Asthma, a chronic inflammatory disorder of the airways, presents a significant global health burden. The search for effective therapeutic interventions, especially from natural sources, remains imperative. Our study investigates the therapeutic potential of Manilkara zapota L. P. Royen (Sapodilla) in alleviating chronic asthma in rats. It elucidates its mechanism of action, focusing on the interleukin-1 beta (IL-1ß) pathway while identifying ß-sitosterol as a crucial bioactive compound.

Using a rat model of chronic asthma induced by ovalbumin sensitization and challenge, we demonstrate that M. zapota administration effectively attenuates airway inflammation and hyperresponsiveness. Histopathological analysis reveals reduced inflammatory cell infiltration and mucus hypersecretion in the lung tissues of treated rats. Mechanistically, our findings indicate that M. zapota treatment significantly decreased IL-1ß, a key mediator of airway inflammation. Additionally, our investigation identifies ß-sitosterol, a phytosterol abundant in M. zapota, as a major bioactive constituent responsible for its therapeutic effects in asthma.

This study sheds light on the therapeutic potential of M. zapota in managing chronic asthma by targeting the IL-1ß pathway, offering insights into the underlying mechanisms of action. Furthermore, identifying ß-sitosterol as a key component underscores the importance of natural products in drug discovery and development for respiratory disorders. These findings warrant further exploration and potential clinical translation of M. zapota based therapies for asthma management.

Rubus fruticosus L. phytochemicals represent a rich source of bioactive molecules with antioxidant, anti-inflammatory, and neuroprotective potential. These polyphenolic compounds enhance endogenous antioxidant enzymes such as superoxide dismutase and catalase, mitigating oxidative stress and potentially delaying cognitive decline. Their ability to stimulate α-secretase and inhibit β-secretase suggests interference with amyloid aggregation, a central process in Alzheimer’s disease (AD) pathology.

Comprehensive in silico pharmacokinetic profiling (SwissADME, pkCSM, DEEP-pk) indicated high gastrointestinal absorption for all analyzed phytochemicals (p-coumaric acid: 91.12%, daidzein: 93.04%, 4-hydroxybenzoic acid: 77.49%, cinnamic acid: 94.02%, ferulic acid: 94.10%, guaiacol: 93.37%) and favorable blood–brain barrier permeability. Compounds exhibited logBB values from -0.315 to 0.205 and logPS values from -2.5 to -1.924, surpassing the respective thresholds (-1 and -3) and demonstrating superior predicted brain accessibility compared with galantamine (logPS = -3.022).

Compounds from R. fruticosus L. fractions displayed consensus LogP values < 5 (1.05-2.24), TPSA ≤ 140 Ų (29.46-70.67 Ų), and bioavailability scores of 0.85, except for daidzein and guaiacol (0.55). Unlike galantamine, these molecules are not predicted to be P-glycoprotein substrates, suggesting reduced efflux and improved CNS bioavailability. Compared with galantamine, the phytochemicals exhibited equal or higher predicted oral bioavailability (0.85) and full compliance with Lipinski, Veber, and Egan filters, with at most a single Muegge or Ghose rule violation. Predicted skin permeability values further support their systemic absorption potential.

To validate these predictions, 5xFAD mice (n = 40) were randomly assigned to three treatment groups (FT, FH, LH; n = 10 per extract, with 5 mice receiving 50 mg/kg and 5 receiving 100 mg/kg), a negative control group (NaCl, n = 5), and a positive control group treated with a standard AD medication, galantamine (n = 5). All treatments were administered via oral gavage for seven consecutive days and one hour prior to behavioral testing. Behavioral outcomes were assessed using standardized tests, and statistical analyses were performed to determine significance between groups (p < 0.05). Cognition, as well as anxiety- and depression-like behaviors, were evaluated using the Y-Maze, Open Field Test, Novel Object Recognition Test, Elevated Plus Maze, and Forced Swim Test. Behavioral assays revealed significant improvements in spatial and recognition memory, as well as anxiety- and depression-like behaviors. Distinct dose-dependent patterns were observed among the R. fruticosus L. fractions. FT exhibited an inverse dose–response, with the 50 mg/kg dose yielding superior cognitive performance, enhanced working and recognition memory, and reduced anxiety- and depression-like behaviors. In contrast, FH showed a classical dose–response, with higher doses (100 mg/kg) improving cognition, while lower doses increased general locomotor activity without enhancing cognition, likely reflecting general arousal rather than targeted exploration. These findings corroborate the computational predictions of BBB permeability and multitarget engagement, highlighting the translational relevance of this integrated approach.

