Selenoneine-inspired selenohydantoins with glutathione peroxidase-like activity.

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF3) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases.

Phytochemical profiling, antioxidant potential and protective effect of leaves extract of tunisian Vitis vinifera autochthonous accessions against acute CCl4-injured hepatotoxicity in mice.

Vitis vinifera leaves (VVL) are agro-industrial waste. In the current study, the phytochemical profile of V. vinifera leaves extracts (VVLE) of two Tunisian autochthonous accessions was determined via LC-UV-ESI/MS, and their antioxidant and hepatoprotective properties were also assessed. Mice were pretreated orally with VVLE (7.5, 15 and 30 mg/kg) for 7 days, and then received acutely and by i.p. a solution CCl4 at 12% in sunflower oil (v/v). Serum levels of hepatic markers, oxidative stress indicators in liver tissue and histological changes were assessed. LC-UV-ESI/MS analysis revealed four phenolic compounds identified in both extracts with quercetin-3-O-glucuronide being the dominant constituent (23.32 ± 1.06 vs. 10.24 ± 0.12 mg/g DM, p < 0.05 for wild and cultivated accessions, respectively). The Antioxidant activity revealed a significant difference between the genotypes. Moreover, the VVLE of the wild "Nefza-I" ecotype was the most active based on antioxidant assays. Furthermore, the results showed that pre-treatment, especially with VVLE, of the wild ecotype "Nefza-I", attenuated CCl4-induced acute liver injury in a dose-dependent manner, as demonstrated by the decrease in the activities of hepatic serum function markers. This was also evidenced by a decrease in the levels of lipoperoxidation and histological damage in the liver, as well as a restoration of antioxidant enzyme activities (SOD and catalase) and an increase in the hepatic glutathione content. Our results demonstrate that VVLE possesses protective effects on CCl4-induced liver injury. Overall, the wild ecotype "Nefza-I" extract could serve as an effective protector against CCl4-induced hepatocellular oxidative stress.

New Pregnane Glycosides Isolated from Caralluma hexagona Lavranos as Inhibitors of α-Glucosidase, Pancreatic Lipase, and Advanced Glycation End Products Formation.

Caralluma hexagona Lavranos (Family Asclepiadaceae) is an endemic herb in Yemen and Saudi Arabia, traditionally used to treat diabetes, abdominal pain, and stomach ulcers. Different extracts, fractions, and main constituents of C. hexagona were evaluated for their inhibitory activity against key enzymes in diabetes and hyperlipidemia, i.e., α-glucosidase and pancreatic lipase. In addition, the antioxidative effect and inhibition of advanced glycation end products (AGEs) were also assayed. Using a bioguided approach, the crude aqueous, methanolic extracts, methylene chloride (CH2Cl2), Diaion HP20 50% MeOH (DCF-1), and 100% MeOH (DCF-2) fractions of C. hexagona were evaluated for their possible α-glucosidase and pancreatic lipase inhibition and antioxidant activity. In addition, inhibition of AGE generation using bovine serum albumin (BSA)-fructose, BSA-methylglyoxal, and arginine-methylglyoxal models was carried out. Moreover, the main constituents of the most active fraction were isolated and identified using different chromatographic and sprectroscopic methods. From the most active CH2Cl2 fraction, four new pregnane glycosides were isolated and identified as 12ß-O-benzoyl 3ß,8ß,12ß,14ß,20-pentahydroxy-(20S)-pregn-5-ene-3-O-ß-d-glucopyranosyl-(1 → 4)-O-ß-d-digitaloside (1), 3ß,8ß,14ß,20-tetrahydroxy-(20S)-pregn-5-ene-3-O-ß-d-glucopyranosyl-(1 → 4)-O-ß-d-digitaloside-20-O-3-isoval-ß-d-glucopyranoside (2), 3ß,8ß,14ß,20-tetrahydroxy-(20R)-pregn-5-ene-3-O-ß-d-glucopyranosyl-(1 → 4)-O-ß-d-digitaloside-20-O-3-isoval-4-benzoyl-ß-d-glucopyranoside (3A), and 3ß,8ß,14ß,20-tetrahydroxy-(20R)-pregn-5-ene-3-O-ß-d-glucopyranosyl-(1 → 4)-O-ß-d-digitaloside-20-O-3,4 di-benzoyl-ß-d-glucopyranoside (3B). Among the tested samples, the highest trolox equivalent (TE) antioxidant capacity (TEAC) was observed for DCF-1 with values of 128.53 ± 5.07, 378.58 ± 5.19, and 106.71 ± 5.66 µM TE/mg using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant potential (FRAP) assays, respectively. The isolated apigenin-8-C-neohesperoside showed the highest antioxidant capacity (168.80 ± 1.80 and 278.21 ± 13.26 µM TE/mM) in DPPH and FRAP, respectively, while luteolin 4'-O-ß-d-neohesperidoside had the highest TEAC (599.19 ± 9.57 µM TE/mM) in ABTS assay. Compounds 1, 2, and the mixture 3A and 3B inhibited α-glucosidase with IC50 values of 0.92 ± 0.02, 0.67 ± 0.01, and 0.74 ± 0.02 mM, respectively. In the AGE assays, DCF-1 showed the highest inhibitory effect in BSA-fructose and arginine-methylglyoxal models with IC50 values of 0.39 ± 0.02 and 0.77 ± 0.10 mg/mL, respectively. Among the isolated compounds, flavonoid compounds showed the highest antiglycation effect, while pregnanes revealed higher α-glucosidase inhibition. In conclusion, the current study revealed that C. hexagona is a promising Yemeni natural remedy, of which the major content of pregnane glycosides and flavonoids could be considered as a new therapeutic candidate targeting the metabolic syndrome.

