• 제목/요약/키워드: Mitogen activated protein kinase

검색결과 793건 처리시간 0.036초

Fractionated Coptis chinensis Extract and Its Bioactive Component Suppress Propionibacterium acnes-Stimulated Inflammation in Human Keratinocytes

  • Lee, Jin Wook;Kang, Yoon Joong;Choi, Hyun Kyung;Yoon, Young Geol
    • Journal of Microbiology and Biotechnology
    • /
    • 제28권6호
    • /
    • pp.839-848
    • /
    • 2018
  • Coptis chinensis (CC) is widely used in Asian countries to treat inflammatory diseases. We investigated the anti-inflammatory activity of the aqueous fraction separated from CC extract and of berberine, its key bioactive component, in human keratinocytes and the possible molecular mechanisms underlying this. Treating HaCaT keratinocytic cells with heat-killed Propionibacterium acnes induced nitric oxide and proinflammatory cytokine (e.g., tumor necrosis $factor-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-8) production and their mRNA expression; these effects were suppressed by pretreatment with the aqueous fraction or berberine, which also suppressed the phosphorylation of ERK, JNK, and p38 kinases and the nuclear expression of nuclear factor $(NF)-{\kappa}B$ p65 in P. acnes-stimulated cells. Thus, the aqueous fraction and berberine effectively exerted anti-inflammatory activities by suppressing mitogen-activated protein kinase and $NF-{\kappa}B$ signaling pathways in human keratinocytes and may be used for treating P. acnes-induced inflammatory skin diseases.

Sequential administration of camptothecin sensitizes human colon cancer HCT116 cells to paclitaxel via $p21^{Cip1/WAF1}$

  • Yoo, Jung-Min;Kim, Yun-Jin;Lee, Sung-Jae;Kim, Sang-Hoon
    • Animal cells and systems
    • /
    • 제15권1호
    • /
    • pp.9-17
    • /
    • 2011
  • Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

Galangin and Kaempferol Suppress Phorbol-12-Myristate-13-Acetate-Induced Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma HT-1080 Cells

  • Choi, Yu Jung;Lee, Young Hun;Lee, Seung-Taek
    • Molecules and Cells
    • /
    • 제38권2호
    • /
    • pp.151-155
    • /
    • 2015
  • Matrix metalloproteinase (MMP)-9 degrades type IV collagen in the basement membrane and plays crucial roles in several pathological implications, including tumorigenesis and inflammation. In this study, we analyzed the effect of flavonols on MMP-9 expression in phorbol-12-myristate-13-acetate (PMA)-induced human fibrosarcoma HT-1080 cells. Galangin and kaempferol efficiently decreased MMP-9 secretion, whereas fisetin only weakly decreased its secretion. Galangin and kaempferol did not affect cell viability at concentrations up to $30{\mu}M$. Luciferase reporter assays showed that galangin and kaempferol decrease transcription of MMP-9 mRNA. Moreover, galangin and kaempferol strongly reduce $I{\kappa}B{\alpha}$ phosphorylation and significantly decrease JNK phosphorylation. These results indicate that galangin and kaempferol suppress PMA-induced MMP-9 expression by blocking activation of NF-${\kappa}B$ and AP-1. Therefore, these flavonols could be used as chemopreventive agents to lower the risk of diseases involving MMP-9.

연자육의 항우울 효과 및 프로티옴 분석을 통한 기전 연구 (Comparison of Nelumbinis Semen Extract with Hypericum Perforatum and Fluoxetine in Animal Model of Depression)

