Bryophyte extracts as immunomodulators

Briofite (mahovine, jetrenjače i rožnjače) predstavljaju drugu najveću grupu kopnenih biljaka posle cvetnica, sa više od 20 000 vrsta rasprostranjenih širom sveta. Iako se od davnina koriste u tradicionalnoj medicini, tek je u skorije vreme počelo intenzivnije istraživanje njihovog hemijskog sastava, kao i potencijalnih bioloških aktivnosti. Među mnogobrojnim aktivnim komponentama briofita, polifenoli i triterpeni predstavljaju najvažnije grupe jedinjenja, koja su ujedno i nosioci njihove biološke aktivnosti. Antioksidativni, anti-inflamatorni, antitumorski, antineurodegenerativni, antimikrobni, antidijabetični i proregenerativni potencijal ekstrakata različitih briofita dokazan je u velikom broju studija. Ovaj pregledni rad ima za cilj da predstavi najnovija istraživanja o hemijskom sastavu i biološkimaktivnostima ekstrakata briofita sa posebnim osvrtom na mahovine Hypnum cupressiforme i Hedwigia ciliata i njihovoj potencijalnoj upotrebi kao imunomodulatora u prevenciji i/ili terapiji različitih bolesti čoveka.Bryophytes (mosses, liverworts, and hornworts) are the second largest group of land plants after flowering plants, with more than 20,000 species distributed worldwide. Although they have been used in traditional medicine since ancient times, their chemical composition and potential biological activities have only recently begun to be studied more intensively. Among the numerous bioactive constituents of moss plants, polyphenols and triterpenes represent the most important groups of compounds, which are also carriers of their biological activity. The antioxidant, anti-inflammatory, antitumor, antineurodegenerative, antimicrobial, antidiabetic, and proregenerative potential of various moss extracts have been confirmed in a large number of studies. This review presents the latest research on the chemical composition and biological activity of bryophyte extracts with special reference to the mosses Hypnum cupressiforme and Hedwigia ciliata and their potential use as immunomodulators in the prevention and/or therapy of various human diseases

Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury.

Peripheral nerve injury (PNI) leads to a series of cellular and molecular events necessary for axon regeneration and reinnervation of target tissues, among which inflammation is crucial for the orchestration of all these processes. Macrophage activation underlies the pathogenesis of PNI and is characterized by morphological/phenotype transformation from proinflammatory (M1) to an anti-inflammatory (M2) type with different functions in the inflammatory and reparative process. The aim of this study was to evaluate influence of the vitamin B (B1, B2, B3, B5, B6, and B12) complex on the process of neuroinflammation that is in part regulated by l-type CaV1.2 calcium channels. A controlled transection of the motor branch of the femoral peripheral nerve was used as an experimental model. Animals were sacrificed after 1, 3, 7, and 14 injections of vitamin B complex. Isolated nerves were used for immunofluorescence analysis. Treatment with vitamin B complex decreased expression of proinflammatory and increased expression of anti-inflammatory cytokines, thus contributing to the resolution of neuroinflammation. In parallel, B vitamins decreased the number of M1 macrophages that expressed the CaV1.2 channel, and increased the number of M2 macrophages that expressed this channel, suggesting their role in M1/M2 transition after PNI. In conclusion, B vitamins had the potential for treatment of neuroinflammation and neuroregeneration and thereby might be an effective therapy for PNI in humans

Crosstalk between vitamin status and gut microbiota: The key to maintaining immune homeostasis in the gut

