Extensive phytochemical analysis of the CHCl3-soluble part of an ethanolic extract of branches and twigs of Broussonetia papyrifera led to the isolation of fourteen compounds, including a novel 5,11-dioxabenzo[b]fluoren-10-one derivative named broussofluorenone C (12). The isolated compounds 1-14 were characterized based on their NMR and HRMS data, and examined for their anti-inflammatory activities in LPS-stimulated THP-1 cells as well as for their cellular antioxidant effects. Compounds 7-10 and 12 showed inhibitory effects on NF-κB/AP-1 activation and compounds 7-9 were subsequently confirmed to suppress the secretion of both IL-1β and TNF-α in LPS-stimulated THP-1 cells more significantly than the prednisone used as a positive control. In the CAA assay, compound 10 exhibited the greatest antioxidant effect, greater than that of the quercetin used as a positive control. The results show possible beneficial effects and utilization of B. papyrifera wood in the treatment of inflammatory diseases as well as oxidative stress.

• MeSH
• antiflogistika chemie   izolace a purifikace   farmakologie   MeSH
• antioxidancia chemie   izolace a purifikace   farmakologie   MeSH
• Broussonetia chemie   MeSH
• interleukin-1beta antagonisté a inhibitory   biosyntéza   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy antagonisté a inhibitory   farmakologie   MeSH
• molekulární struktura MeSH
• NF-kappa B analýza   antagonisté a inhibitory   biosyntéza   MeSH
• oxidační stres účinky léků   MeSH
• THP-1 buňky MeSH
• TNF-alfa antagonisté a inhibitory   biosyntéza   MeSH
• transkripční faktor AP-1 analýza   antagonisté a inhibitory   biosyntéza   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Here we report the comprehensive characterization of the secondary metabolites from the leaves of Colebrookea oppositifolia Smith, a species used as medicinal plant in the traditional medicine of Nepal. Phytochemical screening of bioactives was performed using an integrated LC-MSn and high resolution MS (Mass Spectrometry) approach. Forty-three compounds were tentatively identified, mainly aglyconic and glycosilated flavonoids and phenolic acids, as well as other bioactives such as coumarins and terpenes were detected. Furthermore, the NF-κB and AP-1 inhibitory activity of C. oppositifolia extract were evaluated, as well as its cytotoxicity against THP-1 cells, in order to assess the potential use of this herb as a source of anti-inflammatory and cytotoxic compounds. The results so far obtained indicate that C. oppositifolia leaves extract could significantly reduce the viability of THP-1 cells (IC50 = 6.2 ± 1.2 µg/mL), as well as the activation of both NF-κB and AP-1 at the concentration of 2 μg/mL. Our results indicate that Nepalese C. oppositifolia is a valuable source of anti-inflammatory and cytotoxic compounds. The phytochemical composition reported here can partially justify the traditional uses of C. oppositifolia in Nepal, especially in the treatment of inflammatory diseases, although further research will be needed to assess the full potential of this species.

• MeSH
• antiflogistika izolace a purifikace   farmakologie   toxicita   MeSH
• chromatografie kapalinová MeSH
• flavonoidy analýza   izolace a purifikace   MeSH
• hluchavkovité metabolismus   MeSH
• hmotnostní spektrometrie MeSH
• hydroxybenzoáty analýza   izolace a purifikace   MeSH
• léčivé rostliny metabolismus   MeSH
• lidé MeSH
• listy rostlin metabolismus   MeSH
• metabolom MeSH
• methanol MeSH
• NF-kappa B antagonisté a inhibitory   MeSH
• rostlinné extrakty chemie   izolace a purifikace   farmakologie   toxicita   MeSH
• THP-1 buňky MeSH
• transkripční faktor AP-1 antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Nepál MeSH