Elicitation of Antimicrobial Active Compounds by Streptomyces-Fungus Co-Cultures.

The bacteria of the genus Streptomyces and Basidiomycete fungi harbor many biosynthetic gene clusters (BGCs) that are at the origin of many bioactive molecules with medical or industrial interests. Nevertheless, most BGCs do not express in standard lab growth conditions, preventing the full metabolic potential of these organisms from being exploited. Because it generates biotic cues encountered during natural growth conditions, co-culture is a means to elicit such cryptic compounds. In this study, we explored 72 different Streptomyces-fungus interaction zones (SFIZs) generated during the co-culture of eight Streptomyces and nine fungi. Two SFIZs were selected because they showed an elicitation of anti-bacterial activity compared to mono-cultures. The study of these SFIZs showed that co-culture had a strong impact on the metabolic expression of each partner and enabled the expression of specific compounds. These results show that mimicking the biotic interactions present in this ecological niche is a promising avenue of research to explore the metabolic capacities of Streptomyces and fungi.

New approach in the characterization of bioactive compounds isolated from Calycotome spinosa (L.) Link leaves by the use of negative electrospray ionization LITMSn, LC-ESI-MS/MS, as well as NMR analysis.

Two novel compounds were isolated for the first time from Calycotome spinosa (L.) Link, an alkaloid 5-Hydroxy-1H-indole (4) and a cyclitol D-pinitol (5), together with the three well-known flavonoids; Chrysin-7-O-(ß-D-glucopyranoside) (1), Chrysin-7-O-ß-D-(6″-acetyl)glycopyranoside (2) and Apigenin-7-O-ß-D-glycopyranoside (3). The chemical structures of the isolated compounds were elucidated by spectroscopic data and mass spectrometric analyses; including a fresh approach 1D-NMR, 2D-NMR with LC-ESI-MS/MS. In this study, the new compound (4) that has been obtained from the leaves MeOH extract presented the best radical scavenging activity (DPPH) (IC50 < 10 µg/mL) compared to the standard butylated hydroxytoluene (BHT, IC50 = 34.73 ± 0.23 µg/mL) and showed the highest total antioxidant capacity (TAC = 985.54 ± 0.13 mg AAE/g extract) in contrast to ascorbic acid (TAC = 905.95 ± 0.07 mg AAE/g extract). Furthermore, the strongest reducing power (EC50 = 344.82 ± 0.02 µg/mL), as well as the remarkable scavenging potential by ABTS assay (IC50 = 7.8 ± 0.43 µg/mL), were exhibited by the same composite (4). Followed by the methanol crude extract and the compound (3) that also showed a potent antioxidant (DPPH; IC50 = 41.04 ± 0.15 and 47.36 ± 0.21 µg/mL, TAC; 671.02 ± 0.21 and 608.67 ± 0.34 mg AAE/g extract, FRAP; EC50 = 763.73 ± 0.32 and 814.61 ± 0.31 µg/mL, ABTS; IC50 = 19.18 ± 0.06 and 63.72 ± 0.64 µg/mL, respectively), but less than the previous samples. On the opposite side, compound (5) had the lowest activity, in which its values were less interesting to determine. Moreover, compound (4) has equally exerted an attractive antibacterial activity against Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC- 27853) and Salmonella abony (NCTC 6017), as measured by the disc diffusion assay, with inhibition zones of 16 ± 0.5, 9.83 ± 0.29 and 8 ± 0.28 mm, in that order. To the best of our knowledge, 5-Hydroxy-1H-indole was isolated from plants for the second time in our current work. Thus, the obtained results from this investigation propose that the leaves of C. spinosa are a rich natural source for value molecules as potential antioxidants and antimicrobial agents for best human health.

