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Pesquisa : B01.650.940.800.575.912.250.150.501 [Categoria DeCS]
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[PMID]:28684144
[Au] Autor:Li MY; Mi C; Wang KS; Wang Z; Zuo HX; Piao LX; Xu GH; Li X; Ma J; Jin X
[Ad] Endereço:Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
[Ti] Título:Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling.
[So] Source:Chem Biol Interact;274:58-67, 2017 Aug 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Hypoxia enhances the development of solid tumors. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor of tumor regulation. HIF-1α regulates several target genes involved in many aspects of cancer progression, including angiogenesis, metastasis, and cell proliferation, as well as imparting resistance to cancer treatment. In this study, we assessed shikonin, which derives from the traditional medical herb Lithospermum erythrorhizon, for its anti-cancer effects in hypoxia-induced human colon cancer cell lines. Shikonin showed potent inhibitory activity against hypoxia-induced HIF-1α activation in various human cancer cell lines and efficient scavenging activity of hypoxia-induced reactive oxygen species in tumor cells. Further analysis revealed that shikonin inhibited HIF-1α protein synthesis without affecting the expression of HIF-1α mRNA or degrading HIF-1α protein. It was subsequently shown to attenuate the activation of downstream mTOR/p70S6K/4E-BP1/eIF4E kinase. Shikonin also dose-dependently caused the cell cycle arrest of activated HCT116 cells and inhibited the proliferation of HCT116 and SW620 cells. Moreover, it significantly inhibited tumor growth in a xenograft modal. These findings suggest that shikonin could be considered for use as a potential drug in human colon cancer therapy.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/toxicidade
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Naftoquinonas/toxicidade
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Fitogênicos/química
Antineoplásicos Fitogênicos/isolamento & purificação
Antineoplásicos Fitogênicos/uso terapêutico
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Células HCT116
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Lithospermum/química
Lithospermum/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Naftoquinonas/química
Naftoquinonas/isolamento & purificação
Naftoquinonas/uso terapêutico
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Transplante Heterólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Naphthoquinones); 0 (Reactive Oxygen Species); 3IK6592UBW (shikonin); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE


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[PMID]:28254482
[Au] Autor:Yen CY; Chiang WD; Liu SY; Wang KT; Liao EC; Hsieh CL
[Ad] Endereço:Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Dermatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Electronic address: vernayen@yahoo.com.tw.
[Ti] Título:Lithospermum erythrorhizon extract inhibits Der p2-induced inflammatory response through alleviation of thymic stromal lymphopoietin, nuclear factor Kappa B, and inflammasome expression in human bronchial epithelial cells.
[So] Source:J Ethnopharmacol;201:1-8, 2017 Apr 06.
[Is] ISSN:1872-7573
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:ETHNOPHARMACOLOGICAL RELEVANCE: Lithospermum erythrorhizon (LE) and Angelica sinensis (AS), widely used in several folk medicine for wound, pus discharge and dermatitis for the history of several hundred years in Asian countries. AIM OF STUDY: To investigate the therapeutic effect of LE and AS on Der p2-induced inflammatory response in human bronchial epithelial (BEAS-2B) cells. METHODS: The effects of Der p2 stimulation on thymic stromal lymphopoietin (TSLP), the nuclear factor kappa B (NF-κB) pathway, the inflammasome (specifically, the apoptosis speck-like protein [ASC] and nod-like receptor 3 [NLRP3]), Caspase-1 and the signal transducer and activator of transcription (STAT) 3 pathway were evaluated in the human bronchial epithelial (BEAS-2B) cells. RESULTS: The results indicated that LE, AS, and LE+AS reduced TSLP, I kappa B kinase-α, and NLRP3 levels; LE and AS reduced Caspase-1; LE and LE+AS also reduced NF-κB p50, NF-κB p65, ASC, and STAT3 levels. CONCLUSION: Both LE and AS aqueous extracts exert anti-inflammatory effects in Der p2-stimulated BEAS-2B cells. These effects may involve multiple mechanisms, including the inhibition of TSLP production as well as the suppression of IKKα, Caspase-1 and NLRP3; however, additional studies are warranted to elucidate the underlying mechanisms.
