Chios mastic gum (CMG), the resin of Pistacia lentiscus var. Chia, is a product with great ethnopharmacological and economic significance. This study attempts to investigate, for the first time, the activity of CMG, its fractions and isolated compounds against specific enzymes, which play pivotal roles in the degradation of proteins contained in skin connective tissue. Initially, crude CMG was subjected to extraction, fractionation and isolation through different chromatographic techniques to obtain the acidic and neutral fraction of terpenes. Additionally, the characteristic and major active triterpene acids of CMG, masticadienonic and isomasticadienonic acids (MNA, IMNA) were isolated in pure form. All samples were analysed by means of High-Performance Thin-Layer Chromatography (HPTLC) with four distinct development systems to obtain their constituents’ profile. Finally, samples were tested for their ability to inhibit the elastase and collagenase enzymes. According to our findings, for collagenase, a mixture of MNA and IMNA demonstrated the most potent activity with an IC₅₀ value of 31.07 μg/mL, while for elastase CMG’s acidic fraction provided the most promising results with an IC₅₀ value of 17.30 μg/mL. Overall, these results attempt to fill the gap in scientific knowledge about the use of CMG and its constituents in skincare and cosmetic products.

The Set and Ring domain of the UHRF1 oncogene is responsible for its interaction with hemimethylated DNA and faithful propagation of epigenetic signaling over cellular replication. Inhibiting this recognition can have serious implications for UHRF1 functionality and may possibly enable therapeutic interventions. Based on a previous finding indicating a promising in vitro DNA demethylating potential of a pyrimidine derivative, a subscaffold search was performed in the NCI/DTP compound repository to discover similar molecules and evaluate their affinity for the SRA domain of UHRF1. Toward this direction, several compounds were evaluated using a thermal melt screen, and the most promising hits were subsequently studied by calorimetry in terms of their capacity to bind the 5-methylcytosine recognition site of UHRF1. A markedly different thermodynamic profile between the two confirmed hits with an intense enthalpy-entropy compensation signature was determined. The systems were further studied by biased and unbiased molecular simulations, computational hydration mapping, and calorimetry-based heat capacity measurements to devise a hypothesis on the structural requisites for efficient SRA binding. The most potent compound was evaluated for its DNA methylation effects against the UHRF1-dependent colorectal cancer HCT116 cells, where promising global demethylating activity reaching an approximate 75% reduction compared to control was achieved after treatment with 25 μM of NSC232005. Based on the presented results, rationally substituted analogues of the uracil scaffold appear as highly promising UHRF1 modulators for exploring its diverse functionalities and validating the protein as a drug target.

Background/Objectives: Ecballium elaterium is a widely distributed species and is one of the earliest recorded in traditional medicine. With global temperatures rising, this study aimed to investigate the changes in E. elaterium plantlets subjected to thermal stress. The goal was to understand how thermal stress affects morphology, physiology, and bioactive metabolite production, both for ecological adaptation and potential therapeutic applications. Methods: Seedlings were cultivated under controlled conditions and subjected to either the control temperature (22 °C) or the heat stress temperature (35 °C) for one week. Morphological and anatomical traits were assessed, along with physiological parameters such as chlorophyll content, malondialdehyde (MDA), hydrogen peroxide (H₂O₂), L-proline, soluble sugars, and total phenolic content. Methanolic leaf extracts from both groups were analyzed via LC-HRMS/MS and examined in vitro for cytotoxic activity against three human cancer cell lines: MCF-7 (breast), DU-145 (prostate), and SH-SY5Y (neuroblastoma). Results: Heat stress reduced dry mass and stomatal density but increased the diameter of the root transition zone, indicating anatomical adaptation. Leaves exhibited elevated oxidative stress markers and altered metabolite accumulation, while the roots showed a more integrated stress response. LC-HRMS/MS profiling revealed significant shifts in Cucurbitacin composition. Extracts from heat-stressed plants displayed stronger cytotoxicity, particularly toward DU-145 and SH-SY5Y cells, correlating with higher levels of glycosylated Cucurbitacins. Conclusions: E. elaterium demonstrates organ-specific thermotolerance mechanisms, with heat stress enhancing the production of bioactive metabolites. These stress-induced phytochemicals, especially Cucurbitacins, hold promise for future cancer research and therapeutic applications.