Optimisation of phytochemical characteristics and antioxidative properties of Foeniculum vulgare Mill. seeds and Ocimum basilicum L. leaves superfine powders using new parting process.

INTRODUCTION: Fennel (Foeniculum vulgare Mill.) and basil (Ocimum basilicum L.) are two aromatic medicinal plants. Recently, a new parting process which is named CDS "Comminution and to control Diffraction Sieving" is taken into consideration and its positive effect on the extraction of bioactive compounds from the plants, without any solvent, is reported. OBJECTIVE: Study the effect of CDS on phytochemical properties of superfine powders of fennel seeds and basil leaves. METHODS: Fennel seeds and basil leaves superfine powders were fractionated as follows: 100-180 µm, 180-315 µm, 315-500 µm, > 500 µm and unsieved superfine powders. Extraction of polyphenols was carried out using hydromethanolic maceration. The essential oils were extracted by maceration with dichloromethane. The antioxidant activities were evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Using liquid chromatography ultraviolet electrospray ionisation mass spectrometry (LC-UV-ESI-MS), concentrations of characterised phenolic compounds were measured. The essential oils compositions were characterised using gas chromatography mass spectrometry (GC-MS). RESULTS: In fennel seeds, the 100-180 µm fraction had maximum antioxidant activity and LC-UV-ESI-MS analyses proved that the best extraction of certain polyphenols was obtained in the 100-180 µm fraction. In basil leaves, the best antioxidant activity corresponded to the 315-500 µm fraction and LC-UV-ESI-MS analyses showed that the polyphenols were concentrated in the < 315 µm fractions. For both plants, GC-MS presented that the essential oils were concentrated in the 315-500 µm fraction. CONCLUSION: CDS as a new green parting process leads to improve the phytochemical properties of these two superfine plant powders in the specific granulometric classes.

Effect of particle size on antioxidant activity and catechin content of green tea powders.

This work evaluated the effect of grinding and sieving process of green tea leaves on particle size distribution and antioxidant activity. Granulometric classes ranging from 20 µm to 500 µm were studied. Hydroalcoholic extracts of green tea powders (GTPs) were analysed for total phenolic, total flavonoid, and catechin contents. The fraction of 100-180 µm ground at 6000 rpm showed the maximum catechin content with 33.5 mg/g dry matter (DM) and, the best antioxidant activity with IC50 values of 0.28 µg/mL and 0.13 µg/mL using DPPH and ABTS radical scavenging assays, respectively. However, antioxidant properties and catechin content decreased for particle of sizes less than 50 µm. Catechin content was higher for those ground at 6000 rpm as compared to at 18,000 rpm. The best grinding conditions and particle size were 6000 rpm and 100-180 µm.