[Mh] Termos MeSH primário: Angelica
Anti-Inflamatórios/farmacologia
Células Epiteliais/efeitos dos fármacos
Lithospermum
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: Alérgenos
Antígenos de Dermatophagoides
Proteínas de Artrópodes
Brônquios/citologia
Proteínas Adaptadoras de Sinalização CARD
Caspase 1/metabolismo
Linhagem Celular
Citocinas/metabolismo
Proteínas do Citoesqueleto/metabolismo
Células Epiteliais/metabolismo
Seres Humanos
Inflamassomos/metabolismo
NF-kappa B/metabolismo
Fator de Transcrição STAT3/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Anti-Inflammatory Agents); 0 (Antigens, Dermatophagoides); 0 (Arthropod Proteins); 0 (CARD Signaling Adaptor Proteins); 0 (Cytokines); 0 (Cytoskeletal Proteins); 0 (Dermatophagoides pteronyssinus antigen p 2); 0 (Inflammasomes); 0 (NF-kappa B); 0 (PYCARD protein, human); 0 (Plant Extracts); 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (thymic stromal lymphopoietin); EC 3.4.22.36 (Caspase 1)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE


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[PMID]:28070931
[Au] Autor:Yoon JJ; Sohn EJ; Kim JH; Seo JW; Kim SH
[Ad] Endereço:College of Korean Medicine, Kyung Hee University, 1 Hoegidong, Dongdaemungu, Seoul, 131-701, Korea.
[Ti] Título:Anti-rheumatoid Arthritis Effect of Kaejadan via Analgesic and Antiinflammatory Activity in vivo and in vitro.
[So] Source:Phytother Res;31(3):418-424, 2017 Mar.
[Is] ISSN:1099-1573
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although Kaejadan (KJD), an herbal cocktail of three medicinal plants (Lithospermum erythrorhizon, Cinnamomum loureirii, and Salvia miltiorrhiza), has been traditionally used for the treatment of rheumatoid arthritis, its scientific evidence is not fully understood. Hence, we investigated antiinflammatory and analgesic mechanism of KJD in vivo and in vitro. Kaejadan suppressed the number of writhing responses in mice treated by acetic acid and showed antinociceptive effect by tail-flick test. Kaejadan abrogated serotonin or carrageenan or Freund's complete adjuvant (FCA)-induced paw edema and also reduced the level of Evans Blue for vascular permeability. Furthermore, KJD effectively reduced the positive responses for C-reactive protein and rheumatoid arthritis test in FCA-treated rats. Of note, KJD inhibited the level of lipid peroxide malondialdehyde and enhanced the level of superoxide dismutase in the hepatic tissues of FCA-treated rats. Additionally, KJD abrogated the levels of IL-1ß and IL-6 in lipopolysaccharide and IFN-γ-exposed RAW 264.7 cells. Also, KJD reduced the expression of cyclooxygenase 2 or inducible nitric oxide synthase at protein and mRNA levels in IFN-γ and lipopolysaccharide-exposed RAW 264.7 cells. Overall, our findings demonstrate that KJD exerts antiinflammatory and analgesic effects via enhancement of antioxidant activity and inhibition of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Analgésicos/farmacologia
Anti-Inflamatórios/farmacologia
Artrite Reumatoide/prevenção & controle
Cinnamomum/química
Medicamentos de Ervas Chinesas/farmacologia
Lithospermum/química
Extratos Vegetais/farmacologia
Salvia miltiorrhiza/química
[Mh] Termos MeSH secundário: Analgésicos/uso terapêutico
Animais
Anti-Inflamatórios/uso terapêutico
Artrite Reumatoide/tratamento farmacológico
Artrite Reumatoide/metabolismo
Proteína C-Reativa/metabolismo
Células Cultivadas
Medicamentos de Ervas Chinesas/uso terapêutico
Edema/tratamento farmacológico
Inflamação/tratamento farmacológico
Masculino
Camundongos
Camundongos Endogâmicos ICR
Extratos Vegetais/uso terapêutico
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics); 0 (Anti-Inflammatory Agents); 0 (Drugs, Chinese Herbal); 0 (Plant Extracts); 0 (kaejadan); 9007-41-4 (C-Reactive Protein)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE
[do] DOI:10.1002/ptr.5763


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[PMID]:27725239
[Au] Autor:Park JY; Kwak JH; Kang KS; Jung EB; Lee DS; Lee S; Jung Y; Kim KH; Hwang GS; Lee HL; Yamabe N; Kim SN
[Ad] Endereço:College of Korean Medicine, Gachon University, Seongnam 461-701, Republic of Korea. Electronic address: rhemf@hanmail.net.