The human gut microbiota is a diverse ecosystem that harbours a variety of microorganisms, including proteobacteria, bacteria, viruses, fungi, protists, and archaea. These microorganisms are collectively involved in several vital functions, including nutrient metabolism, vitamin synthesis, immune system regulation, neurotransmitter production, drug metabolism, and communication with the central nervous system. Dysbiosis within the gut microbiota has been shown to be a critical factor in the development of chronic disease. Investigating the effects of gut microbiota composition on overall health holds promise for the treatment of inflammatory diseases and the development of new therapeutic interventions. One notable aspect of the functionality of the gut microbiota is its involvement in the production of essential B vitamins. These vitamins exert a significant influence on immune responses and the composition of the gut microbiota. Competition may occur between the host and the gut microbiota for B vitamins, which some bacteria obtain from food or from synthesis by other gut bacteria. Thus, the availability of B vitamins in the diet has the potential to influence the composition of the gut microbiota and thus immune homeostasis. The profile of the gut microbiota varies individually, with diet proving to be an important modulator of both its composition and functional properties. However, further extensive research efforts are needed to understand the complex interplay between the gut microbiota, vitamins, and immune response mechanisms. Such investigations have the potential to develop innovative therapeutic strategies for a spectrum of inflammatory diseases, opening new avenues for improved patient outcomes

Antiproliferative and antimigratory effects of 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives in human breast cancer cells

In this study, a series of synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives as a potential antiproliferative and antimigratory agents were investigated. The possible antitumor mechanisms of investigated hydantoin derivatives were examined on human breast cancer cell line MDA-MB-231. The cells were treated with different concentrations of compounds (from 0.01 mu M to 100 mu M) during 24 h and 72 h. The proliferation index, nitric oxide production, apoptosis rate, and migration capacity were measured. The cell invasion potential was examined by measuring the level of MMP-9 and COX-2 gene expression. All tested compounds expressed antiproliferative activity and induced dose- and time-dependent increase in the level of nitrites. The investigated molecules significantly decreased cell survival rate, migration capacity and the expression levels of genes included in the process of tumor invasion. Obtained data suggest that the tested hydantoin derivatives express considerable antitumor activity by reducing cell division rate, elevating apoptosis level, and inhibiting the motility and invasiveness of breast cancer cells. The results obtained in this study indicate that investigated compounds express potential as a novel chemotherapeutic agents against breast cancer growth and progression. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University

Raman spectral analysis of the brainstem and responses of neuroglia and cytokines in whole-body gamma-irradiated rats after administration of aminothiol-based radioprotector GL2011

The search for an effective and non-toxic radioprotector is ongoing. We tested a novel, natural aminothiol-based radioprotector, GL2011, that was applied 30 min, 3 h or 6 h after the exposure of male albino Wistar rats to a 6.7 Gy mild dose of gamma radiation. The molecular signatures of radioprotection were investigated with Raman microspectroscopy of brainstem tissue samples. Morphological changes and activation of astrocytes and microglia were assessed by immunohistochemistry. Global markers of neuroinflammation were followed by ELISA to monitor blood plasma levels of proinflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines. A thirty-day follow-up determined survival of unprotected animals 37.5%. A survival increase was observed after radioprotection (75%, irrespective of the time of application). Raman spectra revealed a slightly deleterious effect of radiation on nucleic acids in surviving animals that was mitigated with the radioprotector, as GL2011 preserved the morphology of both astrocytes and microglia, with reduced microglial infiltration. Cytokine assessment revealed an immunomodulatory effect of the novel radioprotector. The overall results point out the positive effects of a single dose of GL2011 applied at different times. The molecular and cellular changes in the brainstem indicate that the radioprotector applied after radiation conferred better protection, which underlines its translation to cure radiation accidents

Antitumor activity of Lamiaceae plants frequently used in Serbian folk medicine and cuisine.