Background: The germination and early development of Origanum vulgare L. subsp. hirtum (Link) Ietswaart (Greek oregano) were studied to assess the plant’s response to different temperatures. Methods: After germination, seedlings were cultivated in control (25 °C) and cold (15 °C) chambers with standard growth parameters. Comparative analyses of plant morphology and leaf anatomy were conducted to identify structural modifications induced by different temperatures. Physiological evaluations, including photosynthetic pigment measurements, phenolic content, and antioxidant activity, were performed to assess differences between the plants grown under the two temperature conditions. Methanolic extracts from the leaves were tested for cytotoxicity on MCF-7 breast adenocarcinoma cells and SH-SY5Y neuroblastoma cells, as well as on nine microbial strains. Additionally, biomarkers from the leaves affected by temperature changes were determined using LC-HRMS/MS analysis. Results: Comparative analyses revealed distinct structural and physiological modifications under cold conditions. The methanolic extracts from plants grown at 15 °C exhibited notably higher cytotoxic activity in both cell lines but demonstrated no activity against microbial strains. The results highlight the influence of low temperature on enhancing the bioactive properties of Greek oregano. Conclusions: The findings provide valuable insights into the environmental adaptability of oregano, demonstrating the impact of low temperature on its bioactive properties. The therapeutic potential of methanolic extracts cultured at 15 °C is imprinted in cytotoxicity in SH-SY5Y and MCF-7 cells and the absence of any activity against microbial strains.

A recent ethnobotanical study collected traditional knowledge on treatments and plants of tribes in Uíge, Northern Angola, a region suffering from infant malnutrition and mortality. Aqueous extracts of twelve different plant species (leaves or stems) collected were prepared and subject of chemical profiling. The impact of twelve plant extracts on mammary epithelial cell differentiation was tested in vitro by dose-dependent treatment of HC11 cells. Leaf extracts of Carica papaya and Morinda lucida induced HC11 differentiation and elevated the mRNA expression of the milk protein β-casein, while the remaining ten inhibited the HC11 mammary differentiation.The majority of the plant extracts did not induce in vitro mammary epithelial cell differentiation assuming that the plants might rather exert their effects on prolactin levels or on other mechanism influencing the mammary gland health. Phenolic acids and flavonoids were identified as the predominant and potentially active chemical classes responsible for the observed lactogenic effects.

Insecticide resistance in mosquitoes, largely mediated by cytochrome P450 monooxygenases (CYPs), compromises the efficacy of vector control tools. In this study, chemically-wise selected natural extracts and compounds were screened for their CYP inhibition potential. Among 37 tested plant extracts and fractions, a decarboxylated acidic fraction of industrial hemp ( Cannabis sativa Linnaeus var. ‘Futura 75’) emerged as a promising hit, and phytochemical profiling identified cannabidiol (CBD) as its major component (IC₅₀ = 18.37 μM for CYP9K1). CBD was used as a scaffold to generate semisynthetic analogues; of which a piperazinyl analogue outperformed the natural scaffold demonstrating significantly greater potency (IC₅₀ = 2.50 μM for CYP9K1). Docking studies using homology-derived CYP9K1 models also supported a stronger binding affinity of the piperazinyl analogue relative to CBD. Toxicity assays using pyrethroid-resistant Anopheles gambiae Giles adults confirmed that neither CBD nor the piperazinyl analogue had intrinsic toxicity, yet the semisynthetic analogue significantly enhanced deltamethrin efficacy, showing a threefold synergistic effect. The safety profile of the cannabis compounds for non-target organisms was evaluated through human cell line cytotoxicity tests and bee toxicity assays, suggesting low non-target organism toxicity. Our study describes the identification of a plant-derived synergist lead with strong potential as an insecticide additive to combat metabolic resistance in malaria-transmitting mosquitoes.