[Ti] Título:Wound healing effects of deoxyshikonin isolated from Jawoongo: In vitro and in vivo studies.
[So] Source:J Ethnopharmacol;199:128-137, 2017 Mar 06.
[Is] ISSN:1872-7573
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:ETHNOPHARMACOLOGICAL RELEVANCE: Jawoongo is a traditional drug ointment (with a traditional botanic formula) used for the treatment of burns and wounds in Korea. One of the components of Jawoongo is Lithospermi Radix (LR, the dried root of Lithospermum erythrorhizon Siebold & Zucc., also known as Zicao or Gromwell), which contains deoxyshikonin and its derivatives. OBJECTIVE: The aim of the present study was to investigate the effects of deoxyshikonin on wound healing. MATERIALS AND METHODS: The effects of LR extract and deoxyshikonin on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVEC) and HaCaT cells, respectively. We evaluated protein expression of mitogen-activated protein kinase (MAPK) activation by Western blotting. The wound healing effects of deoxyshikonin was assessed in a mouse model of cutaneous wounds. RESULTS: The results showed that deoxyshikonin enhanced tube formation in HUVEC and migration in HaCaT cells. From the western blot analysis, we found that deoxyshikonin stimulated the phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in HaCaT cells. Moreover, 20µm deoxyshikonin-treated groups showed accelerated wound closure compared with the controls in a mouse model of cutaneous wounds. CONCLUSION: In conclusion, the current data indicate that deoxyshikonin treatment elevated tube formation in HUVECs, and that deoxyshikonin-induced proliferation and migration in HaCaT cells were mediated by the activation of ERK and p38 MAPKs, respectively. Collectively, these data suggest that deoxyshikonin in Jawoongo must be an active compound for may be wound healing.
[Mh] Termos MeSH primário: Lithospermum
Naftoquinonas/farmacologia
Extratos Vegetais/farmacologia
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Transformada
Movimento Celular/efeitos dos fármacos
Movimento Celular/fisiologia
Relação Dose-Resposta a Droga
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Células Endoteliais da Veia Umbilical Humana/fisiologia
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos ICR
Naftoquinonas/isolamento & purificação
Extratos Vegetais/isolamento & purificação
Distribuição Aleatória
Cicatrização/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Naphthoquinones); 0 (Plant Extracts); 43043-74-9 (deoxyshikonin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161012
[St] Status:MEDLINE


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[PMID]:27782842
[Au] Autor:Cho ES; Yi JM; Park JS; Lee YJ; Lim CJ; Bang OS; Kim NS
[Ad] Endereço:KM-Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea.
[Ti] Título:Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models.
[So] Source:BMC Complement Altern Med;16(1):419, 2016 Oct 26.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Oxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients. Until now, no effective preventive or therapeutic drug has been developed; therefore, the dose-limiting factor of OXIPN is still an obstacle in the use of oxaliplatin to treat cancer patients. In the present study, we report for the first time that the aqueous extract of Lithospermi radix (WLR) can attenuate the OXIPN in both in vitro and in vivo neuropathic models. METHODS: The protective effect of WLR on OXIPN was evaluated in vitro by quantifying nerve growth factor (NGF)-stimulated neurite outgrowth in PC12 cells treated with a combination of oxaliplatin and WLR. The neuroprotective potential of WLR was further confirmed by measuring the changes in nociceptive sensitivities to external mechanical stimuli in neuropathic animals induced by oxaliplatin. Histological and immunohistochemical studies were further done to examine the effect of WLR in mouse spinal cords and footpads. RESULTS: Oxaliplatin-induced neurotoxicity in NGF-stimulated PC12 cells. It could reduce the lengths and branching numbers of neuritis in NGF-stimulated PC12 cells. Co-treatment of WLR rescued the differentiated PC12 cells from the neurotoxicity of oxaliplatin. In a chronic OXIPN animal model, administration of oxaliplatin i.p. induced enhanced nociceptive sensitivity to mechanical stimuli (25.0 to 72.5 % of response rate) along with spinal activation of microglias and astrocytes and loss of intraepidermal nerve fibers in footpads, which is remarkably suppressed by oral administration of WLR (67.5 to 35 % of response rate at the end of experiment). Cytotoxicity of oxaliplatin determined in human cancer cells was not affected irrespective of the presence of WLR. CONCLUSIONS: In conclusion, we demonstrated that WLR can attenuate OXIPN in both in vitro and in vivo experimental models, which may be in part attributed to its anti-inflammatory activity in the spinal cord and its neuroprotective potential in the peripheral nerve system without affecting the anti-tumor potential of oxaliplatin. Therefore, WLR could be considered as a good starting material to develop a novel therapeutic agent targeting OXIPN. However, further studies should be done to elucidate the underlying mechanism such as molecular targets and active constituent(s) in WLR with neuroprotective potential.
