Anna Hering

Isomangiferin is a natural C-glycosylated xanthone, an isomer of mangiferin. The biological properties of isomangiferin are not clearly known. The antioxidant effect of this xanthone was assessed with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) tests. Isomangiferin’s cytoprotective effects against menadione in human keratinocytes HaCaT were evaluated via an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. Additionally, the inhibition of elastase and hyaluronidase by isomangiferin was tested spectrophotometrically. Antielastase activity was analyzed in silico and by evaluating the degradation of elastin fibers and elastin in tendons using image analysis. The results indicated that the antioxidant properties of the tested xanthone were stronger than those of ascorbic acid (the IC₅₀ values for isomangiferin and ascorbic acid were 27.04 ± 1.8 and 164.6 ± 3.29 µM; 9.57 ± 0.05 and 35.83 ± 0.45 µM; and 70.44 ± 1.4 and 315.85 ± 4.49 µM in ABTS, DPPH and FRAP tests, respectively). Isomangiferin at a concentration of 95 µM (40 µg/mL) effectively protected HaCaT cells from death. This compound also demonstrated a moderate ability to inhibit hyaluronidase activity. The ability to inhibit elastase was demonstrated via image analysis and supported by docking studies, which indicated that isomangiferin binds with elastase not directly within the catalytic site but in the S4 subpocket. This study shows a promising direction for the development of new agents that mitigate oxidative stress-induced aging by protecting both elastin fibers and hyaluronic acid from degradation.

Background/Objectives: Gastrointestinal cancers, including gastric and colon cancers, constitute a serious threat to global health due to their high incidence and limited treatment outcomes. Thus, natural products are becoming increasingly popular as potential chemopreventive agents. Coleus aromaticus Benth. is mainly used as a tasty addition to dishes and juices due to its aromatic and nutritional properties. The plant has many biological and pharmacological effects that require deeper evaluation. In this study, anticancer, antioxidant, and antimicrobial activities of ethanol, ethanol/water extracts, and juice from C. aromaticus leaves were evaluated. Methods: (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate)), molybdenum reducing power assay, and broth microdilution technique were used, respectively. Additionally, total phenolic (TPC) and total flavonoid content (TFC) with basic phytochemical composition of volatile compounds by GC-MS and GC-FID were assessed. Results: The results indicate that the strongest anticancer activity was provided by the ethanol extract with IC₅₀ values of 4.94 ± 0.48 and 24.99 ± 1.80 µg/mL on human gastric AGS cells and human colorectal HCT 116 cells, respectively. The antioxidant potential was also the highest for the ethanol extract with IC₅₀ values of 13.34 ± 0.11 (ABTS), 22.90 ± 1.30 (DPPH), and 290.17 ± 4.23 µg/mL (molybdenum reducing power). Antimicrobial experiments revealed that ethanol and ethanol/water extracts were the most potent on Clostridium perfringens (MIC value was C. aromaticus can be considered as a potential agent in the prevention and treatment of gastrointestinal cancers, especially the ethanol extract from the plant leaves due to its strong anticancer and antioxidant properties.

The skin is the largest organ of the body, and its proper care significantly influences the well-being of the entire organism. Therefore, the ingredients of cosmetics and dermocosmetics should inhibit processes leading to inflammation and degradation of skin macromolecules. To select the most promising Rubus caesius L. extract for use in cosmetic and dermocosmetic applications. Water and ethanol extracts from leaves and stems of Rubus caesius L. (European dewberry, Rosaceae) were tested for their antioxidant properties, protective effects against pathogenic bacterial strains and the influence on tyrosinase and collagenase activity. The most biologically active extracts were selected and analyzed using the HPLC method to estimate the content of major phenolic acids and their ability to penetrate into and through porcine skin from hydrogels. Ethanol extracts from Rubus caesius L. demonstrated significant biological activity, particularly in scavenging the ABTS radical and inhibiting tyrosinase and collagenase activity. Furthermore, ethanol extracts were effective against pathogenic bacteria, but not against commensal skin microbiota. Ethanol extracts from leaves and stems were rich in phenolic acids. The permeation experiment through porcine skin from hydrogels revealed that gallic acid and neochlorogenic acid from ethanol leaves extract exhibited the highest permeation capability. The ethanol extract demonstrated substantial activity in protecting the skin against pathogens, oxidative stress, and macromolecular degradation. The presence and transdermal permeability of phenolic acids were also confirmed. These findings highlight the high potential of Rubus caesius leaf ethanol extract for inclusion in cosmetic and dermocosmetic formulations.

