• Title/Summary/Keyword: JNK/c-Jun

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Anti-inflammatory effect of extract of Pulsatilla koreana $N_{AKAI}$ in LPS-stimulated Murine peritoneal macrophage (LPS 로 활성화된 복강 대식세포에서 백두옹 추출물의 항염증 효과)

  • Park, Sung-Joo;Song, Ho-Joon
    • The Korea Journal of Herbology
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    • v.22 no.1
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    • pp.111-117
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    • 2007
  • Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract from Pulsatilla koreana $N_{AKAI}$ (PK) on the peritoneal macrophage. Methods : To evaluate of anti-inflammatory of PK, we examined cytokines and NO production in lipopolysacchride (LPS)-induced macrophages. Furthermore, we examined molecular mechanism using western blot. Results : 1.Extract from PK reduced LPS-induced NO, tumor necrosis factor-a ($TNF-{\alpha}$), interleukin (IL)-6 and IL-12 production in peritoneal macrophages. 2.Extract from PK itself does not have any cytotoxic effect. PK inhibited the activation of extracelluar signal-regulated kinase(ERK 1/2) but not another mitogen-activated protein kinases (MAPKs) such as p38, c-Jun NH2-terminal kinase (JNK) and the degradation of inhibitory kappa B a ($I_{k}B_{a}$) does not any effect in the LPS-stimulated peritoneal macrophages. Conclusion : PK down-regulated LPS-induced NO and cytokines production, which may be provide a clinical basis for anti-inflammatory properties of PK.

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Gene Expression Profiling Reveals that Paeoniflorin Has an Apoptotic Potential in Human Leukemia U937 Cells

  • Lim, Soo-Hyun;Ahn, Kwang-Seok;Kim, Sung-Hoon;Jang, Hyeung-Jin
    • Molecular & Cellular Toxicology
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    • v.5 no.4
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    • pp.335-345
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    • 2009
  • A major source of paeoniflorin (PF) which was from the Paeonia lactiflora root, has been used as a herbal medicine in East Asia for its antiallergic, antiinflammatory, and immunoregulatory effects. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by PF using DNA microarrays and computational gene-expression analysis tools in human leukemia U937 cells. A comparative global transcription analysis between treatment with PF and anisomycin (AM) that induces apoptosis in U937 cells revealed that c-Jun-$NH_2$-kinase (JNK) pathway related genes were less expressed in PF-treated cells. Elucidation of the mechanisms by which PF conducts its anti-cancer activities through comparative analysis of the gene expression is necessary to provide a solid foundation for its use as a promising agent in prevention and treatment strategies.

Radiation-induced Cochlea Hair Cell Death: Mechanisms and Protection

  • Tan, Pei-Xin;Du, Sha-Sha;Ren, Chen;Yao, Qi-Wei;Yuan, Ya-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5631-5635
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    • 2013
  • Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini-review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC), are claimed to be effective at reducing radiation-inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre-examined in order to minimize the damage to cochlea hair cells.

Water Extract of Flowers of Magnolia Denudata Inhibits LPS-induced Nitric Oxide and Pro-inflammatory Cytokines Production in Murine Peritoneal Macrophage by Inhibiting $NF-{\kappa}B$ Activation (LPS로 활성화된 복강 대식세포에서 신이 추출물의 염증성 사이토카인 및 NO 억제 효과)

  • Kim, Do-Yun;Jeong, Won-Seok;Moon, Hyoung-Chul;Park, Sung-Joo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.916-920
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    • 2007
  • Flowers of Magnolia denudata has been reported to possess a variety of pharmacological activities. In this study, we investigated the anti-inflammatory effects and mechanism of the water extract of Flowers of Magnolia denudata(MD) in lipopolysacchride (LPS)-mediated inflammatory mediators in murine peritoneal macrophages. MD itself does not have any toxic effects in murine peritoneal macrophages. MD inhibits LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, IL-6 and IL-12 production in murine peritoneal macrophages. Furthermore, we have found that MD inhibited LPS-induced $NF-{\kappa}B$ but not c-Jun N-terminal kinase (JNK), p38 and extracellular signal-ragulated kinase (ERK) activation. These results suggested that MD inhibit LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-12 via suppression of the $NF-{\kappa}B$ activation.