  • 이진우;홍무창;신민규;배현수
    • 동의생리병리학회지
    • /
    • 제20권4호
    • /
    • pp.830-843
    • /
    • 2006
  • Clinical evidence suggests that Nelumbinis Semen extracts have antidepressive properties and may offer an interesting alternative for the treatment of mood disorders. It was the aim of the present study to compare the effects of Nelumbinis Semen extracts with those of fluoxetine and hypericum perforatum extract in the rat forced swimming test (FST) and chronic mild stress (CMS), a model of depression. In the FST, p.o. administration of Nelumbinis Semen extracts (1 mg) induced a statistically significant reduction of immobility. The active behaviors in that test did not reflect decreased general activity because Nelumbinis Semen extracts failed to alter the locomotor activity of rats, measured in the open field test. Moreover Nelumbinis Semen extracts was superior to fluoxetine and hypericum perforatum extract in the incidence of sexual side-effects. These effects of Nelumbinis Semen extracts on the rat behavior is to be ascribed to increased Cytochrome c oxidase polypeptide Vla-liver, Mitogen-activated protein kinase 1 , Adenylosuccinate synthetase, and Aldehyde dehydrogenase in rat hippocampus.

좀보리사초의 IgE 매개성 알레르기 반응 억제 효과 및 기전 (Carex pumila Extract Supresses Mast Cell Activation and IgE-Mediated Allergic Response in Mice)

  • 임한나;김영미
    • 한국식품위생안전성학회지
    • /
    • 제29권4호
    • /
    • pp.356-362
    • /
    • 2014
  • Allergic diseases have increased rapidly over the past decades, affecting an estimated 20~30% of the population in developed countries. In this study, we investigated whether or not a typical costal sand dune plant Carex pumila (CPE) suppresses the activation of mast cells and IgE-mediated allergic response in vitro and in vivo. As the results, the extract of Carex pumila inhibited antigen-stimulated degranulation in RBL-2H3 cells and Bone marrow-derived mast cells (BMMCs), and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. CPE also suppressed the production of pro-inflammatory cytokines, TNF-${\alpha}$ and IL-4, in antigen-stimulated mast cells. As its mechanism of action, CPE inhibited the activation of Syk in $Fc{\varepsilon}RI$-mediated signalling pathway, and that of LAT, a downstream adaptor molecule of Syk, in a dose-dependent manner. CPE also suppressed the activation of mitogen-activated protein (MAP) kinases, p38, ERK1/2, JNK, and Akt. Altogether, CPE inhibited mast cell activation and IgE-mediated allergic response by antigen through suppressing the activation of Syk. These results suggest that CPE may be useful for the treatment of allergic diseases.

갯무 추출물의 스코폴라민 유도 기억력 저하 모델에서의 뇌신경 보호 효과 (Neuroprotective Effect of Wild Radish Extract on Scopolamine Induced Memory Impairment)

  • 허진영;최상윤;염미정
    • 한국식생활문화학회지
    • /
    • 제36권6호
    • /
    • pp.633-639
    • /
    • 2021
  • Raphanus sativus var. hortensis f. raphanistroides Makino (Korean wild radish [WR]) are root vegetables belonging to the Brassicaceae family. These radish species mostly grow in sea areas in Asia, where they have been traditionally used as a medicinal food to treat various diseases. To investigate the effect of WR on neuronal cell death in SH-SY5Y cells, beta-amyloid was used to develop the cell death model. WR attenuated neuronal cell death in SH-SY5Y and regulated the mitogen-activated protein kinase (MAPK) signaling. WR extract also inhibited acetylcholinesterase inhibitor activity. Additionally, the WR treatment group ameliorated the behavior of the memory-impaired mice in a scopolamine-induced mouse model. In the behavior test, WR treated mice showed shorter escape latency and swimming distance and improved the platform-crossing number and the swimming time within the target quadrant. Furthermore, WR prevented histological loss of neurons in hippocampal CA1 regions induced by scopolamine. This study shows that WR can prevent memory impairment which may be a crucial way for the prevention and treatment of memory dysfunction and neuronal cell death.

