Łukasz Marek

Reactive oxygen species (ROS) play a dual role in the human body; they are essential for normal cellular signaling but, when produced in excess, can disrupt metabolic processes and induce oxidative stress. The body relies on various defense mechanisms to neutralize ROS. Phenothiazine derivatives, due to their core tricyclic structure, are considered potential antioxidants. This study focused on evaluating the antioxidant capacity of perphenazine, a representative phenothiazine derivative, and comparing it to well-known antioxidants, Trolox and ascorbic acid. To achieve this, a series of spectrophotometric assays were performed: ABTS, DPPH, CUPRAC, FRAP, and superoxide anion (O2•−) scavenging. The results indicate that perphenazine shows significant antioxidant properties, particularly through its ability to reduce copper (Cu²⁺) and iron (Fe³⁺) ions and to scavenge ABTS•⁺ radicals. In contrast, its activity against DPPH• and superoxide anions was less pronounced. Relative antioxidant effectiveness, based on IC50 values, followed the order: CUPRAC > FRAP > ABTS > O2•− > DPPH. These findings suggest that perphenazine possesses selective antioxidant potential. Further studies on other phenothiazine derivatives are warranted to comprehensively assess their antioxidative potential.

Background/Objectives: Melanin synthesis in normal skin involves numerous genes, and disturbances in their function may increase the risk of malignant transformation of mela-nocytes. Genes regulating pheomelanin synthesis are of particular interest, as this pig-ment may actively contribute to cutaneous malignant melanoma pathogenesis. Normal melanocytes differ in pheomelanin content depending on skin phototype, which affects susceptibility to neoplastic transformation. However, the influence of pheomelanin on melanoma cell characteristics has not yet been fully elucidated. Methods: To gain further insight, we examined the expression of pheomelanogenesis-related genes in two mela-noma cell lines of distinct pigmentation status, amelanotic C32 and melanotic G361. We analysed the expression of 44 genes involved in melanocyte development and pigmenta-tion, classifying them by their direct or indirect role in pheomelanogenesis. Gene expres-sion levels were quantified using real-time reverse transcription polymerase chain reac-tion (real-time RT-PCR). Results: Our results show that melanoma cells with distinct pig-mentation phenotypes exhibit heterogeneous expression patterns. For instance, G361 cells expressed higher levels of POMC, MC1R, TYRP1, TYR, SLC45A2, and CTNS, while SLC7A11 and DCT/TYRP2 were more abundant in C32 cells. Conclusions: These findings suggest that differences in the expression of pheomelanin-related genes may contribute to melanoma cell diversity and could play a role in defining tumour behaviour. Evaluation of melanogenesis-related gene expression and, in particular, the activity of pheomelano-genesis may therefore represent a valuable approach for melanoma classification, prog-nosis, and therapeutic decision-making.

Phenothiazine derivatives have been used for decades as antipsychotic drugs in multiple mental health and physical conditions treatment (schizophrenia, mania in bipolar disorder, and psychosis). Epidemiological studies have shown that people with schizophrenia are less likely to suffer from cancer, which indicates the ability of antipsychotics to inhibit the development of cancer cells. It is our third review about the impact of phenothiazine derivatives on cell death. Here, we focused on apoptosis. We selected 92 papers that investigated the effect of phenothiazine derivatives on the apoptosis process in normal and cancer cell lines. Chlorpromazine, fluphenazine, levomepromazine, mepazine, perphenazine, promazine, promethazine, thioridazine, trifluoperazine, and trifluoperazine analog (3dc) more often induce apoptosis in cancer cell lines, human hepatocytes, and lymphocytes, and the final effect depends on the type and concentration of drug used, the type of cell line, and the methodology used. The obtained results allow for a better understanding of the biological action of phenothiazine derivatives and will help reposition this group of drugs to cancer treatment, resulting in faster, safer, easier, and cheaper therapy.

