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1.
Int J Mol Sci ; 24(23)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38068895

RESUMO

Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.


Assuntos
Endotoxemia , Kadsura , Lignanas , Piper , Camundongos , Animais , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Kadsura/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Interleucina-6/genética , Interleucina-6/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inflamação/metabolismo , Lignanas/uso terapêutico
2.
Plant Sci ; 324: 111458, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36084765

RESUMO

Fruit color, as an important appearance attribute, is crucial for attracting consumers. However, the underlying mechanism regulating mature fruit color formation in Kadsura coccinea remains unclear. Here, a comprehensive metabolomics and transcriptomics analysis was performed to investigate the molecular mechanisms of anthocyanin accumulation between two K. coccinea cultivars with different mature fruit colors-'Dahong No. 1' (red) and 'Jinhu' (yellow). Targeted metabolomic analysis revealed high anthocyanin levels, most of which were cyanidin and delphinidin derivatives, in 'Dahong No. 1' mature fruit peel. The SNP analysis indicated that the two different cultivars had similar genetic background. Moreover, comparative transcriptomic analysis demonstrated that differentially expressed genes (DEGs) were related to flavonoid biosynthesis and metabolic process in the two K. coccinea cultivars. Gene expression profiling data showed that the structural and regulatory genes associated with anthocyanin biosynthesis were significantly upregulated in 'Dahong No. 1' mature fruit peel, which was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Notably, the key anthocyanin activator KcMYB1 was identified, which was significantly upregulated in 'Dahong No. 1' compared with 'Jinhu'. We further confirmed that KcMYB1 actively regulated the accumulation of anthocyanin by ectopic expression in vivo. Furthermore, allelic constitution of KcMYB1 in K. coccinea were investigated. The present study can provide insights for understanding the regulatory mechanisms of anthocyanin differential accumulation in the mature fruits of K. coccinea.


Assuntos
Antocianinas , Kadsura , Antocianinas/metabolismo , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Kadsura/metabolismo , Proteínas de Plantas/metabolismo , Transcriptoma
3.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34751410

RESUMO

Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and anti­melanogenic effects were investigated against the background of skin photoprotective and anti­melanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVA­and UVB­irradiated keratinocytes and α­melanocyte stimulating hormone (α­MSH)­stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant anti­apoptotic effects on UVA­and UVB­irradiated keratinocytes. After α­MSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the α­MSH­induced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmia­associated transcription factor (MITF), tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2 in α­MSH­stimulated melanocytes. In addition, gomisin D markedly downregulated α­MSH­induced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP­1 and TRP­2 genes. Overall, gomisin D has photoprotective and anti­melanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.


Assuntos
Dioxóis/farmacologia , Lignanas/farmacologia , Compostos Policíclicos/farmacologia , Protetores contra Radiação/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , China , Células HaCaT , Humanos , Kadsura/metabolismo , Queratinócitos/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/metabolismo
4.
Phytochemistry ; 158: 56-66, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30476897

RESUMO

Highly oxygenated schitriterpenoids are interesting for study of their structures, bioactivities and synthesis. From Kadsura angustifolia fermented by an associated symbiotic endophytic fungus, Penicillium sp. SWUKD4.1850, nine undescribed triterpenoids, kadhenrischinins A-H, and 7ß-schinalactone C together with four known triterpenoids, henrischinins A and B, schinalactone C and nigranoic acid were isolated and established by the extensive 1D-, 2D-NMR, HR-ESI-MS and ECD data analysis. Except nigranoic acid, all these metabolites have been first detected in non-fermented K. angustifolia. Structurally, kadhenrischinins A-D belong to the relatively rare class of highly oxygenated schitriterpenoids that contain a unique 3-one-2-oxabicyclo [3,2,1]-octane motif, while kadhenrischinins E-H feature a cyclopentane ring in a side chain rarely found in the family Schisandraceae. These results indicated that fermentation of K. angustifolia with SWUKD4.1850 induced the production of highly oxygenated schitriterpenoids from nigranoic acid, which provided a guidance to obtain desired compounds from those plants initially thought not to produce. This is the first report on the fermentation of K. angustifolia medical plant and the first discovery of highly oxygenated schitriterpenoids by microbial technology.


Assuntos
Kadsura/metabolismo , Kadsura/microbiologia , Penicillium/fisiologia , Triterpenos/química , Triterpenos/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Endófitos/fisiologia , Fermentação , Células Hep G2 , Humanos , Kadsura/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Simbiose , Triterpenos/farmacologia
5.
Phytochemistry ; 72(18): 2385-95, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21889177

RESUMO

A petroleum ether extract of Kadsura longipedunculata enhanced the GABA-induced chloride current (I(GABA)) by 122.5±0.3% (n=2) when tested at 100 µg/ml in Xenopuslaevis oocytes expressing GABA A receptors (α(1)ß(2)γ(2S) subtype) in two-microelectrode voltage clamp measurements. Thirteen compounds were subsequently identified by HPLC-based activity profiling as responsible for GABA A receptor activity and purified in preparative scale. 6-Cinnamoyl-6,7-dihydro-7-myrceneol and 5,6-dihydrocuparenic acid were thereby isolated for the first time. The determination of the absolute stereochemistry of these compounds was achieved by comparison of experimental and calculated ECD spectra. All but one of the 13 isolated compounds from K. longipedunculata potentiated I(GABA) through GABA A receptors composed of α(1)ß(2)γ(2S) subunits in a concentration-dependent manner. Potencies ranged from 12.8±3.1 to 135.6±85.7 µM, and efficiencies ranged from 129.7±36.8% to 885.8±291.2%. The phytochemical profiles of petroleum ether extracts of Kadsura japonica fruits (114.1±2.6% potentiation of I(GABA) at 100 µg/ml, n=2), and Schisandra chinensis fruits (inactive at 100 µg/ml) were compared by HPLC-PDA-ESIMS with that of K. longipedunculata.


Assuntos
GABAérgicos/química , Kadsura/química , Receptores de GABA-A/química , Animais , Cromatografia Líquida de Alta Pressão , GABAérgicos/isolamento & purificação , GABAérgicos/farmacologia , Kadsura/metabolismo , Oócitos/efeitos dos fármacos , Técnicas de Patch-Clamp , Extratos Vegetais/química , Xenopus laevis
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