Increased bacterial resistance to current antibiotics leads to a depletion of therapeutic options in medicine. One of the problems of current therapy is methicillin-resistant Staphylococcus aureus (MRSA), which, in addition to resistance to β-lactam antibiotics, is multidrug-resistant. Some strains can also produce biofilms, a multicellular structure that is resistant or tolerant to various antibiotics. In hospitals worldwide, about 15% of invasive infections are caused by MRSA. Extracts of Rubus caesius (dewberry) contain high concentrations of compounds such as phenolic acids, flavonoids, tannins, and anthocyanins, which have potential antibacterial properties. This study is the first to demonstrate the activity of aqueous and ethanolic extracts of dewberry leaves (L_H2O, L_EtOH) and stems (S_H2O, S_EtOH) against S. aureus and Staphylococcus epidermidis. The most active extracts were L_EtOH (MIC 0.16 ± 0.40–1.56 ± 0.23 mg/mL) and L_H2O (MIC 0.16 ± 0.20–10 mg/mL). The study showed that L_EtOH, S_EtOH and L_H2O extracts inhibited biofilm formation by clinical strains MRCN (methicillin-resistant coagulase-negative staphylococci) and MRSA (biofilm biomass reduction from 40 to 100%). Furthermore, 3,3′—dipropylthiacarbocyanine (DiSC₃(5)) and N-phenyl-naphthylamine (NPN) were used to show that L_EtOH and S_EtOH caused the membrane depolarization of the strains studied. We also showed that the extracts acted synergistically and additively with cefoxitin and amikacin, reducing the MIC values of the antibiotics used by 8- to 16-fold and of the extracts tested by 4- to 8-fold. This study provides new data on potential antibacterial drugs of therapeutic importance.

Background/Objectives: Recently, there has been great interest in metallopharmaceuticals as potential anticancer agents. In this context, presented studies aim to synthesize and evaluate of two copper(II) complexes derived from phthalazine- and imidazoline-based ligands against on three human cancer cell lines: cervix epithelial cell line (HeLa), breast epithelial-like adenocarcinoma (MCF-7), and triple–negative breast epithelial cancer cell line (MDA-MB-231), as well as non-tumorigenic cell line (HDFa). Moreover their antimicrobial, and antioxidant properties were assessed. Methods: The synthetized compounds—both free ligands L1, L2, L3 and copper(II) complexes C1 and C2—were characterized by elemental analysis, infrared spectroscopy. Additionally, a single-crystal X-ray diffraction studies we performed for free ligand L3 and its copper(II) complex C2. The stability of Cu(II)-complexes C1 and C2 was evaluated by UV-Vis spectroscopy. The cytotoxic potency of free ligands and their copper(II) complexes was estimated on HeLa, MCF-7, MDA-MB-231, as well as non-cancerous HDFa by use of an MTT assay after 48 h of incubation. Moreover, the antimicrobial activity of ligands L1 and L3 and their copper(II) complexes C1 and C2 was evaluated using reference strains of the following bacteria and yeasts: Staphylococcus aureus, Escherichia coli, and Candida albicans. The free radical scavenging properties of free ligands L1, L3 and the corresponding copper(II) complexes C1, C2 was tested with two colorimetric methods—ABTS, DPPH, and reduction ability assay (FRAP). Additionally, the ADME webtool was used to assess the drug-likeness of the synthesized compounds, as well as their physicochemical and pharmacokinetic properties. Results: Copper(II) complex C2 exhibited antitumor properties towards MDA-MB-231 compared with Cisplatin (cancer cell viability rate of 23.6% vs. 22.5%). At a concentration of 200 μg/mL, complexes C1 and C2 were less cytotoxic than the reference Cisplatin against a normal, non-cancerous skin fibroblast cell line (HDFa). According to in vitro tests, C2 reduced the viability of HeLa, MCF-7, and MDA-MB-231 cells by about 57.5–81.2%. It was evident that all compounds were devoid of antibacterial or antifungal activity. In vitro assays revealed that a moderate antiradical effect was observed for free ligand L1 containing phthalazin-1(2H)-imine in the ABTS radical scavenging assay (IC₅₀ = 23.63 µg/mL). Conclusions: The anticancer studies revealed that the most potent compound was copper(II) complex C2 bearing a phthalazin-1(2H)-one scaffold. None of the tested compounds showed antimicrobial or antifungal activity. This feature seems to be beneficial in terms of their potential uses as anticancer agents in the future. In vitro antiradical assays revealed that a moderate antioxidant effect was observed only for free ligand L1 containing phthalazin-1(2H)-imine.

