The aim of our study was to determine the PPARγ agonism and hypoglycemic activity of natural phenolics isolated from Paulownia tomentosa and Morus alba. We started with a molecular docking preselection, followed by in vitro cell culture assays, such as PPARγ luciferase reporter gene assay and PPARγ protein expression by Western blot analysis. The ability of the selected compounds to induce GLUT4 translocation in cell culture and lower blood glucose levels in chicken embryos was also determined. Among the thirty-six plant phenolic compounds, moracin M showed the highest hypoglycemic effect in an in ovo experiment (7.33 ± 2.37%), followed by mulberrofuran Y (3.84 ± 1.34%) and diplacone (3.69 ± 1.37%). Neither moracin M nor mulberrofuran Y showed a clear effect on the enhancement of GLUT4 translocation or agonism on PPARγ, while diplacone succeeded in both (3.62 ± 0.16% and 2.4-fold ± 0.2, respectively). Thus, we believe that the compounds moracin M, mulberrofuran Y, and diplacone are suitable for further experiments to elucidate their mechanisms of action.

• Klíčová slova
• PPARγ, diabetes mellitus, hypoglycemic, natural products, plant phenolics,
• MeSH
• fenoly * chemie   farmakologie   izolace a purifikace   MeSH
• hypoglykemika * chemie   farmakologie   izolace a purifikace   MeSH
• kuřecí embryo MeSH
• lidé MeSH
• Morus * chemie   MeSH
• myši MeSH
• PPAR gama * agonisté   metabolismus   genetika   chemie   MeSH
• přenašeč glukosy typ 4 metabolismus   genetika   MeSH
• rostlinné extrakty * chemie   farmakologie   izolace a purifikace   MeSH
• simulace molekulového dockingu MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fenoly * MeSH
• hypoglykemika * MeSH
• PPAR gama * MeSH
• přenašeč glukosy typ 4 MeSH
• rostlinné extrakty * MeSH

The review presents prenylated flavonoids as potential therapeutic agents for the treatment of topical skin infections and wounds, as they can restore the balance in the wound microenvironment. A thorough two-stage search of scientific papers published between 2000 and 2022 was conducted, with independent assessment of results by two reviewers. The main criteria were an MIC (minimum inhibitory concentration) of up to 32 µg/mL, a microdilution/macrodilution broth method according to CLSI (Clinical and Laboratory Standards Institute) or EUCAST (European Committee on Antimicrobial Susceptibility Testing), pathogens responsible for skin infections, and additional antioxidant, anti-inflammatory, and low cytotoxic effects. A total of 127 structurally diverse flavonoids showed promising antimicrobial activity against pathogens affecting wound healing, predominantly Staphylococcus aureus strains, but only artocarpin, diplacone, isobavachalcone, licochalcone A, sophoraflavanone G, and xanthohumol showed multiple activity, including antimicrobial, antioxidant, and anti-inflammatory along with low cytotoxicity important for wound healing. Although prenylated flavonoids appear to be promising in wound therapy of humans, and also animals, their activity was measured only in vitro and in vivo. Future studies are, therefore, needed to establish rational dosing according to MIC and MBC (minimum bactericidal concentration) values, test potential toxicity to human cells, measure healing kinetics, and consider formulation in smart drug release systems and/or delivery technologies to increase their bioavailability.

• Klíčová slova
• MRSA, S. aureus, anti-inflammatory, antibacterial, antioxidant, cytotoxicity, mastitis, nanotechnology, prenylated flavonoids, skin, wound healing,
• MeSH
• antibakteriální látky farmakologie   MeSH
• antiinfekční látky * farmakologie   MeSH
• antioxidancia * farmakologie   MeSH
• flavonoidy farmakologie   MeSH
• hojení ran MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• antiinfekční látky * MeSH
• antioxidancia * MeSH
• flavonoidy 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.

