Diplacone (1) and mimulone (2), two geranylated flavanones, have previously shown anti-inflammatory and antiradical activity in vitro. The present study aimed to evaluate their activity in vivo on a model of colitis induced in Wistar rats by an oral administration of dextran sulfate sodium (DSS). Diplacone (1) and mimulone (2) were administered at a bolus dose of 25mg/kg by gastric gavage 48 and 24h prior to the induction of colitis by DSS and every 24h on the following days of the experiment. The effect of the treatment was assessed by monitoring the disease activity index (DAI), histopathological examination, evaluation of the weight and length of the colon and by analysis of the levels and activities of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP2), superoxide dismutase-2 (SOD2), and catalase (CAT) in the inflamed tissue. Administration of the test compounds prior and after induction of colitis ameliorated the symptoms of colitis (diarrhea, presence of the blood in the stool) and delayed their onset. The ability of compounds 1 and 2 to reduce the levels of COX-2 and to increase the ratio of pro-MMP2/MMP2 activity correlates with the values of the DAI. The lowering of the levels of the antioxidant enzymes SOD2 and CAT reflects the ability of the test compounds to scavenge reactive oxygen species.

• MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• flavanony farmakologie   MeSH
• katalasa metabolismus   MeSH
• kolitida chemicky indukované   farmakoterapie   MeSH
• kolon účinky léků   patofyziologie   MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• molekulární struktura MeSH
• potkani Wistar MeSH
• síran dextranu škodlivé účinky   MeSH
• superoxiddismutasa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Flavonoids are commonly studied for their anti-inflammatory effects; however, this is the first paper describing the possible antiphlogistic activity of a geranylated flavanone. This study focused on the ability of diplacone to modulate the gene expression of pro-inflammatory tumour necrosis factor alpha and monocyte chemoattractant protein 1, and of anti-inflammatory zinc finger protein 36. The action of diplacone was also compared with that of conventional drug indomethacin. Human monocyte-derived macrophages of the human monocytic leukaemia cell line were pretreated with diplacone or indomethacin. Subsequently, inflammatory reaction was induced by lipopolysaccharide, and changes of tumour necrosis factor alpha, monocyte chemoattractant protein 1 and zinc finger protein 36 gene expression at the transcriptional level were measured. In this model, diplacone significantly down-regulated the expression of tumour necrosis factor alpha and monocyte chemoattractant protein 1 and up-regulated the zinc finger protein 36 expression. This makes diplacone a promising molecule for treatment of the inflammatory stage of diseases. The effect of diplacone in decreasing lipopolysaccharide-induced inflammatory gene expression is in many ways similar to that of the conventional drug indomethacin.

• MeSH
• buněčné linie MeSH
• chemokin CCL2 genetika   MeSH
• financování organizované MeSH
• flavonoidy farmakologie   chemie   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• makrofágy metabolismus   účinky léků   MeSH
• molekulární struktura MeSH
• TNF-alfa genetika   MeSH
• Check Tag
• lidé MeSH

Geranylovaný flavanon diplakon je látka izolovaná z Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) vykazující protizánětlivé a antioxidační vlastnosti a také vysokou lipofilitu a nízkou rozpustnost ve vodě. Jako modelová molekula byl proto použit k inkorporaci do glukanových částic (GP) s cílem zvýšit jeho potenciální biodostupnost. GP jsou v principu duté schránky připravené čištěním kvasinek Saccharomyces cerevisiae pro získání buněčné stěny, obsahující převážně β-(1→3)/β-(1→6) glukan. Cílem práce je porovnat antiflogistické působení kompozitů diplakonu a glukanového nosiče s působením samotné látky, samotných glukanových částic a fyzické směsi čistých glukanových částic s čistým diplakonem. Na buněčné linii odvozené z lidských leukemických monocytů THP1-XBlueTM-MD2-CD14 byla simulována zánětlivá reakce stimulací buněk lipopolysacharidem (LPS) z Escherichia coli. Kompozity GP a diplakonu signifikantně snížily aktivitu prozánětlivých transkripčních faktorů nukleárního faktoru κB (NF-κB) a aktivátorového proteinu 1 (AP-1) v porovnání s čistou látkou.