Skin aging is accelerated by inflammation processes generated by oxidative stress and external factors such as UV radiation. Plants belonging to the genus Kalanchoe that are rich sources of antioxidants could potentially strengthen the skin barrier if used as ingredients in cosmetic formulations. However, their use is limited due to the contents of bufadienolides, known cardiotoxins. This study aimed to establish a semi-quantitative profile of bufadienolides in the juices of K. blossfeldiana, K. daigremontiana, and K. pinnata using UHPLC combined with charged aerosol detection (CAD) and high-resolution mass spectrometry (HR-MS). Additionally, the study determined the ability of bufadienolides to penetrate the skin barrier using the Bronaugh Diffusion Cell Apparatus and Strat-M membrane. The study also assessed the ferric and molybdenum-reducing powers, as well as the radical scavenging capabilities of these plants juices using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) methods. The in vitro antihyaluronidase and antityrosinase activities and sun protection factor (SPF) were evaluated spectrophotometrically, indicating moderate capability to inhibit the skin enzymes, but low SPF protection for all analyzed juices. The semi-qualitative analysis demonstrated the presence of bufadienolides occurring in two juices from K. daigremontiana and K. pinnata, with the highest contents of 1,3,5-bersaldegenin-orthoacetate, bryophyllin-A/bryotoxin-C, bersaldegenin-acetate/bryophyllin-C, and diagremontianin. After passing through the skin model, no bufadienolide compounds were present in the subcutaneous filtrate. Antiradical and reduction assays revealed the antioxidant potential of K. blossfeldiana and K. pinnata. These results indicate that Kalanchoe juices have antiaging potential and appear safe for dermal applications.

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine, linked to their remarkable medical properties. These species include Kalanchoe blossfeldiana succulents, which grow in tropical regions. Despite the great interest in this plant, there are no reports about its therapeutic effects on the skin. In this study, the antioxidant properties of K. blossfeldiana ethanol extracts and the skin permeation of a topical hydrogel containing the extract (HKB) were assessed. Additionally, the content of active compounds in the K. blossfeldiana extract was evaluated by UHPLC-MS and HPLC-UV. The extract was analyzed with three antioxidant assays: ABTS, DPPH, and FRAP. Furthermore, the antielastase and antihialuronidase properties of the tested extract were assessed. Ex vivo penetration studies were performed using the Franz diffusion cells. The estimation of the cytotoxicity of HKB was performed by using an MTT assay ((4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) on the human fibroblasts HFF-1. The results obtained show that the antioxidant properties of K. blossfeldiana extract were similar to those of ascorbic acid, while antielastase and antihialuronidase tests indicated the strong antiaging and anti-inflammatory activity of the extract (IC₅₀ was 26.8 ± 0.13 and 77.31 ± 2.44 µg/mL, respectively). Moreover, active ingredients contained in K. blossfeldiana extract penetrated through the human skin and accumulated in it. The cytotoxicity test showed that HKB had no significant effect on human fibroblasts at a concentration up to 0.5%. In conclusion, the hydrogel containing the K. blossfeldiana extract can be considered as an interesting and new alternative to dermatologic and cosmetic preparations.