This combined computational-experimental strategy highlights R. fruticosus L. phytochemicals as promising multitarget candidates for AD therapy and underscores the value of in silico modeling in prioritizing molecules with optimal CNS accessibility for preclinical investigation.

Introduction. Marigolds are characterized by a rich composition of biologically active substances, a complex effect on the body and low side effects. They are widely cultivated in Ukraine. However, activity of plants extracts depending on many factors, including the part of the plant, geographical source, extraction method, etc. So, we prepared extracts from marigold Tagetes patula L. flowers in 64% and 70% ethanol. The effects of the extracts on the morphological and functional properties of cells, antioxidant potential and antiviral activity were studied.

Methods. The influence of the extracts on viability of tumor cells (A549 – lung cancer and Нер-2 – laryngo carcinoma) were studied using fluorescence microscopy, MTT and trypan blue assays. The in vitro antioxidant activity of the extracts was measured by the free radical scavenging capacity according to the DPPH test. Antiviral activity was determined using yield reduction assay.

Results. Morphological changes of human tumor cell were detected, namely their rounding, granularity, increase in size, and swelling. The mitochondrial activity of the cells at the used concentrations of extracts was within 45 - 100%. However, a study of cell membrane permeability revealed inhibition of A549 and Hep-2 cells viability under the influence of extracts by 18-79% and 19-66%, respectively. In addition, analysis of the mitotic activity of tumor cells under the action of the extracts showed a significant decrease in their mitotic index. High antiradical activity and the ability of both extracts to absorb DPPH radical were shown. Also, a similar pronounced antiherpetic efficiency of both extracts was established, the decreasing of herpes simplex virus type 1 infectious titer was in the range of 1.7 - 4.7 log₁₀ TCID₅₀/ml.

Conclusions. These findings suggest, that extracts obtained from marigold Tagetes patula L. flowers may hold promise as a potential therapeutic agents.

Erectile dysfunction (ED) is a prevalent male sexual disorder frequently associated with impaired nitric oxide signaling, heightened oxidative stress, and the dysregulation of key enzymes such as acetylcholinesterase, arginase, phosphodiesterase-5 (PDE-5), and angiotensin-I converting enzyme (ACE). Limitations of current pharmacotherapies, including side effects and incomplete efficacy, have spurred interest in plant-derived bioactive compounds as alternative or complementary treatments. Although Sida linifolia is traditionally used for managing reproductive and inflammatory conditions, its mechanism of action remains unclear. This study explored the propensity of the ethanolic fraction of S. linifolia leaves (EtOHFSL) to inhibit enzymes linked to erectile dysfunction in rat penile tissue homogenate. Enzyme inhibition assays were conducted using rat penile tissue homogenates, while phytochemical constituents were identified using gas chromatography coupled with flame ionization detection (GC-FID) and supported by high-performance liquid chromatography (HPLC) profiling to confirm compound composition. Molecular docking studies (MDS) were performed using AutoDock Vina. Identified compounds in EtOHFSL included epicatechin, flavone, rutin, kaempferol, lunamarin, naringenin, ellagic acid, quercetin, and chlorogenic acid. EtOHFSL demonstrated moderate, concentration-dependent inhibition of PDE5, arginase, ACE, and AChE, with IC₅₀ values ranging from 0.66–0.84 mg/mL, which were compared cautiously with the respective pure reference inhibitors (sildenafil, L-NOHA, captopril, and galantamine) for reference purposes only. Molecular docking of experimentally confirmed phytochemicals such as epicatechin, rutin, kaempferol, lunamarin, and ellagic acid revealed strong binding affinities to ED-related enzymes. The in-vitro results corroborated in-silico molecular docking predictions, suggesting consistent inhibitory trends. In-silico ADMET predictions further indicated acceptable pharmacokinetic and toxicity profiles for most compounds. These preliminary findings suggest that S. linifolia contains bioactive constituents with enzyme modulatory potential against ED-related targets; however, further purification, isolation of active principles, and in-vivo validation are required to substantiate any therapeutic claims.