Recently, cancer research has focused on searching for new and more effective antitumor agents of natural origin that can activate multiple defence mechanisms and selectively damage transformed cells. The goal of this research was to assess different antitumor mechanisms of ethanolic extracts of 18 Lamiaceae species traditionally used in Serbian folk medicine and cuisine, as well as their genotoxic potential towards HCT-116 (colorectal cancer) cells. The viability of treated HCT-116 cells was assessed by MTT assay; the production of reactive oxygen species (ROS) by treated HCT- 116 cells was determined using NBT assay, while their production of nitric oxide (NO) was evaluated using Griess assay. The genotoxic activity of the extracts on HCT-116 cells was tested in Comet assay, using etoposide as a positive control. The results indicated that lavender, basil, and rosemary inhibited the proliferation of these cells, significantly lowering their viability. Moreover, lavender and thyme extracts displayed a significant increase in ROS production, whereas ground- ivy, hyssop, lemon balm, peppermint, basil, rosemary, sage, and winter savory have significantly lowered their production. The results of the Griess assay suggested that lavender, motherwort, peppermint, basil, rosemary, sage, winter savory, ironwort, and thyme have significantly increased the production of NO. Furthermore, Comet assay results pointed out that motherwort, peppermint, basil, oregano, marjoram, winter savory, ironwort, wild thyme, thyme, and mountain germander possess genotoxic potential towards HCT-116 cells, while only basil had genotoxic activity statistically similar to etoposide. The obtained results are in accordance with our previous findings, which indicated that these extracts have antigenotoxic and genoprotective activities towards normal cells. Finally, it can be concluded that these traditionally valued plants might act as potent antitumor agents by modulating the proliferation and production of ROS and NO by cancer cells, as well as by expressing significant genotoxic properties towards cancer cells

Role of the bifurcated intramolecular hydrogen bond on the physicochemical profile of the novel azo pyridone dyes

A series of novel 5-(4-substituted phenylazo)-1-carboxymethyl-3-cyano-6-hydroxy-4-methyl-2-pyridones had been synthesized and characterized. The study includes spectral determination of the possible tautomeric forms and the intramolecular hydrogen bonding pattern. The influence of the bifurcated intramolecular hydrogen bond on the spectral properties has been discussed. The dyes exist in hydrazone form both solid state and in most of the employed solvents. Equilibrium between hydrazone and anion forms has been studied in N,N-dimethylformamide and N,N-dimethylacetamide. For quantitative elucidation of solvent effects on UV-Vis absorption maxima, a linear solvation energy relationship concept has been employed using Kamlet-Taft's and Catalan's equations. Antioxidative activity of the synthesized dyes has been chemically tested and two derivatives (hydroxy and methoxy) are qualified as promising antioxidant molecules

Synthesis, solvatochromism, and biological activity of novel azo dyes bearing 2-pyridone and benzimidazole moieties

New azo dyes bearing 2-pyridone and benzimidazole moieties were prepared using diazotization of 4-(1H-benzo[d]imidazol-2-yl)aniline and coupling of the obtained diazonium salt with substituted 3-cyano-2-pyridones. Obtained compounds were characterized via UV-Vis, FT-IR, and H-1 and C-13 NMR spectroscopy as well as by elemental analysis data. The UV-Vis spectra of the synthesized dyes were measured in thirteen solvents of different properties at room temperature. Solvatochromism and tautomerism of novel azo dyes were discussed. An MTT (3,4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test was performed to prove the biocompatibility of the investigated dyes. The investigated dyes exhibited satisfying antiproliferative activities against both tumor cell lines, MDA-MB-231 and HCT-116, demonstrating the potent capacity for treatment of tumors

Biocompatible and degradable scaffolds based on 2-hydroxyethyl methacrylate, gelatin and poly(beta amino ester) crosslinkers

Gelatin hydrogels have great potential in regenerative medicine but their weak mechanical properties are a major drawback for the load-bearing applications, such as scaffolds for tissue engineering. To overcome this deficiency, novel biodegradable hydrogels with improved mechanical properties were prepared by combining gelatine with 2-hydroxyethyl methacrylate (HEMA), using a double network synthetic procedure. The first, superporous and mechanically strong network, was obtained by free radical polymerization of HEMA at cryogenic temperature, in the presence of gelatin. Degradable poly (beta-amino ester) (PBAE) macromers of different chemical composition or molecular weight were used as crosslinkers to introduce hydrolytically labile bonds in PHEMA. The second gelatin network was formed by crosslinking gelatin with glutaraldehyde. For comparison, a set of biodegradable PHEMA networks was obtained by polymerization of HEMA at cryogenic temperature. All samples were characterized revealing that mechanical strength, swelling behavior and degradation rate as well as high biocompatibility of new IPNs are in accordance with values required for scaffolds in tissue engineering applications and that tuning of these properties is accomplished by simply using different PBAE macromers