Geranylated flavanone diplacone is a flavanone isolated from Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) with anti-inflammatory and antioxidant properties, nevertheless showing high lipophilicity and low solubility in water. Diplacone was therefore used as a model molecule for incorporation into glucan particles (GPs). GPs are prepared by intensive washing of yeast (Saccharomyces cerevisiae) leading to hollow shells consisting of β-(1→3)/β-(1→6) glucan mainly. The aim of this study was to compare anti-inflammatory potential of GPs-diplacone composites with the compound itself, GPs themselves and the physical mixture of GPs and diplacone. The cell line THP1-XBlueTM-MD2-CD14 derived from human leukemic monocytes was stimulated with lipopolysaccharide (LPS) from Escherichia coli to trigger inflammatory reaction. The composites of GPs with diplacone significantly decreased the activity of pro-inflammatory transcription factors nuclear factor κB (NF-κB) and activator protein 1 (AP-1).

• Klíčová slova
• diplakon,
• MeSH
• enkapsulace buněk MeSH
• glukany terapeutické užití   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• zánět * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.

• MeSH
• antiflogistika farmakologie   chemie   MeSH
• autofagie účinky léků   MeSH
• flavanony * farmakologie   chemie   MeSH
• komplexní sloučeniny * farmakologie   chemická syntéza   chemie   MeSH
• lidé MeSH
• měď * chemie   farmakologie   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk * účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Natural compounds offer a wide spectrum of potential active substances, but often they have a poor bioavailability. To increase the bioavailability and bioactivity of the natural anti-inflammatory molecules curcumin and diplacone, we used glucan particles (GPs), hollow shells from Saccharomyces cerevisiae composed mainly of β-1,3-d-glucan. Their indigestibility and relative stability in the gut combined with their immunomodulatory effects makes them promising carriers for such compounds. This study aimed to determine how curcumin and diplacone, either alone or incorporated in GPs, affect the immunomodulatory activity of the latter by assessing the respiratory burst response and the secretion of pro-inflammatory cytokines by primary porcine innate immune cells. Incorporating curcumin and diplacone into GPs by controlled evaporation of the organic solvent substantially reduced the respiratory burst response mediated by GPs. Incorporated curcumin in GPs also reduced GPs mediated secretion of IL-1β and TNF-α by innate immune cells. The obtained results indicate a potentially beneficial effect of the incorporation of curcumin or diplacone into GPs against inflammation.

• MeSH
• antiflogistika chemie   farmakologie   MeSH
• beta-glukany chemie   izolace a purifikace   farmakologie   MeSH
• flavanony chemie   farmakologie   MeSH
• imunologické faktory chemie   izolace a purifikace   farmakologie   MeSH
• interleukin-1beta metabolismus   MeSH
• kultivované buňky MeSH
• kurkumin chemie   farmakologie   MeSH
• leukocyty mononukleární účinky léků   imunologie   metabolismus   MeSH
• neutrofily účinky léků   imunologie   metabolismus   MeSH
• nosiče léků * MeSH
• příprava léků MeSH
• respirační vzplanutí účinky léků   MeSH
• rozpouštědla chemie   MeSH
• Saccharomyces cerevisiae chemie   MeSH
• Sus scrofa MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