This study investigated the mycochemical composition and bioactive potential of three wild mushroom species—Cortinarius trivialis, Mycena pura, and M. rosea—sampled from Tara Mountain, Serbia. The focus was on their polyamine content, total phenolics, total flavonoids, antioxidant capacity (DPPH, ABTS, NO, and FRAP assays), and acetylcholinesterase (AChE) inhibitory activity. Polyamines (PAs) (putrescine, spermidine, spermine) were quantified in lyophilized fungal samples using high-performance liquid chromatography with fluorescence detection (HPLC-FD). In addition, total phenolics, total flavonoids, antioxidant capacity, and anti-AChE activity were determined from 80% methanolic extracts using previously established spectrophotometric methods. Quantification of putrescine (PUT), spermidine (SPD), and spermine (SPM) revealed C. trivialis as particularly enriched in PUT (47.51 ± 15.92 mg/kg d.w.) and SPD (41.58 ± 18.06 mg/kg d.w.), while M. pura and M. rosea contained lower amounts. M. pura stood out for its high phenolic and flavonoid content, driving strong antioxidant activity across DPPH, ABTS, FRAP, and NO radical assays. M. rosea displayed selective ABTS scavenging and the strongest AChE inhibition (93.24 ± 7.90%), whereas C. trivialis, despite modest antioxidant activity, combined rich polyamine levels with notable AChE inhibition. Principal component analysis underscored distinct metabolic signatures: phenolic-driven antioxidant defense in M. pura, SPD-associated neuroprotection in M. rosea, and high PUT accumulation in C. trivialis.

To the best of our knowledge, this is the first report linking polyamine profiling with AChE inhibition in these mushroom species. The findings highlight a species-specific interplay of polyphenols and polyamines in shaping antioxidant and neuroprotective activities, positioning these inedible fungi as promising reservoirs for bioactive compounds with potential applications in functional foods, nutraceuticals, and neuroprotective strategies.

The rise of antimicrobial resistance (AMR) to the plethora of current antibiotics constitutes a major threat to public health, urging for the discovery of novel antibiotics through natural products. This study explores the potential of ten cinnamaldehyde analogues as novel antibacterial agents against model organisms, namely Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Antibacterial activity and structure-activity relationships (SARs) were assessed using high-throughput screening (HTS) and minimum inhibitory concentration (MIC) assays, with ampicillin included as a standard control compound. Synergy was evaluated through checkerboard assays with ampicillin and neomycin. Hydroxylated cinnamaldehyde analogues, namely 1.2 and 1.3, exhibited enhanced bioactivity against Escherichia coli when compared to the parent compound (cinnamaldehyde). Most ketone derivatives resulted in minimal or reduced potency with the exception of 2.3 (MIC at 5mM with a 17.26% growth). Compounds 1.1, 1.2, 1.3 aldehydes exhibited an MIC (5 mM, 2.5 mM, 0.016 mM respectively) and adequate microbial growth inhibition (2.33-9.49%) for Staphylococcus aureus. Interestingly, ketones 2.3, 2.4 resulted in MICs at 5 mM with ~ 15% microbial growth. As for Pseudomonas aeruginosa, a similar trend of ketone inactivity was observed with none of them achieving more than 55.8% inhibition. The aldehyde group here presented better efficacy. Specifically, compounds 1.1, 1.2 with MIC = 5 mM and MIC = 2.5 mM respectively. Notably, compound 1.1 was able to achieve complete inhibition at the concentration of 5 mM. The importance of keeping the aldehyde core while strategically adding hydroxyl groups and bromine for antimicrobial efficacy was highlighted through SAR analysis. Synergistic effect trials with ampicillin and neomycin revealed mainly indifferent interactions, with cases of additive and synergistic effects related to potency alone.

