• Title/Summary/Keyword: Protein kinases

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Effects of Patrinia Scabiosaefolia Aqueous Extract on Cytokine and NF-κB Activation in LPS-induced RAW 264.7 Cells and Mouse (패장(敗醬) 물 추출물의 LPS로 유도된 RAW 264.7 세포와 mouse 염증모델에서 cytokine 및 NF-κB의 활성에 미치는 효과)

  • Ryu, Ik-Han;Cho, Hae-Joong;Song, Mi-Hwa;Choi, Chang-Min
    • The Journal of Korean Obstetrics and Gynecology
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    • v.30 no.2
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    • pp.1-15
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    • 2017
  • Objectives: The object of this study was to identify the anti-inflammatory effects of Patrinia scabiosaefolia aqueous extract (PSE). Methods: RAW 264.7 cells were pre-treated with PSE and then incubated with or without lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), secretion of pro-inflammatory cytokine, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-${\kappa}B$) were measured. In addition, we observed mice survival rate after LPS and their cytokine levels of serum. We also observed inflammatory and hemorrhagic change on the histological sections of the liver. Results: PSE inhibited LPS-induced NO production, interleukin (IL)-6 secretion, c-Jun NH2-terminal kinase (JNK) and NF-${\kappa}B$ activation. In addition, PSE reduced the death rate of LPS-induced mice and IL-6 production on the serum of mice. PSE inhibited inflammation and hemorrhage on liver tissue as well. Conclusions: The results suggest that PSE have anti-inflammatory effects by inhibited NF-${\kappa}B$ and JNK activation, IL-6 secretion, and NO production. So PSE may be effective treatment for the inflammatory disease.

Anti-inflammatory Effects of Flavokavain C from Kava (Piper methysticum) Root in the LPS-induced Macrophages (LPS로 유도된 대식세포에서 카바뿌리로부터 분리한 Flavokavain C의 항염증 효과)

  • Park, Chung;Han, Jong-Min
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.311-320
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    • 2016
  • Kava (Piper methysticum, P. methysticum) is used as traditional herbal medicine for urogenital diseases, rheumatisms, gastrointestinal problems, respiratory irritations, and pulmonary pains. We identified a flavokavain C (FKC) from P. methysticum, which showed anti-inflammatory activity on nuclear factor ${\kappa}B$ (NF-${\kappa}B$)-dependent nitric oxide (NO) production and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. FKC inhibited accumulation of reactive oxygen species (ROS), such as hydrogen peroxide, and was able to dose-dependently reduce the LPS-induced NO production and the expression of various inflammation-associated genes (iNOS, IL-$1{\beta}$, IL-6) through inhibition of NF-${\kappa}B$ and MAPKs (ERK and JNK). In conclusion, these results indicate that FKC may have the potential to prevent inflammation process including NF-${\kappa}B$ and MAPKs pathways, and it could be applicable to functional cosmetics for anti-inflammation and antioxidant properties.

Increased calcium-mediated cerebral processes after peripheral injury: possible role of the brain in complex regional pain syndrome

  • Nahm, Francis Sahngun;Lee, Jae-Sung;Lee, Pyung-Bok;Choi, Eunjoo;Han, Woong Ki;Nahm, Sang-Soep
    • The Korean Journal of Pain
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    • v.33 no.2
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    • pp.131-137
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    • 2020
  • Background: Among various diseases that accompany pain, complex regional pain syndrome (CRPS) is one of the most frustrating for patients and physicians. Recently, many studies have shown functional and anatomical abnormalities in the brains of patients with CRPS. The calcium-related signaling pathway is important in various physiologic processes via calmodulin (CaM) and calcium-calmodulin kinase 2 (CaMK2). To investigate the cerebral mechanism of CRPS, we measured changes in CaM and CaMK2 expression in the cerebrum in CRPS animal models. Methods: The chronic post-ischemia pain model was employed for CRPS model generation. After generation of the animal models, the animals were categorized into three groups based on changes in the withdrawal threshold for the affected limb: CRPS-positive (P), CRPS-negative (N), and control (C) groups. Western blot analysis was performed to measure CaM and CaMK2 expression in the rat cerebrum. Results: Animals with a decreased withdrawal threshold (group P) showed a significant increment in cerebral CaM and CaMK2 expression (P = 0.013 and P = 0.021, respectively). However, groups N and C showed no difference in CaM and CaMK2 expression. Conclusions: The calcium-mediated cerebral process occurs after peripheral injury in CRPS, and there can be a relationship between the cerebrum and the pathogenesis of CRPS.