• Klíčová slova
• CAA, Nrf2-ARE, antioxidants, catalase, glucose toxicity, plant phenolics, superoxide dismutase,
• 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
• Názvy látek
• antioxidancia MeSH
• biologické markery MeSH
• faktor 2 související s NF-E2 MeSH
• fenoly MeSH
• glukosa MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• protinádorové látky MeSH
• rostlinné extrakty MeSH
• SOD1 protein, human MeSH Prohlížeč
• superoxiddismutasa 1 MeSH

Multidrug resistance (MDR) is a common problem when fighting cancer with chemotherapy. P-glycoprotein (P-gp, or MDR1) is an active pump responsible for the efflux of xenobiotics out of the cell, including anti-cancer drugs. It is a validated target against MDR. No crystal structure of the human P-gp is available to date, and only recently several cryo-EM structures have been solved. In this paper, we present a comprehensive computational approach that includes constructing the full-length three-dimensional structure of the human P-gp and its refinement using molecular dynamics. We assessed its flexibility and conformational diversity, compiling a dynamical ensemble that was used to dock a set of lignan compounds, previously reported as active P-gp inhibitors, and disclose their binding modes. Based on the statistical analysis of the docking results, we selected a system for performing the structure-based virtual screening of new potential P-gp inhibitors. We tested the method on a library of 87 natural flavonoids described in the literature, and 10 of those were experimentally assayed. The results reproduced the theoretical predictions only partially due to various possible factors. However, at least two of the predicted natural flavonoids were demonstrated to be effective P-gp inhibitors. They were able to increase the accumulation of doxorubicin inside the human promyelocytic leukemia HL60/MDR cells overexpressing P-gp and potentiate the antiproliferative activity of this anti-cancer drug.

• Klíčová slova
• P-glycoprotein, flavonoids, molecular docking, molecular dynamics, multidrug resistance, natural compounds, structure-based virtual screening,
• Publikační typ
• časopisecké články MeSH

Paulownia tomentosa, a member of the plant family Paulowniaceae and a rich source of biologically active secondary metabolites, is traditionally used in Chinese herbal medicine. Flavonoids, lignans, phenolic glycosides, quinones, terpenoids, glycerides, phenolic acids, and miscellaneous other compounds have been isolated from different parts of P. tomentosa plant. Recent interest in this species has focused on isolating and identifying of prenylated flavonoids, that exhibit potent antioxidant, antibacterial, and antiphlogistic activities and inhibit severe acute respiratory syndrome coronavirus papain-like protease. They show cytotoxic activity against various human cancer cell lines and inhibit the effects of human cholinesterase, butyrylcholinesterase, and bacterial neuraminidases. Most of the compounds considered here have never been isolated from any other species of plant. This review summarizes the information about the isolated compounds that are active, their bioactivities, and the structure-activity relationships that have been worked out for them.

• Klíčová slova
• Bignonia tomentosa, Flavonoid, Lignan, Paulownia tomentosa, Paulowniaceae, Phenolic glycosides,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

• MeSH
• cytoprotekce účinky léků   MeSH
• experimentální diabetes mellitus farmakoterapie   MeSH
• flavanony izolace a purifikace   farmakologie   MeSH
• myši MeSH
• ovoce chemie   MeSH
• scavengery volných radikálů izolace a purifikace   farmakologie   MeSH
• Scrophulariaceae chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• flavanony MeSH
• scavengery volných radikálů MeSH

Paulownia tomentosa is a large indecidous tree planted mostly for its fast growing wood and decorative purposes. The tree is also used in traditional Chinese medicine. As a part of our study of natural polyphenols, the fruits of Paulownia tomentosa were extracted by EtOH and than subjected to liquid/liquid extraction. Fractions were analysed by TLC and HPLC to determine presence of phenolic substances. We identified and quantified acteoside (1) and isoacteoside (2) in the EtOAc and n-BuOH extracts; mimulone (3) and diplacone (4) in the MeOH extract. To determine the antiradical activity of extracts we used the anti DPPH and peroxynitrite assays. The activity was expressed as Trolox C equivalents, IC50 for DPPH scavenging and a time dependency course was established. The polyphenols content was determined; results were expressed as gallic acid equivalents. Using these methods we found the fractions of the n-BuOH, EtOAc and MeOH extracts that display antiradical activity, which could be exploited as potential pharmaceuticals.

• MeSH
• fenoly izolace a purifikace   farmakologie   MeSH
• flavonoidy izolace a purifikace   farmakologie   MeSH
• léčivé rostliny MeSH
• léky rostlinné čínské izolace a purifikace   farmakologie   MeSH
• ovoce chemie   MeSH
• polyfenoly MeSH
• rozpouštědla MeSH
• scavengery volných radikálů izolace a purifikace   farmakologie   MeSH
• stromy MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenoly MeSH
• flavonoidy MeSH
• léky rostlinné čínské MeSH
• polyfenoly MeSH
• rozpouštědla MeSH
• scavengery volných radikálů MeSH