[Mh] Termos MeSH primário: Lithospermum/química
Síndromes Neurotóxicas/tratamento farmacológico
Compostos Organoplatínicos/toxicidade
Doenças do Sistema Nervoso Periférico
Extratos Vegetais/farmacologia
Substâncias Protetoras/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Gânglios Espinais/efeitos dos fármacos
Seres Humanos
Imuno-Histoquímica
Masculino
Camundongos Endogâmicos C57BL
Fibras Nervosas/efeitos dos fármacos
Células PC12
Doenças do Sistema Nervoso Periférico/induzido quimicamente
Doenças do Sistema Nervoso Periférico/tratamento farmacológico
Extratos Vegetais/química
Substâncias Protetoras/química
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organoplatinum Compounds); 0 (Plant Extracts); 0 (Protective Agents); 04ZR38536J (oxaliplatin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170221
[Lr] Data última revisão:
170221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE


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[PMID]:27697724
[Au] Autor:Wang Y; Zhao J; Di T; Wang M; Ruan Z; Zhang L; Xie X; Meng Y; Lin Y; Liu X; Wang N; Li P
[Ad] Endereço:Beijing Hospital of Traditional Chinese Medicine, affiliated with Capital Medical University, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China.
[Ti] Título:Suppressive effect of ß,ß-dimethylacryloyl alkannin on activated dendritic cells in psoriasis by the TLR7/8 pathway.
[So] Source:Int Immunopharmacol;40:410-418, 2016 Nov.
[Is] ISSN:1878-1705
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:ß,ß-dimethylacryloyl alkannin (DMA) is a key component of Lithospermum and possesses good efficacy for treating psoriasis. DMA inhibits activated dendritic cells (DCs), but the mechanism is unknown. Therefore, this study aimed to explore the modulation of the TLR7/8 pathway by DMA in psoriasis-activated DCs. Models of psoriasis-like skin lesions were established using BALB/c mice; 8 mice were treated with DMA (2.5mg/kg). Bone marrow cells were isolated and induced into DCs using R848, a TLR7/8 agonist. Splenic CD11c+ cells were detected by flow cytometry. Skin CD11c+ cells were detected by immunofluorescence. TLR7, TLR8, MYD88, and IRAKM proteins were detected by Western blot. The effects of DMA on surface molecules of DCs were observed by flow cytometry. mRNA expression of inflammatory factors was detected by qRT-PCR. Secreted cytokines were detected by cytometric bead array. Compared with the model group, psoriasis-like skin lesions were alleviated by DMA, the splenic CD11c+ cells were significantly decreased (P<0.01), and CD11c+ cell numbers in skin lesions were decreased (P<0.01). Expression levels of TLR7, MYD88, and IRAKM were significantly decreased (P<0.05). R848-stimulated DCs showed increased expression of I-A/I-E, CD80, and CD86 (P<0.01), increased IL-23 and IL-1ß mRNA and secretion (P<0.05), and increased TLR7, TLR8, MYD88, and IRAKM expression (P<0.01); DMA inhibited all of these effects of the TLR7/8 pathway activation by R848 (P<0.05). In conclusion, DMA could inhibit psoriasis-activated DCs via the TLR7/8 pathway.
