Effects of Frankincense Compounds on Infection,Inflammation, and Oral Health

Boswellia trees, found throughout the Middle East and parts of Africa and Asia, are the source of frankincense oil. Since antiquity, frankincense has been traded as a precious commodity, but it has also been used for the treatment of chronic disease, inflammation, oral health, and microbial infection. More recently, the bioactive components of Boswellia trees have been identified and characterized for their effects on cancer, microbial infection (especially infection by oral pathogens), and inflammation. Most studies have focused on cell lines, but more recent research has also investigated effects in animal models of disease. As natural products are considered to be safer than synthetic drugs, there is growing interest in further developing the use of substances such as frankincense oil for therapeutic treatment.     

Synthesis,Pharmacokinetic Characterization and Antioxidant Capacity of Carotenoid Succinates and Their Melatonin Conjugates

Carotenoid succinates were synthesized from hydroxy carotenoids and were coupled to a commercially available derivative of melatonin via amide bond for producing more powerful anti-oxidants and yet new hybrid lipophilic bifunctional molecules with additional therapeutic effects. The coupling reactions produced conjugates in acceptable to good yields. Succinylation increased the water solubility of the carotenoids, while the conjugation with melatonin resulted in more lipophilic derivatives. The conjugates showed self-assembly in aqueous medium and yielded relatively stable colloidal solutions in phosphate-buffered saline. Antioxidant behavior was measured with ABTS and the FRAP methods for the carotenoids, the carotenoid succinates, and the conjugates with melatonin. A strong dependence on the quality of the solvent was observed. TEAC values of the new derivatives in phosphate-buffered saline were found to be comparable to or higher than those of parent carotenoids, however, synergism was observed only in FRAP assays.     

Metabolic Profile of Agropyron repens (L.) P. Beauv. Rhizome Herbal Tea by HPLC-PDA-ESI-MS/MS Analysis

Agropyron repens (L.) P. Beauv. (couch grass) is a world-wide infesting rhizomatous plant with pharmacological applications. Chemical research is focused on its allelopathic and anti-inflammatory components, which are mainly present in the essential oil. Conversely, the aqueous extracts have been sparingly investigated, although the herbal tea is by far the most used formulation. To fill the gap, the metabolic profile of Agropyron repens rhizome herbal tea was investigated by electrospray ionization (ESI) tandem–mass spectrometry (MS/MS); the phenolic profile was investigated by HPLC-PDA-ESI-MS/MS. ESI-MS fingerprinting was provided, evidencing diagnostic ions for saccharides, organic acids and amino acids. The HPLC-PDA-ESI-MS/MS analysis evidenced at least 20 characteristic phenolic compounds, the most representative being caffeoyl and feruloyl quinic esters, followed by coumaric, caffeic and ferulic acids, and hesperidin among flavonoids. In addition, the essential amino acid tryptophan was identified for the first time. The results suggest new perspectives of applications for Agropyron repens rhizome.     

Epilobium angustifolium L. as a Potential Herbal Component of Topical Products for Skin Care and Treatment—A Review

Epilobium angustifolium L. (EA) has been used as a topical agent since ancient times. There has been an increasing interest in applying EA as a raw material used topically in recent years. However, in the literature, there are not many reports on the comprehensive application of this plant to skin care and treatment. EA contains many valuable secondary metabolites, which determine antioxidant, anti-inflammatory, anti-aging, and antiproliferative activity effects. One of the most important active compounds found in EA is oenothein B (OeB), which increases the level of ROS and protects cells from oxidative damage. OeB also influences wound healing and reduces inflammation by strongly inhibiting hyaluronidase enzymes and inhibiting COX-1 and COX-2 cyclooxygenases. Other compounds that play a key role in the context of application to the skin are flavonoids, which inhibit collagenase and hyaluronidase enzymes, showing anti-aging and anti-inflammatory properties. While terpenes in EA play an important role in fighting bacterial skin infections, causing, among other things cell membrane, permeability increase as well as the modification of the lipid profiles and the alteration of the adhesion of the pathogen to the animal cells. The available scientific information on the biological potential of natural compounds can be the basis for the wider use of EA in skin care and treatment. The aim of the article is to review the existing literature on the dermocosmetic use of E. angustifolium.     