Plant biotechnology creates opportunities for the cultivation of plants regardless of their natural habitats, which are often protected or difficult to access. Maintaining suspension cell cultures in bioreactors is an advanced part of biotechnological research that provides possibilities for obtaining plant tissue on a large scale. In this study, the suspension culture cultivation of a Chinese endemic plant, Schisandra henryi, in a stirred tank bioreactor was elaborated for the first time. The phytochemical profile of the tissue extracts was determined with UHPLC-MS/MS for the lignans (fifteen dibenzocyclooctadiene lignans, one aryltetralin lignan, and two neolignans) and UHPLC-DAD-ESI-MS³ for the phenolic compounds (procyanidins and their derivatives and catechin). The maximum total lignan content of 1289 µg/100 g DW was detected for the extracts from suspensions cultured in a bioreactor for over 10 days. For the phenolic compounds, catechin was the dominant compound (390.44 mg/100 g DW). The biological activity of the extracts was tested too. To determine antioxidant potential we used DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), Molybdenum reduction, and β-carotene bleaching tests. The inhibition activity of the S. henryi extract on the enzymes responsible for skin aging, hyaluronidase and tyrosinase, was assessed with spectrophotometry. The cytotoxic activity of the extracts was estimated on human ovarian SKOV-3, cervical HeLa, and gastric AGS cancer cells and non-cancer, normal fibroblasts by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The results showed the great potential of the obtained cell biomass extracts. The results of the antioxidant tests indicated their strong ability to reduce the level of free radicals, similarly to that of ascorbic acid, as well as the weak capacity to protect lipids from oxidation. Moreover, anticancer potential, particularly on the cervical and gastric cancer cells, was confirmed too.

A novel hybrid compound—2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (5) was synthesized and converted into di-substituted sulfonamide derivatives 6a–o and phthalazine ring opening products—hydrazonomethylbenzonitriles 7a–m. The newly prepared compounds were characterized using elemental analyses, IR and NMR spectroscopy, as well as mass spectrometry. Single crystal X-ray diffraction data were collected for the representative compounds 5, 6c, 6e, 7g, and 7k. The antiproliferative activity of compound 5, sulfonyl derivatives 6a–o and benzonitriles 7a–m was evaluated on approximately sixty cell lines within nine tumor-type subpanels, including leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast. None of the tested compounds showed any activity against the cancer cell lines used. The antioxidant properties of all compounds were assessed using the DPPH, ABTS, and FRAP radical scavenging methods, as well as the β-carotene bleaching test. Antiradical tests revealed that among the investigated compounds, a moderate ABTS antiradical effect was observed for sulfonamide 6j (IC₅₀ = 52.77 µg/mL). Benzonitrile 7i bearing two chlorine atoms on a phenyl ring system showed activity in a β-carotene bleaching test (IC₅₀ = 86.21 µg/mL). Finally, the interaction AGE/RAGE in the presence of the selected phthalazinimines 6a, 6b, 6g, 6m, and hydrazonomethylbenzonitriles 7a, 7c–g, and 7i–k was determined by ELISA assay. A moderate inhibitory potency toward RAGE was found for hydrazonomethylbenzonitriles—7d with an electron-donating methoxy group (R = 3-CH₃O-C₆H₄) and 7f, 7k with an electron-withdrawing substituent (7f, R = 2-Cl-C₆H₄; 7k, R = 4-NO₂-C₆H₄).

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine linked to their remarkable medical properties. One of them is Kalanchoe blossfeldiana succulents occurring in tropical regions. Despite the great interest in this plant, there are no reports about its therapeutic effects on the skin. In this study, the antioxidant properties and skin permeation of a topical hydrogel containing K. blossfeldiana ethanol extract was assessed. Additionally, the content of active compounds in the K. blossfeldiana extract was evaluated by UHPLC-MS and HPLC-UV. The extract was analysed with three antioxidant assays: ABTS, DPPH and FRAP. Furthermore, antielastase and antihialuronidase properties of the tested extract were assessed. The ex vivo penetration studies were performed using the Franz diffusion cells. The obtained results show that antioxidant properties of K. blossfeldiana extract were similar to ascorbic acid, while antielastase and antihialuronidase tests indicated strong antiaging and anti-inflammatory activity (IC50 was 26.8 ± 0.13 and 77.31 ± 2.44 µg/mL, respectively). Moreover, active ingredients contained in K. blossfeldiana extract penetrated through human skin and accumulate in it. In conclusion, the hydrogel containing K. blossfeldiana extract can be considered as an interesting and new alternative to dermatologic and cosmetic preparations.