Due to their increasing prevalence, obesity and infectious diseases represent major public health problems, which is why effective therapeutic alternatives need to be found. There is considerable interest in the potential health benefits of cherry stems, a by-product of the agri-food industry. In this work, we studied the impact of the ethanolic extract of cherry stems on the inflammation and oxidative stress associated with obesity, as well as its antibacterial effect. In addition, acute oral toxicity was assessed in female BALB/c mice. Furthermore, the quantity of bioactive substances was estimated in the cherry stems extract. To do this, a phytochemical analysis was carried out, then the biological activities related to obesity reduction were examined in vitro and in vivo. The effect of the extract on several pathogens was also assessed, as well as its synergy with antibiotics. The in vitro studies have shown significant amounts of vitamin C and phenolic compounds (3.93 mg ASE/g and 215.52 ± 2.46 mg GAE/g extract, respectively). At a concentration of 01 mg/ml, the extract showed a significant anti-inflammatory (67.11%), antioxidant (60.17 and 64.23%) and anti-obesity (28.29 and 76.66%) properties. The acute oral toxicity of crude ethanolic cherry stem extract, even at high doses, revealed no observable toxicity. The data indicate that cherry extracts exhibit significant antimicrobial activity, with growth inhibition levels ranging from 10 to 98.50%. This is mainly attributed to their bioactive composition. When this extract is combined with antibiotics, they enhance the inhibition of bacterial proliferation, showing an encouraging synergistic effect. In addition, this plant has demonstrated bactericidal action (66.66 - 77.77%) against various strains of pathogenic bacteria. All these factors suggest that cherry stems could be a natural alternative for combating bacterial infections and obesity and their related disorders.

Introduction: Several diseases are associated with oxidative stress caused by free radicals. Current research focuses on finding naturally occurring antioxidants and antidiabetic agents of plant origin in treating oxidative-stress-related diseases. This study investigated the antioxidant and antidiabetic activities of methanolic and n-hexane essential oil extracts of Momordica charantia (bitter melon). Methods: The oils from the seeds of M. charantia were extracted with methanol and n-hexane, respectively, and their chemical constituents were analysed and quantified by GC-MS analyzer. The antioxidant activities of both oil extracts were measured by 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), Hydroxyl radical (OH^.), and nitric oxide (NO) scavenging assays, while the antidiabetic activities were determined in vitro using the α-amylase and β-glucosidase assays.

Results: The GC-MS analysis revealed that methanol and n-hexane extracts of Momordica charantia seed oil are abundant in fatty acids such as pentadecanoic acid, octadecanoic acid, and cyclocoeicosanetriluoroacetic acid, and they both significantly demonstrated profound antioxidant and antidiabetic activity comparable to the reference antioxidant compound (ascorbic acid) and reference antidiabetic compound (acarbose). The essential oil from the methanol extract caused better inhibition of DPPH (89.69%), OH^. (75.12%), and NO (74.19%) at the highest concentration (500 μg/mL) investigated, despite both oils showing a dose-dependent antioxidant activity. The oils of the two solvents of M. charantia seeds also expressed dose-dependent inhibitory activity for α-amylase and β-glucosidase comparable to acarbose; however, the n-hexane oil extract demonstrated better antidiabetic activity for β-glucosidase (IC50 = 29.89 ± 0.051 μg/mL) compared to the methanolic oil extract (IC50 = 58.59 ± 0.047 μg/mL).