Immunostimulatory effect of Korean traditional medicine Acanthopanacis Cortex

  • Chang, In-Ae;Shin, Hye-Young;Kim, Youn-Chul;Yun, Yong-Gab;Park, Hyun
    • Natural Product Sciences
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    • v.13 no.4
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    • pp.283-288
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    • 2007
  • Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.

Effect of nitric oxide on the expression of matrix metalloproteinases by the UV irradiated human dermal fibroblasts

  • Taeboo Choe;Lee, Bumchun;Park, Inchul;Seokil Hong
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.28 no.1
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    • pp.31-41
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    • 2002
  • The production of matrix matalloproteinases(MMPs) by the UV irradiated skin fibroblast and the degradation of extracellular matrix(ECM) by these enzymes is known as one of the main reasons of photoaging. Recently, Fisher group showed that the MMP expression is mainly regulated by the mitogen-activated protein(MAP) kinas family, such as extracellular signal-regulated kinase(ERK), c-Jun amino-terminal kinase(JNK) and p38, each of which forms a signaling pathway. In this work we first examined the effect of nitric oxide (NO) on the production of MMP-1 and MMP-2 by the human dermal fibroblasts (HDFs). NO is a multifunctional messenger molecule generated from L-arginine and involved in many kinds of signaling pathway. We found that the treatment of HDF with NO donor, sodium nitroprusside (SNP) enhanced the expression of MMPs with or without UV irradiation and the treatment with nitric oxide synthase (NOS) inhibitors resulted in the significant decrease of MMPs production. From these results, we concluded that the production of MMPs by the UV irradiated HDF is regulated through the signaling pathway involving NO and cyclic GMP.

Studies on Skin Anti-aging Effect of Chungpyesagan-tang(CPSGT) (청폐사간탕(淸肺瀉肝湯)의 피부 항노화 효과에 대한 연구)

  • Bo-Hee, Jeon;Young-Chae, Song;Hee-Taek, Kim;Yong-Min, Kim
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.36 no.1
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    • pp.40-49
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    • 2023
  • Objectives : This study was conducted to confirm the skin anti-aging effect of Chungpyesagan-tang(CPSGT) extract. Methods : We performed MMT assay to confirm the cytotoxicity of CPSGT. After inducing matrix metalloproteinase-1(MMP-1) with tumor necrosis factor-α(TNF-α), we investigated mRNA expression and protein secretion of MMP-1 by real-time RT-PCR and ELISA. In addition, we measured the protein expression of mitogen-activated protein kinases(MAPKs) and transcription factors by western blot. Results : CPSGT was not cytotoxic at 25-800㎍/㎖. The mRNA expression and protein secretion of MMP-1 decreased when treated with CPSGT. The protein expression of p-ERK, p-JNK, p-p38 was decreased by CPSGT. In addition, the protein expression of p-c-jun and p-NF-κB, which are transcription factors, were also decreased. Conclusion : This suggests that CPSGT can inhibit MMP-1 and thus be a potential anti-aging substance.