Stilbenoids are important components of foods (e.g., peanuts, grapes, various edible berries), beverages (wine, white tea), and medicinal plants. Many publications have described the anti-inflammatory potential of stilbenoids, including the widely known trans-resveratrol and its analogues. However, comparatively little information is available regarding the activity of their prenylated derivatives. One new prenylated stilbenoid (2) was isolated from Artocarpus altilis and characterized structurally based on 1D and 2D NMR analysis and HRMS. Three other prenylated stilbenoids were prepared synthetically (9-11). Their antiphlogistic potential was determined by testing them together with known natural prenylated stilbenoids from Macaranga siamensis and Artocarpus heterophyllus in both cell-free and cell assays. The inhibition of 5-lipoxygenase (5-LOX) was also shown by simulated molecular docking for the most active stilbenoids in order to elucidate the mode of interaction between these compounds and the enzyme. Their effects on the pro-inflammatory nuclear factor-κB (NF-κB) and the activator protein 1 (AP-1) signaling pathway were also analyzed. The THP1-XBlue-MD2-CD14 cell line was used as a model for determining their anti-inflammatory potential, and lipopolysaccharide (LPS) stimulation of Toll-like receptor 4 induced a signaling cascade leading to the activation of NF-κB/AP-1. The ability of prenylated stilbenoids to attenuate the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was further evaluated using LPS-stimulated THP-1 macrophages.

• MeSH
• buněčné linie MeSH
• cyklooxygenasy metabolismus   MeSH
• inhibitory enzymů farmakologie   MeSH
• lidé MeSH
• lipoxygenasy metabolismus   MeSH
• NF-kappa B antagonisté a inhibitory   MeSH
• prenylace * MeSH
• signální transdukce účinky léků   MeSH
• stilbeny farmakologie   MeSH
• transkripční faktor AP-1 antagonisté a inhibitory   MeSH
• zánět prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hypericum japonicum Thunb. ex Murray is traditionally used in Nepal to treat several diseases, among whom inflammation and acute pain. Although several secondary metabolites from the same Hypericum species have been already characterized and considered for their pharmacological use, an exhaustive phytochemical characterization of H. japonicum from Nepal is lacking, as well as the assessment of its potential pharmacological properties. Hence, the aims of this study were the characterization of a methanolic extract of H. japonicum (HJME) collected from the Northern region of Nepal by LC-MSn and UPLC-QTOF. The assessment of in vitro inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) transcription factors and HJME's cytotoxic effect on human cell lines was performed to evaluate the potential use of this herb as a source of anti-inflammatory and cytotoxic lead compounds. Fifty-seven phytoconstituents were identified, being mainly flavonoids, phloroglucinols, phenolic acids and xanthones. Although compounds characteristic of H. japonicum were detected (quercetin, quercetin-7-O-α-l-rhamnoside, quercitrin and hyperoside), several others are here reported for the first time in this species. The results from bioassays indicated that HJME could significantly reduce the viability of human THP-1 cells (IC50 = 5.4 ± 1.1 μg mL-1), showing the promising potential of HJME as anti-tumor agent. Furthermore, HJME significantly decreased the activation of both NF-κB and AP-1 at the concentration of 2 μg mL-1. Overall, these data suggest that H. japonicum from Nepal could be used as a source of potential natural anti-inflammatory and anti-tumor lead compounds.

• MeSH
• antiflogistika farmakologie   MeSH
• antitumorózní látky farmakologie   MeSH
• biotest MeSH
• buněčné linie MeSH
• chromatografie kapalinová MeSH
• flavonoidy farmakologie   MeSH
• floroglucinol farmakologie   MeSH
• hmotnostní spektrometrie MeSH
• hydroxybenzoáty farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• lidé MeSH
• NF-kappa B - podjednotka p50 antagonisté a inhibitory   MeSH
• rostlinné extrakty farmakologie   MeSH
• THP-1 buňky MeSH
• transkripční faktor AP-1 antagonisté a inhibitory   MeSH
• třezalka chemie   MeSH
• viabilita buněk MeSH
• xantony farmakologie   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Nepál MeSH