[Mh] Termos MeSH primário: Células Dendríticas/efeitos dos fármacos
Lithospermum
Glicoproteínas de Membrana/metabolismo
Naftoquinonas/uso terapêutico
Psoríase/tratamento farmacológico
Pele/efeitos dos fármacos
Receptor 7 Toll-Like/metabolismo
Receptor 8 Toll-Like/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular/efeitos dos fármacos
Células Cultivadas
Células Dendríticas/imunologia
Modelos Animais de Doenças
Seres Humanos
Imidazóis/farmacologia
Quinases Associadas a Receptores de Interleucina-1/metabolismo
Interleucina-1beta/genética
Interleucina-1beta/metabolismo
Interleucina-23/genética
Interleucina-23/metabolismo
Masculino
Glicoproteínas de Membrana/agonistas
Camundongos
Camundongos Endogâmicos BALB C
Fator 88 de Diferenciação Mieloide/metabolismo
Naftoquinonas/química
Pele/imunologia
Receptor 7 Toll-Like/agonistas
Receptor 8 Toll-Like/agonistas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Imidazoles); 0 (Interleukin-1beta); 0 (Interleukin-23); 0 (Membrane Glycoproteins); 0 (Myd88 protein, mouse); 0 (Myeloid Differentiation Factor 88); 0 (Naphthoquinones); 0 (TLR8 protein, mouse); 0 (Tlr7 protein, mouse); 0 (Toll-Like Receptor 7); 0 (Toll-Like Receptor 8); 0 (beta,beta-dimethylacryloyl alkannin); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases); EC 2.7.11.1 (Irak3 protein, mouse); V3DMU7PVXF (resiquimod)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170417
[Lr] Data última revisão:
170417
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161005
[St] Status:MEDLINE


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[PMID]:27548143
[Au] Autor:Lee DY; Choi SI; Han SH; Lee YJ; Choi JG; Lee YS; Choi JH; Lee SE; Kim GS
[Ad] Endereço:Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Korea. dylee0809@gmail.com.
[Ti] Título:Potential of Pseudoshikonin I Isolated from Lithospermi Radix as Inhibitors of MMPs in IL-1ß-Induced SW1353 Cells.
[So] Source:Int J Mol Sci;17(8), 2016 Aug 18.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Pseudoshikonin I, the new bioactive constituent of Lithospermi radix, was isolated from this methanol extract by employing reverse-phase medium-pressure liquid chromatography (MPLC) using acetonitrile/water solvent system as eluents. The chemical structure was determined based on spectroscopic techniques, including 1D NMR (¹H, (13)C, DEPT), 2D NMR (gCOSY, gHMBC, gHMQC), and QTOF/MS data. In this study, we demonstrated the effect of pseudoshikonin I on matrix-metalloproteinase (MMPs) activation and expression in interleukin (IL)-1ß-induced SW1353 chondrosarcoma cells. MMPs are considered important for the maintenance of the extracellular matrix. Following treatment with PS, active MMP-1, -2, -3, -9, -13 and TIMP-2 were quantified in the SW1353 cell culture supernatants using a commercially available ELISA kit. The mRNA expression of MMPs in SW1353 cells was measured by RT-PCR. Pseudoshikonin I treatment effectively protected the activation on all tested MMPs in a dose-dependent manner. TIMP-2 mRNA expression was significantly upregulated by pseudoshikonin I treatment. Overall, we elucidated the inhibitory effect of pseudoshikonin on MMPs, and we suggest its use as a potential novel anti-osteoarthritis agent.
[Mh] Termos MeSH primário: Interleucina-1beta/farmacologia
Lithospermum/química
Inibidores de Metaloproteinases de Matriz/farmacologia
Metaloproteinases da Matriz/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Espectroscopia de Ressonância Magnética
Metaloproteinase 1 da Matriz/metabolismo
Metaloproteinase 13 da Matriz/metabolismo
Metaloproteinase 3 da Matriz/metabolismo
Metaloproteinase 9 da Matriz/metabolismo
Inibidores de Metaloproteinases de Matriz/química
Estrutura Molecular
Inibidor Tecidual de Metaloproteinase-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-1beta); 0 (Matrix Metalloproteinase Inhibitors); 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2); EC 3.4.24.- (Matrix Metalloproteinase 13); EC 3.4.24.- (Matrix Metalloproteinases); EC 3.4.24.17 (Matrix Metalloproteinase 3); EC 3.4.24.35 (Matrix Metalloproteinase 9); EC 3.4.24.7 (Matrix Metalloproteinase 1)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170417
[Lr] Data última revisão:
170417
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160823
[St] Status:MEDLINE


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[PMID]:27353217
[Au] Autor:Choi YH; Kim GS; Choi JH; Jin SW; Kim HG; Han Y; Lee DY; Choi SI; Kim SY; Ahn YS; Lee KY; Jeong HG
[Ad] Endereço:College of Pharmacy, Chonnam National University, Gwangju 500-757, Republic of Korea.