Medicines used in the treatment of viral infections usually reduce symptoms. There is a need to develop drugs that inhibit the viruses and do not merely relieve the symptoms. Natural bee products possess many pharmacological properties and are widely used in folk medicine. There are many studies on the antibacterial effects of bee products but little is known about their antiviral effects. An extensive literature search was conducted to find and summarize all articles about the antiviral activity of bee products such as bee bread, bee pollen, bee venom, beeswax, honey, propolis, and royal jelly. Analysis of the results showed that these products significantly affect RNA and DNA viruses, which are responsible for respiratory and digestive diseases. The bee products described in the review decrease the half‐maximal inhibitory concentration (IC ₅₀ ) and the half‐maximal effective concentration (EC ₅₀ ); they also increase the selectivity index (SI) values in comparison with controls. The mechanism of the antiviral effect of these products varies widely depending on the type of product and the virus. Thus, more in vitro and in vivo studies should be performed to confirm the use of bee products as a safe and promising adjunctive treatment in antiviral therapy. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Human cutaneous malignant melanoma is a skin cancer that develops from melanocytes, the cells specialised in the production of eu- and pheomelanin. A growing body of evidence suggests that pheomelanin in particular is involved in melanoma development. The aim of this study was to develop a new method enabling the determination of the pheomelanin in formalin-fixed paraffin-embedded (FFPE) tissue specimens of human nodular (NM) and superficial spreading (SSM) melanomas. The pheomelanin level was evaluated in a small amount of material obtained from FFPE melanoma samples (less than 1 mg), using a multi-step procedure of paraffin removal, tissue rehydration, and homogenisation, omitting the melanin isolation step. The obtained product was studied for pheomelanin content using the Py-GC/MS/MS method operating in a multiple reaction monitoring (MRM) mode. The results of our research confirmed the presence of all the pheomelanin markers in the FFPE human melanoma specimens and showed that the tissues analysed contained different amounts of pheomelanin isomers (5-S-cysteinylDOPA and 2-S-cysteinylDOPA). The developed Py-GC/MS/MS procedure enables sensitive quantification of pheomelanin in FFPE human melanoma samples, facilitating broader studies on its role in melanoma development and progression. This method opens new avenues for investigating pheomelanin’s involvement in melanoma malignancy.

Introduction: Nitric oxide (NO) is a potent modulator of programmed cell death, with the ability to both induce and prevent apoptosis. Some of the factors that are capable of triggering apoptosis of skin cells also cause NO overproduction in the epidermis. Unlike keratinocytes,...

Echinacea is a widely used plant medicine, valued especially for its well-documented ability to stimulate the immune system. It has been suggested that melanin could be one of the bioactive factors responsible for the immunostimulatory properties of the plant. The biological functions of melanin pigments are closely related to their chemical composition and structural features. The aim of this study was to characterize the melanin from Echinacea purpurea based on the analysis of thermal degradation products of the well-purified pigment extracted from the dried herb. The melanin was pyrolyzed, and the resulting products were separated by gas chromatography and identified using a triple quadrupole mass spectrometer operating in full scan and multiple reaction monitoring modes. Three groups of marker products were detected in the melanin pyrolysate: polyphenol derivatives, nitrogen-containing heterocycles devoid of sulfur, and benzothiazines/benzothiazoles. This suggests that E. purpurea produces three structurally different melanin pigments: allomelanin, eumelanin, and pheomelanin, which in turn may affect the biological activity of the herb. Our results provide the first-ever evidence that plants are capable of synthesizing pheomelanin, which until now, has only been described for representatives of the animal and fungal kingdoms.

The up-to-date records show that approximately 10% of people worldwide suffer from periodontal diseases and about 50% of adults have some sort of moderate oral cavity disease. Therefore, oral cavity diseases represent the group of the most common chronic inflammatory diseases in the world. Thus, novel, natural, safe, and effective methods of treatment need to be found. In this study, a systematic search was performed in PubMed and Google Scholar up to March 2022 to select research evaluating the activity of propolis against bacteria responsible for oral cavity diseases. Peer-reviewed journals in English containing information about the in vitro and in vivo studies were included in our research. We excluded the records without access, written in another language than English, thesis or book chapters, and review papers, and we rejected the texts when the authors did not write about the antibacterial activity. Collected results of the inhibition zone as well as average MIC and MBC values indicated that propolis exhibits antimicrobial activity against the strains of bacteria which cause, e.g., periodontitis, gingivitis, caries, subgingival plaque, supragingival plaque, recurrent aphthous ulcers (RAS), and pharyngitis. However, before propolis can be commonly used, more research is needed to fully understand its composition and antibacterial mechanism of action.

Oral diseases affect a very large number of people, and the applied pharmacological methods of treatment and/or prevention have serious side effects. Therefore, it is necessary to search for new, safer methods of treatment. Natural bee products, such as honey, royal jelly, and bee venom, can be a promising alternative in the treatment of oral cavity bacterial infections. Thus, we performed an extensive literature search to find and summarize all articles about the antibacterial activity of honey, royal jelly, and bee venom. Our analysis showed that these bee products have strong activity against the bacterial strains causing caries, periodontitis, gingivitis, pharyngitis, recurrent aphthous ulcers, supragingival, and subgingival plaque. An analysis of average MIC values showed that honey and royal jelly have the highest antimicrobial activity against Porphyromonas gingivalis and Fusobacterium nucleatum. In turn, bee venom has an antibacterial effect against Streptococcus mutans. Streptococcus sobrinus and Streptoccus pyogenes were the most resistant species to different types of honey, and royal jelly, respectively. Moreover, these products are safer in comparison to the chemical compounds used in the treatment of oral cavity bacterial infections. Since the antimicrobial activity of bee products depends on their chemical composition, more research is needed to standardize the composition of these compounds before they could be used in the treatment of oral cavity bacterial infections.