Low-Molecular Pyrazine-Based DNA Binders: Physicochemical and Antimicrobial Properties

Pyrazine and its derivatives are a large group of compounds that exhibit broad biological activity, the changes of which can be easily detected by a substituent effect or a change in the functional group. The present studies combined theoretical research with the density functional theory (DFT) approach (B3LYP/6-311+G**) and experimental (potentiometric and spectrophotometric) analysis for a thorough understanding of the structure of chlorohydrazinopyrazine, its physicochemical and cytotoxic properties, and the site and nature of interaction with DNA. The obtained results indicated that 2-chloro-3-hydrazinopyrazine (2Cl3HP) displayed the highest affinity to DNA. Cytotoxicity studies revealed that the compound did not exhibit toxicity toward human dermal keratinocytes, which supported the potential application of 2Cl3HP in clinical use. The study also attempted to establish the possible equilibria occurring in the aqueous solution and, using both theoretical and experimental methods, clearly showed the hydrophilic nature of the compound. The experimental and theoretical results of the study confirmed the quality of the compound, as well as the appropriateness of the selected set of methods for similar research.     

Trichoderma Enzymes for Degradation of Aflatoxin B1 and Ochratoxin A

The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites. This work evaluated the effect of exoenzymes produced by the beneficial fungus Trichoderma afroharzianum strain T22 in degrading Aflatoxin B1 (AFB1) and Ochratoxin A (OTA). The ability of Trichoderma to produce hydrolases was stimulated by using different inducing substrates. The highest AFB1 and OTA degradation activity was obtained using a medium containing lyophilized mushrooms and crude fiber. The T. afroharzianum T22’s ability to reduce mycotoxins may be attributed to peroxidase enzymes. This study showed that T. afroharzianum strain T22 or its peroxidase supplementation could represent a sustainable strategy for the degradation of AFB1 and OTA in feed and food products.     

Synthesis and Luminescent Properties of s-Tetrazine Derivatives Conjugated with the 4H-1,2,4-Triazole Ring

New derivatives obtained by the combination of unique 1,2,4,5-tetrazine and 4H-1,2,4-triazole rings have great application potential in many fields. Therefore, two synthetic few-step methodologies, which make use of commercially available 4-cyanobenzoic acid (method A) and ethyl diazoacetate (method B), were applied to produce two groups of the aforementioned heterocyclic conjugates. In both cases, the target compounds were obtained in various combinations, by introducing electron-donating or electron-withdrawing substituents into the terminal rings, together with aromatic or aliphatic substituents on the triazole nitrogen atom. Synthesis of such designed systems made it possible to analyze the influence of individual elements of the structure on the reaction course, as well as the absorption and emission properties. The structure of all products was confirmed by conventional spectroscopic methods, and their luminescent properties were also determined.     

Synthesis of Cobalt Bis(Dicarbollide)—Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).     

Harnessing Protein-Ligand Interaction Fingerprints to Predict New Scaffolds of RIPK1 Inhibitors

Necroptosis has emerged as an exciting target in oncological, inflammatory, neurodegenerative, and autoimmune diseases, in addition to acute ischemic injuries. It is known to play a role in innate immune response, as well as in antiviral cellular response. Here we devised a concerted in silico and experimental framework to identify novel RIPK1 inhibitors, a key necroptosis factor. We propose the first in silico model for the prediction of new RIPK1 inhibitor scaffolds by combining docking and machine learning methodologies. Through the data analysis of patterns in docking results, we derived two rules, where rule #1 consisted of a four-residue signature filter, and rule #2 consisted of a six-residue similarity filter based on docking calculations. These were used in consensus with a machine learning QSAR model from data collated from ChEMBL, the literature, in patents, and from PubChem data. The models allowed for good prediction of actives of >90, 92, and 96.4% precision, respectively. As a proof-of-concept, we selected 50 compounds from the ChemBridge database, using a consensus of both molecular docking and machine learning methods, and tested them in a phenotypic necroptosis assay and a biochemical RIPK1 inhibition assay. A total of 7 of the 47 tested compounds demonstrated around 20–25% inhibition of RIPK1’s kinase activity but, more importantly, these compounds were discovered to occupy new areas of chemical space. Although no strong actives were found, they could be candidates for further optimization, particularly because they have new scaffolds. In conclusion, this screening method may prove valuable for future screening efforts as it allows for the exploration of new areas of the chemical space in a very fast and inexpensive manner, therefore providing efficient starting points amenable to further hit-optimization campaigns.