Therapeutic effect of Shinkiwhan, herbal medicine, regulates OPG/RANKL/RANK system on ovariectomy-induced bone loss rat

  • Seo, Il-bok;Lee, Kang Pa;Park, Sun-young;Ahn, Sang-hyun
    • Korean Journal of Exercise Nutrition
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    • v.24 no.3
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    • pp.19-24
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    • 2020
  • [Purpose] Although physical activity is required to prevent or ameliorate osteoporosis, medicine prescription should precede it, since it may be limited in severe osteoporosis patients. Furthermore, osteoporosis has a great effect on physical activity disorders that accompany fractures and pain, and therefore, research on treatment or prevention to decrease the number of patients is required. The purpose of this study was to discover candidate substances from natural products with an effective pharmacological action and to prepare basic data to help patients. [Methods] To prepare the osteoporosis model, ovariectomy (OVX) was performed using surgical methods. The prepared prescription [Shinkiwhan (SKH), a Korean medicine] was administered orally at a dose of 210 mg/kg/day for 8 weeks. After completion of the animal experiment, the bone mineral density (BMD) was analyzed using double-energy X-ray absorptiometry. The analysis of the effect of drugs on bones was performed using histological analysis and immunostaining. [Results] SKH increased the BMD in the OVX rats. Furthermore, SKH significantly increased the expression of osteoprotegerin and downregulated receptor activator of nuclear factor kappa B ligand and phosphorylation of c-jun N-terminal kinases in the bones of the OVX model. [Conclusion] Our findings suggest a protective effect of SKH against BMD loss in the OVX model.

Immunostimulatory Activity of Hibiscus syriacus L. Leaves in Mouse Macrophages, RAW264.7 cells, and Immunosuppressed Mice

  • Na Gyeong Geum;Ju Hyeong Yu;So Jung Park;Min Yeong Choi;Jae Won Lee;Gwang Hun Park;Hae-Yun Kwon;Jin Boo Jeong
    • Korean Journal of Plant Resources
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    • v.35 no.6
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    • pp.697-703
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    • 2022
  • Under the COVID-19 pandemic, interest in immune enhancement is increasing. Although the immune-enhancing activity of plants of the genus Hibiscus has been reported, there is no study on the immune-enhancing activity of H. syriacus. Thus, in this study, we investigated the immune-enhancing activity of Hibiscus syriacus leaves (HSL) in mouse macrophages, RAW264.7 cells, and immunosuppressed mice. HSL increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) and activated the phagocytosis in RAW264.7 cells. The HSL-mediated production of immunostimulatory factors was dependent on toll-like receptor 4 (TLR4), p38, and c-Jun N-terminal kinase (JNK) in RAW264.7 cells. In the immunosuppressed mouse model, HSL increased the spleen index, the levels of the cytokines, and the numbers of lymphocytes, neutrophils, and monocytes. Taken together, HSL may be considered to have immune-enhancing activity and be expected to be used as a potential immune-enhancing agent.

Immune enhancing activity of Sargassum horneri extracts via MAPK pathway in macrophages (대식세포에서 괭생이모자반 추출물의 MAPKs 기전 통한 면역활성 증가 효과)

  • 김동섭;김민지;성낙윤;한인준;김건;김춘성;유영춘;정윤우
    • Journal of Marine Bioscience and Biotechnology
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    • v.15 no.1
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    • pp.12-23
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    • 2023
  • Sargassum horneri (SH), a brown macroalgae, has medicinal properties. The present study investigated the immune-enhancing effects of SH extract on peritoneal macrophages (PM). The SH significantly increased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in PM. It was confirmed that SH significantly increased NO expression through the increase of iNOS protein expression, which is the up-regulation pathway. Additionally, it was determined if SH activates the mitogen-activated protein kinase (MAPK) pathway, an upper regulatory mechanism that influences TNF-α, IL-6, and NO expression. Consequently, SH significantly increased the phosphorylation of p38, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK), all of which are MAPK pathway proteins. Moreover, the immune-enhancing effects of SH on another macrophage cell line, bone marrow-derived macrophages were investigated. It was observed that SH significantly enhanced TNF-α, IL-6, and NO production. Overall, this study demonstrates the immune-enhancing effects of SH on macrophages via activated MAPK pathway. Therefore, it suggests that SH has the potential to improve immunological activity in various macrophage cell lines and can be useful as an immune-enhancing treatment.