소장상피세포에 있어서 느릅나무 당단백질이 톨루엔에 의해 유도된 환경독성 기작에 미치는 효과 (Effects of a Glycoprotein Isolated from Ulmus davidiana Nakai on Toluene-Induced Ecotoxicity and its Mechanism in Human Intestinal Epithelial Cells)

  • 김도완;김지윤;박문기;이세중
    • 한국환경과학회지
    • /
    • 제28권2호
    • /
    • pp.249-257
    • /
    • 2019
  • Ulmus davidiana Nakai (UDN) has been traditionally used as a herbal medicine to treat inflammatory diseases in Korea. In the present study, we investigated the anti-ecotoxic potential of a 116 kDa glycoprotein isolated from UDN (UDN glycoprotein) in human intestinal epithelial INT-407 cells. We demonstrated that UDN glycoprotein ($20{\mu}g/mL$) could inhibit the production of lactate dehydrogenase (LDH) induced by toluene, an ecotoxic substance. Additionally, we found that the toluene-induced intestinal cytotoxicity was mediated by the phosphorylation of p38 Mitogen-Activated Protein Kinase (MAPK) via the production of intracellular Reactive Oxygen Species (ROS). The UDN glycoprotein significantly decreased the levels of ROS production and p38 MAPK activation in toluene-stimulated INT-407 cells. Moreover, the UDN glycoprotein inhibits the phosphorylation of nuclear factor-kappa B ($NF-{\kappa}B$), which is responsible for the production of LDH, in toluene-stimulated INT-407 cells. Collectively, our data indicate that UDN glycoprotein is a natural antioxidant and a modulator of ecotoxicity signaling pathways in human intestinal epithelial cells.

Noonan syndrome and RASopathies: Clinical features, diagnosis and management

  • Lee, Beom Hee;Yoo, Han-Wook
    • Journal of Genetic Medicine
    • /
    • 제16권1호
    • /
    • pp.1-9
    • /
    • 2019
  • Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40-50%), SOS1 (10-20%), RAF1 (3-17%), and RIT1 (5-9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.

Anti-inflammatory effect of Arctium minus on LPS-stimulated RAW 264.7 cells

  • Yang, Hye-Ji;Jang, Min-Hye;Kang, Yoon Joong
    • 한국자원식물학회:학술대회논문집
    • /
    • 한국자원식물학회 2019년도 춘계학술대회
    • /
    • pp.115-115
    • /
    • 2019
  • Arctium minus (AM), commonly known as lesser burdock, is a dried fruit (seed) of Aructium lappa L. that belong to Asteraceae. It has been used traditionally as herbal medicine because of its anti-inflammatory effects, and it has been applied to treat various diseases like allergies, skin aging, hyperlipidemia and urinary stone. In this study, we investigated the inhibitory effects of AM on the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Pre-treatment of the RAW 264.7 cells with AM considerably inhibited and reduced production of Nitric Oxide (NO) and pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and also shows suppression of nuclear factor-kappa B (NF-${\kappa}B$) translocation. In addition, AM treatment considerably reduced phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. Our results indicate that the AM has potential to inhibit inflammation through suppressing production of inflammatory mediators via both the NF-${\kappa}B$ and MAPK signaling pathway. We therefore suggest that AM might be effective therapeutics for the treatment of various inflammatory diseases.

  • PDF

Red Sea Cucumber (Stichopus japonicus) Suppresses Cancer Progression by Promoting the ROS-Me diated Inhibition of the MAPK Pathway

  • Kim, Jusnseong;Kim, Eun-A;Kang, Nalae;Choi, Youn Kyung;Heo, Soo-Jin
    • 한국해양바이오학회지
    • /
    • 제12권2호
    • /
    • pp.91-98
    • /
    • 2020
  • Stichopus japonicas (red sea cucumbers) inhabit the coastal sea surrounding Jeju Island, South Korea, and are thought to have various medicinal properties. In this study, we investigated the anticancer activity of a red sea cucumber (S. japonicus) collected from Jeju Island. We obtained the red sea cucumber extract (RSCE), and observed that it inhibited the tumor cell growth and increased reactive oxygen species (ROS) production associated with the induction of apoptosis through the mitogen-activated protein kinase (MAPK) pathway in murine colon carcinoma cells (CT-26). Treatment with RSCE and N-acetylcysteine, which is a ROS scavenger, increased ROS production and apoptosis via the regulation by the MAPK pathway on the ERK and JNK compared with the nontreated group. Therefore, RSCE promotes ROS-mediated suppression of the ERK and JNK activation, and subsequently inhibits cancer progression, suggesting that RSCE may be beneficial in treating colon carcinoma.