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.

• Keywords
• PPARγ, diabetes mellitus, hypoglycemic, natural products, plant phenolics,
• MeSH
• Phenols * chemistry   pharmacology   isolation & purification   MeSH
• Hypoglycemic Agents * chemistry   pharmacology   isolation & purification   MeSH
• Chick Embryo MeSH
• Humans MeSH
• Morus * chemistry   MeSH
• Mice MeSH
• PPAR gamma * agonists   metabolism   genetics   chemistry   MeSH
• Glucose Transporter Type 4 metabolism   genetics   MeSH
• Plant Extracts * chemistry   pharmacology   isolation & purification   MeSH
• Molecular Docking Simulation MeSH
• Animals MeSH
• Check Tag
• Chick Embryo MeSH
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phenols * MeSH
• Hypoglycemic Agents * MeSH
• PPAR gamma * MeSH
• Glucose Transporter Type 4 MeSH
• Plant Extracts * 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.

• Keywords
• MRSA, S. aureus, anti-inflammatory, antibacterial, antioxidant, cytotoxicity, mastitis, nanotechnology, prenylated flavonoids, skin, wound healing,
• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Anti-Infective Agents * pharmacology   MeSH
• Antioxidants * pharmacology   MeSH
• Flavonoids pharmacology   MeSH
• Wound Healing MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Anti-Infective Agents * MeSH
• Antioxidants * MeSH
• Flavonoids MeSH

2-arylbenzofurans represent a small group of bioactive compounds found in the plant family Moraceae. As it has not been investigated whether these substances are stable during passage through the gastrointestinal tract, their biological effects may be altered by the metabolism of intestinal microbiota or cells. The aim of the present study was to investigate and compare mulberrofuran Y (1), moracin C (2), and mulberrofuran G (3) in an in vitro model of human intestinal bacterial fermentation and in an epithelial model using the Caco-2 cell line. The analysis of compounds by LC-MS-Q-TOF showed sufficient stability in the fermentation model, with no bacterial metabolites detected. However, great differences in the quantity of permeation were observed in the permeability assay. Moreover, mulberrofuran Y (1) and moracin C (2) were observed to be transformed into polar metabolites by conjugation. Among the test compounds, mulberrofuran Y (1) was mostly stable and accumulated in endothelial cells (85.3%) compared with mulberrofuran G (3) and moracin C (2) (14% and 8.2%, respectively). Thus, only a small amount of mulberrofuran Y (1) was conjugated. Moracin C (2) and mulberrofuran G (3) were metabolized almost completely, with only traces of the unchanged molecule being found on the apical and cellular sides of the system. Only conjugates of mulberrofuran Y (1) and moracin C (2) were able to reach the basolateral side. Our results provide the basic description of bioavailability of these three compounds, which is a necessary characteristic for final evaluation of bio-efficacy.

• Keywords
• Caco-2 cells, LC-MS-Q-TOF, intestinal fermentation, moracin C, mulberrofuran G, mulberrofuran Y, permeability assay,
• Publication type
• Journal Article 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.

• Keywords
• CAA, Nrf2-ARE, antioxidants, catalase, glucose toxicity, plant phenolics, superoxide dismutase,
• MeSH
• Antioxidant Response Elements MeSH
• Antioxidants chemistry   pharmacology   MeSH
• Biomarkers MeSH
• Gene Expression MeSH
• NF-E2-Related Factor 2 genetics   metabolism   MeSH
• Phenols chemistry   pharmacology   MeSH
• Glucose MeSH
• Humans MeSH
• Molecular Structure MeSH
• Oxidative Stress MeSH
• Antineoplastic Agents chemistry   pharmacology   MeSH
• Plant Extracts chemistry   pharmacology   MeSH
• Superoxide Dismutase-1 genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• Biomarkers MeSH
• NF-E2-Related Factor 2 MeSH
• Phenols MeSH
• Glucose MeSH
• NFE2L2 protein, human MeSH Browser
• Antineoplastic Agents MeSH
• Plant Extracts MeSH
• SOD1 protein, human MeSH Browser
• Superoxide Dismutase-1 MeSH

Morusin is a prenylated flavonoid isolated from the root bark of Morus alba. Many studies have shown the ability of flavonoids to act as anti-inflammatory agents. The aim of this study was to evaluate the effect of morusin on experimentally colitis induced by 2,4,6-trinitrobenzensulfonic acid in Wistar rats and to compare it with sulfasalazine, a drug conventionally used in the treatment of inflammatory bowel disease. Morusin was administered by gavage at doses of 12.5, 25, or 50 mg/kg/day for five days. The colonic tissue was evaluated macroscopically, histologically, and by performing immunodetection and zymographic analysis to determine the levels of antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], interleukin (IL)-1β, and transforming growth factor (TGF)-β1 and the activities of matrix metalloproteinases (MMP) 2 and 9. The tissue damage scores were significantly reduced with increasing dose of morusin, however efficacy was not demonstrated at the highest dose. At the dose of 12.5 mg/kg, morusin exerted therapeutic effectivity similar to that of sulfasalazine (50 mg/kg). This was associated with significant reduction of TGF-β1 levels and MMP2 and MMP9 activities, and slight reduction of IL-1β. Our results suggest that morusin possesses therapeutic potential for the treatment of chronic inflammatory diseases.

• MeSH
• Flavonoids pharmacology   MeSH
• Colitis chemically induced   enzymology   prevention & control   MeSH
• Colon drug effects   enzymology   pathology   MeSH
• Trinitrobenzenesulfonic Acid MeSH
• Matrix Metalloproteinase 2 metabolism   MeSH
• Rats, Wistar MeSH
• Prenylation MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Flavonoids MeSH
• Trinitrobenzenesulfonic Acid MeSH
• Matrix Metalloproteinase 2 MeSH
• Mmp2 protein, rat MeSH Browser
• morusin MeSH Browser

This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened against Mycobacterium avium subsp. paratuberculosis CIT03, M. smegmatis ATCC 700084, M. kansasii DSM 44162, M. marinum CAMP 5644, Staphylococcus aureus ATCC 29213, methicillin-resistant S. aureus 63718, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Candida albicans CCM 8261, C. parapsilosis CCM 8260 and C. krusei CCM 8271, respectively, by standardized microdilution methods. The eventual antiproliferative (cytotoxic) impact of those compounds was examined on a human monocytic leukemia THP-1 cell line, as a part of the biological study. Promising potential against M. kansasii was found for 1-[3-(3-ethoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride (MIC = 31.75 μM), which was comparable to the activity of isoniazid (INH; MIC = 29.17 μM). Moreover, 1-{2-hydroxy-3-(3-methoxyphenylcarbamoyl)oxy)propyl}-4-(4-fluorophenyl)piperazin-1-ium chloride was even more effective (MIC = 17.62 μM) against given mycobacterium. Among the tested N-arylpiperazines, 1-{2-hydroxy-3-(4-methoxyphenylcarbamoyl)oxy)propyl}-4-(3-trifluorometh-ylphenyl)piperazin-1-ium chloride was the most efficient against M. marinum (MIC = 65.32 μM). One of the common features of all investigated substances was their insignificant antiproliferative (i.e., non-cytotoxic) effect. The study discussed structure-antimicrobial activity relationships considering electronic, steric and lipophilic properties.

• Keywords
• Mycobacterium kansasii, Mycobacterium marinum, N-arylpiperazines, electronic properties, lipophilicity, structure–activity,
• Publication type
• Journal Article MeSH