The anti-inflammatory effect of Achyranthes japonica on lipopolysaccharide-induced inflammatory activity in murine macrophages (LPS로 유도한 대식세포의 염증반응에서 우슬의 항염증 효과)

  • Kim, Min-Sun;Jeong, Jin-Soo;Lee, Hye-Youn;Ju, Young-Sung;Bae, Gi-Sang;Seo, Sang-Wan;Cho, Il-Joo;Park, Sung-Joo;Song, Ho-Joon
    • The Korea Journal of Herbology
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    • v.26 no.2
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    • pp.51-57
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    • 2011
  • Objectives : Achyranthes japonica (AJ) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that AJ could show the anti-inflammatory effects in macrophages. In this experiment, we studied whether AJ could inhibit the inflammatory responses in macrophages. Methods : To measure out the cytotoxicity of AJ, we performed the MTT assay. We evaluated the nitric oxide (NO) production, and cytokine production such as interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF)-a. We also investigated the cellular mechanims such as mitogen activated protein kinases (MAPK)s and nuclear factor kappa B (NF-kB). Results : AJ inhibited lipopolysaccharide (LPS)-induced NO production. AJ also inhibited production levels of IL-1b, IL-6 and TNF-a in LPS-stimulated macrophage. Finally, western blot analysis showed that AJ treatment inhibited the activation of p38 but not of extracellular signal-regulated kinase, c-jun NH2-terminal kinase and NF-kB. Conclusions : These results showed that AJ down-regulated the inflammatory response via p38 in macrophages, which suggest that AJ could be a candidate on treating inflammatory diseases.

Inhibition of Gap Junctional Intercellular Communication in Rat Liver Epithelial Cells Induced by BHT and Propyl Gallate (간상피세포에서 BHT와 propyl gallate에 의한 gap junctional intercellular communication 억제 효과)

  • Kim, Ji-Sun;Kim, Sung-Ran;Ahn, Ji-Yun;Ha, Tae-Youl;Kang, Kyoung-Sun;Kim, Sun-A
    • Korean Journal of Food Science and Technology
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    • v.39 no.5
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    • pp.558-563
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    • 2007
  • This study was conducted to analyze the cytotoxic effects of butylated hydroxytoluene (BHT) and propyl gallate (PG) in WB-F344 rat liver epithelial cells. Here we measured the inhibition level of gap junctional intercellular communication (GJIC) and elucidated the relationships between GJIC and mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. The cytotoxicities of BHT and PG appeared at concentrations of 1.0mM and 0.25mM, respectively, in the WB-F344 cells; and GJIC inhibition, which was analyzed by a scrape-loading/dye transfer assay and Western blotting analysis, appeared at 0.6mM for BHT and 0.1mM for PG, respectively. Also, the phosphorylations of Cx43, ERK, JNK, and p38 increased in dose-dependent manners. This suggests that BHT and PG treatments inhibited GJIC by the phosphorylation of MAPKs prior to cell damage.

Anti-inflammatory Effects of the Methanol Extracts of Phlox subulata on LPS-induced RAW264.7 Macrophages and BV2 Microglia (꽃잔디 메탄올 추출물의 RAW264.7 대식세포와 BV2 미세아교세포에서의 항염증 효과)

  • Kim, Kwan-Woo;Li, Jing;Lee, Hwan;Lee, Dong-Sung;Oh, Hyuncheol;Kim, Youn-Chul
    • Korean Journal of Pharmacognosy
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    • v.50 no.4
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    • pp.291-298
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    • 2019
  • Phlox subulata is a perennial herbaceous flower and is a member of the Polemoniaceae family. This plant is known to resist to various stresses including salt, drought, heat, and cold stresses. In this investigation, we evaluated the ant-inflammatory effect of the methanolic extract of P.subulata(PSM) on lipopolysaccharide(LPS)-induced RAW264.7 macrophages and BV2 microglia. PSM reduced the production of nitric oxide(NO) in LPS-stimulated both RAW264.7 and BV2 cells, but did not affect to the production of prostaglandin E2(PGE2). It inhibited the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 in both cells. In addition, PSM suppressed the production of pro-inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by PSM. Thus, these results suggested that P.subulata can be a candidate material to treat inflammatory diseases.

