW 264.7. SG dosedependently inhibited the production of inflammatory markers [nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E(2) (PGE(2)), and cyclooxygenase-2 (COX-2)] and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6] induced by LPS treatment. To further elucidate the mechanism of this inhibitory effect of SG, we studied LPS-induced nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinases (MAPKs) phosphorylation. SG inhibited the phosphorylation IκB-α and NF-κB (p65 and p50) and MAPK (ERK1/2, JNK, and p38) in a dose dependent manner. These results suggest that the anti-inflammatory activity of SG results from its modulation of pro-inflammatory cytokines and mediators via the suppression of NF-κB activation and MAPK phosphorylation.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzopyrans/pharmacology , Inflammation/drug therapy , Sargassum/chemistry , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/isolation & purification , Benzopyrans/administration & dosage , Benzopyrans/isolation & purification , Cell Line , Cytokines/metabolism , Dose-Response Relationship, Drug , Inflammation/pathology , Inflammation Mediators/metabolism , Lipopolysaccharides , Macrophages/drug effects , Macrophages/metabolism , Mice , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Phosphorylation/drug effects
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