[Ti] Título:Ethanol extract of Lithospermum erythrorhizon Sieb. et Zucc. promotes osteoblastogenesis through the regulation of Runx2 and Osterix.
[So] Source:Int J Mol Med;38(2):610-8, 2016 Aug.
[Is] ISSN:1791-244X
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Bone remodeling and homeostasis are largely the result of the coordinated action of osteoblasts and osteoclasts. Osteoblasts are responsible for bone formation. The differentiation of osteoblasts is regulated by the transcription factors, Runx2 and Osterix. Natural products of plant origin are still a major part of traditional medicinal systems in Korea. The root of Lithospermum erythrorhizon Sieb. et Zucc. (LR), the purple gromwell, is an herbal medicine used for inflammatory and infectious diseases. LR is an anti-inflammatory and exerts anticancer effects by inducing the apoptosis of cancer cells. However, the precise molecular signaling mechanisms of osteoblastogenesis as regards LR and osteoblast transcription are not yet known. In this study, we investigated the effects of ethanol (EtOH) extract of LR (LES) on the osteoblast differentiation of C2C12 myoblasts induced by bone morphogenetic protein 4 (BMP4) and the potential involvement of Runx2 and Osterix in these effects. We found that the LES exhibited an ability to induce osteoblast differentiation. LES increased the expression of the osteoblast marker, alkaline phosphatase (ALP), as well as its activity, as shown by ALP staining and ALP activity assay. LES also increased mineralization, as shown by Alizarin Red S staining. Treatment with LES increased the protein levels (as shown by immunoblotting), as well as the transcriptional activity of Runx2 and Osterix and enhanced osteogenic activity. These results suggest that LES modulates osteoblast differentiation at least in part through Runx2 and Osterix.
[Mh] Termos MeSH primário: Subunidade alfa 1 de Fator de Ligação ao Core/genética
Etanol/química
Regulação da Expressão Gênica/efeitos dos fármacos
Lithospermum/química
Osteoblastos/metabolismo
Osteogênese/efeitos dos fármacos
Extratos Vegetais/farmacologia
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Proteína Morfogenética Óssea 4/farmacologia
Diferenciação Celular/efeitos dos fármacos
Diferenciação Celular/genética
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
Células HEK293
Seres Humanos
Camundongos
Osteoblastos/citologia
Osteoblastos/efeitos dos fármacos
Osteogênese/genética
Fator de Transcrição Sp7
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Bone Morphogenetic Protein 4); 0 (Core Binding Factor Alpha 1 Subunit); 0 (Plant Extracts); 0 (Sp7 Transcription Factor); 0 (Sp7 protein, mouse); 0 (Transcription Factors); 3K9958V90M (Ethanol)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160630
[St] Status:MEDLINE
[do] DOI:10.3892/ijmm.2016.2655


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[PMID]:27230755
[Au] Autor:Fang R; Zou A; Zhao H; Wu F; Zhu Y; Zhao H; Liao Y; Tang RJ; Pang Y; Yang R; Wang X; Qi J; Lu G; Yang Y
[Ad] Endereço:State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210046, People's Republic of China.
[Ti] Título:Transgenic studies reveal the positive role of LeEIL-1 in regulating shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.
[So] Source:BMC Plant Biol;16(1):121, 2016 May 26.