In this study, four prenylated and geranylated flavonoids, cudraflavone B (1), pomiferin (2), osajin (3), and diplacone (4), were tested for their antioxidant and anti-inflammatory effects and to identify any potential relationships between chemical structure and antioxidant or anti-inflammatory properties. The selected flavonoids were examined in cell-free models to prove their ability to scavenge superoxide radicals, hydrogen peroxide, and hypochlorous acid. Further, the ability of the flavonoids to influence the formation of reactive oxygen species in the murine macrophage cell line J774.A1 was tested in the presence and absence of lipopolysaccharide (LPS). The ability of flavonoids to inhibit LPS-induced IκB-α degradation and COX-2 expression was used as a model for the inflammatory response. The present results indicated that the antioxidant activity was dependent on the chemical structure, where the catechol moiety is especially crucial for this effect. The most potent antioxidant activities in cell-free models were observed for diplacone (4), whereas cudraflavone B (1) and osajin (3) showed a pro-oxidant effect in J774.A1 cells. All flavonoids tested were able to inhibit IκB-α degradation, but only diplacone (4) also down-regulated COX-2 expression.

• MeSH
• antiflogistika farmakologie   MeSH
• antioxidancia farmakologie   MeSH
• benzopyrany chemie   farmakologie   MeSH
• cyklooxygenasa 2 účinky léků   MeSH
• flavonoidy chemie   farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• isoflavony chemie   farmakologie   MeSH
• kinasa I-kappa B antagonisté a inhibitory   MeSH
• lipopolysacharidy farmakologie   MeSH
• makrofágy účinky léků   MeSH
• myši MeSH
• oxid dusnatý biosyntéza   MeSH
• prenylace MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: Oxidative stress is a key factor in the pathophysiology of many diseases. This study aimed to verify the antioxidant activity of selected plant phenolics in cell-based assays and determine their direct or indirect effects. Methods: The cellular antioxidant assay (CAA) assay was employed for direct scavenging assays. In the indirect approach, the influence of each test substance on the gene and protein expression and activity of selected antioxidant enzymes was observed. One assay also dealt with activation of the Nrf2-ARE pathway. The overall effect of each compound was measured using a glucose oxidative stress protection assay. Results: Among the test compounds, acteoside showed the highest direct scavenging activity and no effect on the expression of antioxidant enzymes. It increased only the activity of catalase. Diplacone was less active in direct antioxidant assays but positively affected enzyme expression and catalase activity. Morusin showed no antioxidant activity in the CAA assay. Similarly, pomiferin had only mild antioxidant activity and proved rather cytotoxic. Conclusions: Of the four selected phenolics, only acteoside and diplacone demonstrated antioxidant effects in cell-based assays.

• MeSH
• antioxidační responzivní elementy MeSH
• antioxidancia chemie   farmakologie   MeSH
• biologické markery MeSH
• exprese genu MeSH
• faktor 2 související s NF-E2 genetika   metabolismus   MeSH
• fenoly chemie   farmakologie   MeSH
• glukosa MeSH
• lidé MeSH
• molekulární struktura MeSH
• oxidační stres MeSH
• protinádorové látky chemie   farmakologie   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• superoxiddismutasa 1 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Five geranylflavonoids, one prenylated flavonoid, and a simple flavanone were isolated from an ethanolic extract of Paulownia tomentosa fruit. Tomentodiplacol (1), 3'-O-methyl-5'-methoxydiplacol (2), 6-isopentenyl-3'-O-methyltaxifolin (3), and dihydrotricin (4) are reported from a natural source for the first time and 3'-O-methyldiplacone (6) for the first time from the genus Paulownia. The structures of the compounds were determined by mass spectrometry, including HRMS, and by 1D and 2D NMR spectroscopy. The cytotoxicity and DPPH (2,2-diphenyl-1-picrylhydrazyl)-quenching activity of some of these compounds were tested, with diplacone proving to be the best antioxidant, although the most cytotoxic compound.