Conclusion: The results conclude that M. charantia seed oils are a good source of polyunsaturated fatty acids and afford an essential basis for the use of the oil in the treatment of oxidative-stress-related diseases like diabetes mellitus.

Introduction: Atherosclerosis remains the leading cause of mortality from cardiovascular diseases. It is driven by lipid accumulation within arterial walls due to retention of low-density lipoproteins (LDL). Among the atherogenic LDL modifications, desialylation — the enzymatic removal of terminal sialic acids from surface glycans — represents a critical but insufficiently studied mechanism. This study aimed to establish a novel in vivo model of sustained LDL desialylation in apolipoprotein E-knockout (ApoE-KO) mice and assess its contribution to atherosclerosis progression.
Methods: Vibrio cholerae neuraminidase (Neu) was conjugated to murine IgG using EDAC, purified by affinity batch chromatography, sterilized by filtration and validated by PAGE. Male ApoE-KO maintained on a chow diet received repeated Neu injections for 6 weeks. LDL desialylation was quantified by the thiobarbituric acid assay. LDL atherogenicity was assessed using RAW264.7 macrophages. Morphometric analysis of aortic lesions was performed. Biochemical and hematological parameters were measured to evaluate systemic toxicity.
Results: Neu administration significantly reduced LDL sialic acid content and enhanced cholesterol accumulation in RAW264.7 macrophages incubated with LDL from treated ApoE-KO mice, compared with LDL from wild-type mice. Treated animals exhibited elevated LDL/HDL ratio and LDL cholesterol levels, and a significant enlargement of atherosclerotic lesions. Importantly, Neu treatment did not induce adverse changes in biochemical or hematological parameters, indicating the absence of systemic toxicity.
Conclusions: We developed a novel in vivo model that replicates the enhanced atherogenicity of desialylated LDL and its contribution to atherosclerotic lesion progression. This study provides an experimental platform for studying glycosylation-dependent mechanisms in atherosclerosis and highlight LDL desialylation as a potential therapeutic target.

An original thermodynamic framework has been developed to describe precipitation–dissolution phenomena of drugs in aqueous systems containing cyclodextrins and auxiliary agents. The central innovation is the degree of drug precipitation, derived from new mass balance equations combined with the Law of Mass Action. This parameter quantifies the fraction of drug present in the solid phase and directly indicates solubility limitations under defined conditions. The methodology allows determination of species distributions—including free drug, ionized forms, binary complexes, and ternary complexes—across aqueous and solid phases as functions of pH and composition. Species molar fractions are normalized to the total apparent solubility, ensuring internal consistency. To support visualization, Diagrams of Heterogeneous Chemical Equilibria were introduced, involving three steps: (i) thermodynamic evaluation of solid-phase stability using precipitation degree, (ii) calculation of molar fractions within stability regions, and (iii) assessment of homogeneous systems containing only soluble species by conventional equilibrium methods. Application to ten commercial drugs, including cimetidine, flurbiprofen, indomethacin, and naproxen, confirmed the predictive capacity of the model. By integrating available equilibrium constants, the methodology quantitatively predicts the extent of drug precipitation and reveals synergistic effects in drug–cyclodextrin–auxiliary agent systems. These predictive advantages are particularly relevant for poorly soluble pharmaceuticals, as the framework identifies conditions where solubility is maximized and precipitation minimized. Overall, the proposed methodology provides both quantitative and graphical tools for analyzing phase behavior, solubility dynamics, and cooperative effects in drug formulations. Beyond pharmaceuticals, the framework has potential applications in environmental and materials science where heterogeneous equilibrium processes of poorly soluble compounds are critical.