[Is] ISSN:1471-2229
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The phytohormone ethylene (ET) is a key signaling molecule for inducing the biosynthesis of shikonin and its derivatives, which are secondary metabolites in Lithospermum erythrorhizon. Although ETHYLENE INSENSITIVE3 (EIN3)/EIN3-like proteins (EILs) are crucial transcription factors in ET signal transduction pathway, the possible function of EIN3/EIL1 in shikonin biosynthesis remains unknown. In this study, by targeting LeEIL-1 (L. erythrorhizon EIN3-like protein gene 1) at the expression level, we revealed the positive regulatory effect of LeEIL-1 on shikonin formation. RESULTS: The mRNA level of LeEIL-1 was significantly up-regulated and down-regulated in the LeEIL-1-overexpressing hairy root lines and LeEIL-1-RNAi hairy root lines, respectively. Specifically, LeEIL-1 overexpression resulted in increased transcript levels of the downstream gene of ET signal transduction pathway (LeERF-1) and a subset of genes for shikonin formation, excretion and/or transportation (LePAL, LeC4H-2, Le4CL-1, HMGR, LePGT-1, LeDI-2, and LePS-2), which was consistent with the enhanced shikonin contents in the LeEIL-1-overexpressing hairy root lines. Conversely, LeEIL-1-RNAi dramatically repressed the expression of the above genes and significantly reduced shikonin production. CONCLUSIONS: The results revealed that LeEIL-1 is a positive regulator of the biosynthesis of shikonin and its derivatives in L. erythrorhizon hairy roots. Our findings gave new insights into the molecular regulatory mechanism of ET in shikonin biosynthesis. LeEIL-1 could be a crucial target gene for the genetic engineering of shikonin biosynthesis.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica de Plantas
Lithospermum/genética
Naftoquinonas/metabolismo
Proteínas de Plantas/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Lithospermum/metabolismo
Proteínas de Plantas/metabolismo
Raízes de Plantas/metabolismo
Plantas Geneticamente Modificadas/genética
Plantas Geneticamente Modificadas/metabolismo
Interferência de RNA
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Naphthoquinones); 0 (Plant Proteins); 0 (Transcription Factors); 3IK6592UBW (shikonin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160528
[St] Status:MEDLINE
[do] DOI:10.1186/s12870-016-0812-6


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[PMID]:26780904
[Au] Autor:Fang R; Wu F; Zou A; Zhu Y; Zhao H; Zhao H; Liao Y; Tang RJ; Yang T; Pang Y; Wang X; Yang R; Qi J; Lu G; Yang Y
[Ad] Endereço:State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210093, People's Republic of China.
[Ti] Título:Transgenic analysis reveals LeACS-1 as a positive regulator of ethylene-induced shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.
[So] Source:Plant Mol Biol;90(4-5):345-58, 2016 Mar.
[Is] ISSN:1573-5028
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The phytohormone ethylene (ET) is a crucial signaling molecule that induces the biosynthesis of shikonin and its derivatives in Lithospermum erythrorhizon shoot cultures. However, the molecular mechanism and the positive regulators involved in this physiological process are largely unknown. In this study, the function of LeACS-1, a key gene encoding the 1-aminocyclopropane-1-carboxylic acid synthase for ET biosynthesis in L. erythrorhizon hairy roots, was characterized by using overexpression and RNA interference (RNAi) strategies. The results showed that overexpression of LeACS-1 significantly increased endogenous ET concentration and shikonin production, consistent with the up-regulated genes involved in ET biosynthesis and transduction, as well as the genes related to shikonin biosynthesis. Conversely, RNAi of LeACS-1 effectively decreased endogenous ET concentration and shikonin production and down-regulated the expression level of above genes. Correlation analysis showed a significant positive linear relationship between ET concentration and shikonin production. All these results suggest that LeACS-1 acts as a positive regulator of ethylene-induced shikonin biosynthesis in L. erythrorhizon hairy roots. Our work not only gives new insights into the understanding of the relationship between ET and shikonin biosynthesis, but also provides an efficient genetic engineering target gene for secondary metabolite production in non-model plant L. erythrorhizon.
[Mh] Termos MeSH primário: Etilenos/farmacologia
Regulação da Expressão Gênica de Plantas/fisiologia
Lithospermum/metabolismo
Liases/metabolismo
Naftoquinonas/metabolismo
Raízes de Plantas/metabolismo
[Mh] Termos MeSH secundário: Clonagem Molecular
Biologia Computacional
DNA Complementar/genética
DNA Complementar/metabolismo
Liases/genética
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Raízes de Plantas/efeitos dos fármacos
Plantas Geneticamente Modificadas
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (Ethylenes); 0 (Naphthoquinones); 0 (Plant Proteins); 3IK6592UBW (shikonin); 91GW059KN7 (ethylene); EC 4.- (Lyases); EC 4.4.1.14 (1-aminocyclopropanecarboxylate synthase)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160120
[St] Status:MEDLINE
[do] DOI:10.1007/s11103-015-0421-z



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