Phytochemical analysis, biological activities and molecular docking studies of black and white goji fruits of Lycium ruthenicum Murray

This study analyzes the phenolic and phenylamide composition of black and white goji berries, identifying 31 phenolics, 28 phenylamides, and 3 organic acids. Black berries contained about 10-fold higher phenolics, particularly hydroxybenzoic acid derivatives and anthocyanins, while white berries were dominated by phenolic acids and glycosylated spermidine/spermine derivatives. Glycosides of myricetin and laricitrin in black berries and caffeoyl putrescine monohexosides in both types, were identified. Phenylamide profiles differed, with N-caffeoyl-N′-dihydrocaffeoyl spermidine as the most abundant and bioactive. Both extracts showed antioxidant and enzyme-inhibitory effects. Black goji displayed stronger tyrosinase inhibition consistent with its high phenolic content and synergism among phenolics and phenylamides. Molecular docking revealed strong interactions with AChE and tyrosinase, especially for N-caffeoyl-N′-dihydrocaffeoyl spermidine, which showed higher affinity for tyrosinase than standard inhibitors. The presence of sugar moieties in some compounds reduced binding stability. These results highlight goji berries as promising sources of bioactives, for functional foods and nutraceuticals

Investigation of technological, chemical, biological aspects, and in-silico pharmacokinetic and docking predictions of winter savory (Satureja montana L.) essential oil

Hydrodistillation (HD 205 W and 410 W) and microwave-assisted hydrodistillation (MWHD 90–800 W) were used to prepare essential oil samples from winter savory. Isolated essential oils were analyzed to determine their chemical profiles. Carvacrol was the principal compound, followed by p -cymene and γ-terpinene. Biological activity was assessed using six antioxidant assays, an antimicrobial assay (6 different microbes), and a cytotoxic test (4 cell lines). The MWHD 360 W was the most potent antioxidant agent. The HD 205 W and MWHD 360 W showed the best antimicrobial activity, while the HD essential oil samples were the most potent cytotoxic agents. Molecular docking was performed for the eight most abundant compounds on three proteins: E. coli type I signal peptidase (PDB code 1T7D), P. aeruginosa arginine rhamosyltransferase (PDB code 6J7J), and S. aureus penicillin G acyl-Penicillin binding protein 2a (PDB code 1MWT). Carvacryl acetate and trans- caryophyllene provide the most promising results (the lowest binding energy). The ADMET (absorption, distribution, metabolism, excretion, and toxicity) calculations revealed low toxicity, high skin, blood-brain barrier, and CNS permeability, and high intestinal absorption

Population pharmacokinetic analysis for simultaneous fit of clozapine and norclozapine concentrations in adult psychiatric patients

Background: Clozapine (CLZ) exhibits a high potential for pharmacokinetic interactions due to its extensive and complex metabolism. Additionally, several patient-related factors contribute to the pharmacokinetic variability, making treatment optimization even more challenging. The goal of this study was to develop a parent-metabolite population pharmacokinetic model for CLZ and its primary metabolite norclozapine (NCLZ) and to evaluate sources of variability in a real-world clinical setting. Methods: Data from routine therapeutic drug monitoring (TDM) of 126 adult in- and out-patients with psychiatric disorders were used for the analysis. A nonlinear mixed-effects modeling approach was applied for data analysis to simultaneously fit CLZ and NCLZ concentrations. Results: A one-compartment model for the drug with an additional compartment for NCLZ was used to fit the concentration-time data. The population pharmacokinetic value of oral clearance for CLZ (CL/F) for a typical patient (female, non-smoker) was 26.4 L/h. Male sex and positive smoking status were associated with an increase in CL/F of 25.9 % and 29.2 %, respectively. The estimated value of metabolite clearance (CLm/F) for a typical patient was 29.6 L/h, while male sex and valproic acid (VPA) use were associated with its increases for 45.1 % and 95.5 %, respectively. Conclusion: The developed population pharmacokinetic model describes the simultaneous disposition of CLZ and NCLZ in adult psychiatric patients, accounting for impact of patient and co-therapy factors. In addition to the well-established effects of sex and smoking status on CLZ pharmacokinetics, the model characterizes the significant impact of VPA co-therapy, primarily on NCLZ disposition

Novel N-doped carbon/Co/Co3O4 ternary composites derived by direct carbonization of ZIF-67: Efficient electrocatalysts for oxygen reduction reaction