• MeSH
• bifenylové sloučeniny MeSH
• financování organizované MeSH
• flavonoidy farmakologie   chemie   izolace a purifikace   MeSH
• molekulární struktura MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• ovoce chemie   MeSH
• pikráty farmakologie   MeSH
• Scrophulariaceae chemie   MeSH
• Geografické názvy
• Česká republika MeSH

ETHNOPHARMACOLOGICAL RELEVANCE: Paulownia tomentosa Steud. (P. tomentosa) is a medium-sized tree traditionally used in Chinese folk medicine for the treatment of infectious diseases. It is a rich source of prenylated phenolic compounds that have been extensively studied for their promising biological activities. AIM OF THE STUDY: Due to the increasing development of antibiotic resistance, our study investigated plant-derived natural products from the fruits of P. tomentosa that could control Staphylococcus aureus infections with novel targets/modes of action and reduce antimicrobial resistance. MATERIALS AND METHODS: The ethanolic extract was fractionated and detected by liquid chromatography. The antistaphylococcal effects of the plant formulations were studied in detail in vitro by various biological methods, including microdilution methods for minimum inhibitory concentration (MIC), the checkerboard titration technique for synergy assay, fluorescence measurements for membrane disruption experiments, autoinducer-2-mediated bioassay for quorum sensing inhibition, and counting of colony-forming units for relative adhesion. Morphology was examined by transmission electron microscopy. RESULTS: Total ethanolic extract and chloroform fraction showed MICs of 128 and 32 μg/mL, respectively. Diplacol, diplacone, and 3'-O-methyl-5'-hydroxydiplacone inhibited S. aureus growth in the range of 8-16 μg/mL. Synergistic potential was shown in combination with mupirocin and fusidic acid. The ethanolic extract and the chloroform fraction destroyed the cell membranes by 91.61% and 79.46%, respectively, while the pure compounds were less active. The ethanolic extract and the pure compounds reduced the number of adhered cells to 47.33-10.26% compared to the untreated control. All tested plant formulations, except diplacone, inhibited quorum sensing of S. aureus. Transmission electron microscopy showed deformation of S. aureus cells. CONCLUSIONS: The products from the fruit of P. tomentosa showed antimicrobial properties against S. aureus alone and in combination with antibiotics. By affecting intracellular targets, geranylated flavonoids proposed novel approaches in the control of staphylococcal infections.

• MeSH
• antibakteriální látky chemie   MeSH
• antiinfekční látky * farmakologie   MeSH
• chloroform MeSH
• ethanol farmakologie   MeSH
• hluchavkotvaré * MeSH
• mikrobiální testy citlivosti MeSH
• ovoce chemie   MeSH
• rostlinné extrakty chemie   MeSH
• stafylokokové infekce * MeSH
• Staphylococcus aureus MeSH
• Publikační typ
• časopisecké články MeSH

The newly discovered 5,7-dihydroxy-6-geranylchromone ( 1) was isolated from PAULOWNIA TOMENTOSA fruit and subsequently characterized. The structure of the isolated compound was elucidated on the basis of extensive NMR experiments including HMQC, HMBC, COSY, and NOESY, as well as HR-MS, IR, and UV. The cytotoxicity of 1 was evaluated using a plant cell model represented by tobacco BY-2 cells. The other phytoconstituents ( 2 - 8) previously isolated from P. TOMENTOSA were similarly evaluated together with the known flavanones 10 and 11. The cytotoxicity (human erythro-leukaemia cell line K562) and activity on erythroid differentiation of compounds 2 - 9 and 12 and 13 have also been evaluated. Acteoside ( 2) was determined to be the most toxic of the compounds tested on BY-2 cells, diplacone ( 6) on the K562 cell line. Some aspects of the relationship between the flavanone skeleton substitution and the metabolic activation necessary for a toxic effect are discussed.

• MeSH
• buněčná diferenciace účinky léků   MeSH
• buňky K562 MeSH
• chromony chemie   izolace a purifikace   toxicita   MeSH
• erytroidní buňky účinky léků   MeSH
• fenoly chemie   izolace a purifikace   toxicita   MeSH
• financování organizované MeSH
• flavanony chemie   izolace a purifikace   toxicita   MeSH
• LD50 MeSH
• lidé MeSH
• Magnoliopsida chemie   MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• ovoce chemie   MeSH
• tabák cytologie   účinky léků   MeSH
• Check Tag
• lidé MeSH