The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

  • Kwon, Seung-Hwan;Ma, Shi-Xun;Hwang, Ji-Young;Ko, Yong-Hyun;Seo, Ji-Yeon;Lee, Bo-Ram;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.268-282
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    • 2016
  • In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

Berberine Chloride Inhibits Receptor Activator of $NF-{\kappa}B$ Ligand-induced Osteoclastogenesis via Preventing ERK Activation

  • Cheon, Myeong-Sook;Kim, Myung-Hee;Lee, Su-Ui;Ryu, Shi-Yong;Kim, Ho-Kyoung;Min, Yong-Ki;Kim, Seong-Hwan
    • Korean Journal of Oriental Medicine
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    • v.13 no.2 s.20
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    • pp.157-164
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    • 2007
  • An imbalance in bone remodeling that is caused by increased bone resorption over bone formation leads to most adult skeletal diseases including osteoporosis. Since the development of anti-resorptive agents from natural substances has recently gained more interest in the treatment of osteoporosis, we evaluated the effects of 222 natural compounds on receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced of tartrate-resistance acid phosphatase (TRAP) activity in RAW264.7 murine macrophage cell, and found that berberine chloride is one of compounds inhibiting RANKL-induced TRAP activity. Berberine chloride significantly inhibited the RANKL-induced TRAP activity and the formation of multinucleated osteoclasts in a dose-dependent manner. In addition, berberine chloride prevented the RANKL-induced mRNA expression of TRAP, matrix metalloproteinase 9 and c-Src, which have been known to be highly expressed in the process of osteoclastogenesis. Interestingly, berberine chloride prevented the RANKL-induced activation of extracellular signal-regulated kinase (ERK) which is one of mitogen-activated protein (MAP) kinases. In conclusion, berberine chloride could inhibit the osteoclastogenesis via preventing the activation of ERK/MAP kinase signaling pathway.

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Fucoidan Induces Apoptosis in A2058 Cells through ROS-exposed Activation of MAPKs Signaling Pathway

  • Ryu, Yea Seong;Hyun, Jin Won;Chung, Ha Sook
    • Natural Product Sciences
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    • v.26 no.3
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    • pp.191-199
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    • 2020
  • Fucoidan, a natural component of brown seaweed, has various biological activities such as anti-cancer activity, anti-oxidant, and anti-inflammatory against various cancer cells. However, the fucoidan has been implicated in melanoma cells via apoptosis signaling pathway. Therefore, we investigated apoptosis with fucoidan in A2058 human melanoma cells with dose- and time-dependent manners. In our results, A2058 cells viability decreased at relatively short-time and low-concentration through fucoidan. This effects of fucoidan on A2058 cells appeared to be mediated by the induction of apoptosis, as manifested by morphological changes through DNA-binding dye Hoechst 33342 staining. When a dose of 80 ㎍/mL fucoidan was treated, the cells were observed: crescent or ring-like structure, chromatin condensation, and nuclear fragmentation. With the increase at 100 ㎍/mL fucoidan, the cell membrane is intact throughout the total process, including membrane blebbing and loss of membrane integrity as well as increase of sub-G1 DNA. Furthermore, to understand the exact mechanism of fucoidan-treated in A2058 cells, western blotting was performed to detect apoptosis-related protein expression. In this study, Bcl-2 family proteins can be regulated by fucoidan, suggesting that fucoidan-induced apoptosis is modulated by intrinsic pathway. Therefore, expression of Bcl-2 and Bax may result in altered permeability, activating caspase-3 and caspase-9. And the cleaved form of poly ADP-ribose polymerase was detected in fucoidan-treated A2058 cells. These results suggest that A2058 cells are highly sensitive to growth inhibition by fucoidan via apoptosis, as evidenced by activation of extracellular signal-regulated kinases/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.

The protective effect of berberine on Propionibacterium acnes-induced inflammatory response in human monocytes (여드름균에 의해 염증 반응이 유도된 인간 단핵구 세포에서 알칼로이드 화합물 berberine의 항염증 효과)

  • Kim, Hyun Pyo;Yoon, Young Geol
    • Journal of Applied Biological Chemistry
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    • v.61 no.2
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    • pp.181-186
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    • 2018
  • In this study, we investigated the anti-inflammatory activity of berberine using human monocytes. Infection of Propionibacterium acnes induced the production of nitric oxide (NO) and the pro-inflammatory cytokines such as, $TNF-{\alpha}$, IL-8 and $IL-1{\beta}$ in THP-1 monocytic cells. However, when berberine was supplemented in these P. acnes-induced THP-1 cells, the production of pro-inflammatory cytokines and NO was significantly reduced. We also analyzed signaling pathways of the antiinflammatory function of berberine and found that berberine suppressed the phosphorylation of ERK1/2, JNK and p38 and the expression and nuclear translocation of $NF-{\kappa}B$ p65 in the P. acnes-induced cells. From these results, we concluded that berberine can effectively exert the anti-inflammatory activity via suppressing the $NF-{\kappa}B$ and mitogen-activated protein kinases signaling pathways in human monocytes. Moreover, these results suggest the feasibility of developing natural therapeutics using berberine for the treatment of P. acnes-induced inflammatory diseases.