Cobalt-containing zeolitic imidazole framework ZIF-67 was synthesized in high yield, and directly carbonized by different heating routes at 800 and 900 °C. The products of carbonization, C(ZIF-67)s, were comprehensively characterized in terms of elemental composition (FAAS, EDX, XPS), crystalline (XRD) and molecular structure (FTIR and Raman spectroscopies), morphology (SEM), electrical conductivity, textural (N2 physisorption), and electrochemical properties. It was found that C(ZIF-67)s represent novel meso/microporous ternary composites of the type N-doped carbon/Co/Co3O4, containing metallic Co nanoparticles (NPs) with cubic body-centred crystalline structure, and predominately amorphous Co3O4. They exhibited high electrical conductivity (up to 4.2 S cm−1), notable BET specific surface area (197–265 cm2 g−1), and almost doubled mesopore volume compared to the parent ZIF-67. The effects of carbonization conditions on the structure, physico-chemical properties, and performance of C(ZIF-67)s as electrode materials in electrocatalysis of oxygen reduction reaction (ORR) and charge storage were studied. All C(ZIF-67) composites showed excellent ORR electrocatalytic activity in 0.1 M KOH, with four-electron reduction pathway. The highest ORR activity (the onset potential of −0.13 V vs. SCE) showed the composite produced by gradual heating up to 800 °C followed by holding at that temperature for 3 h. This is attributed to its highest mesopore volume, appropriate meso/micropore structure, high surface content of heteroatom-containing active sites (C–O–C, Co–N, Co–O), high surface Co2+/Co3+ ratio and the presence of Co NPs. The applied direct carbonization of ZIF-67, without additives and post-synthetic modifications, was shown as a simple way to produce meso/microporous electroconducting composites with high potential in energy related applications

Simulation-guided dissolution testing: Coupling DDDPlus™ and GastroPlus® to predict aripiprazole oral bioperformance

Orally administered weakly basic compounds like aripiprazole (ARI) can precipitate in the small intestine due to limited solubility at intestinal pH. This study aimed to identify in vitro biopredictive dissolution tests conditions for ARI immediate release (IR) tablets using a combined GastroPlus® (G+) and DDDPlus™ (D+) modeling approach. ARI solubility was studied in vitro across various pH levels and in biorelevant media, while passive permeability was evaluated using the PAMPA model. These experimental data were used as inputs to build an ARI-specific G+ model, which was used to estimate the in vivo dissolution profiles of ARI following oral administration of IR tablets. D+ was then used to identify in vitro dissolution test conditions predictive of the G+ simulated in vivo dissolution profiles. The in vitro dissolution data for 10 mg, 15 mg and 30 mg ARI IR tablets in 900 mL of compendial media (pH 1.0, pH 4.5 and pH 6.8) using paddle apparatus at 50 rpm and 75 rpm were employed for D+ model development and validation. Experimental findings classified ARI as a low soluble, borderline highly permeable compound. G+ simulations revealed dose-dependent intestinal precipitation followed by subsequent re-dissolution. A three-stage, pH shift dissolution method using basket apparatus was identified as biopredictive of G+ estimated in vivo dissolution profiles, effectively mimicking the G+ simulated precipitation and re-dissolution. This work illustrates an example of how integrated dissolution and absorption modeling can be leveraged to identify biorelevant in vitro test conditions

An insight into pharmacy users’ habits of using herbal products in Serbia: a cross-sectional study

Introduction: Medicinal plants have long been used to treat diseases, and their use in herbal products is increasingly popular, especially for self-medication. This paper aims to assess the prevalence of herbal product use among pharmacy users in Serbia, as well as the motives and awareness regarding their use. Methods: A quantitative, nonexperimental survey research was conducted in community pharmacies across Serbia, involving 2208 respondents. The data were analysed using descriptive statistics (frequencies, percentages) and inferential techniques (Chi-square test and binary logistic regression). Results: Nearly all pharmacy users (97.5%) use various herbal products. They most often use them as needed (39.7%), while 22.8% use them frequently, and a similar proportion use them infrequently (17.9%) or daily (17.1%). The most common motive for their use is to improve health (76.0%). Over half of the respondents (58.4%) reported purchasing herbal products from pharmacies. Additionally, 73.1% of respondents consistently received advice on the use of herbal products from pharmacists. The primary sources of information about herbal products were pharmacists (44.6%) and then the media (22.8%). Most respondents (58.6%) believe herbal products are safe but have some side effects, whereas 30.0% believe herbal products are completely free of side effects. Almost half of the respondents believe herbal products are as effective or more effective than synthetic medicines. Conclusion: Strengthening pharmacists’ role in counselling, developing pharmacy-based strategies, enforcing regulations, promoting pharmacy-based access, and providing pharmacist-led education, together with collaboration among healthcare professionals, regulators, and the media, is essential to ensure safe and informed use of herbal products

Exploiting the Versatile Reactivity of Aryldiazonium Tetrafluoroborate Salts in the Synthesis of New Isochromene-Fused CF3-Substituted Pyrazoles with Anticancer Potential

Pyrazoles, and in particular their fluorinated derivatives, are valuable heterocyclic moieties in medicinal chemistry. Our research group recently developed a one-pot, two-step synthesis of pyrazolo[3,4-c]isochromenes, combining two privileged structures into a single hybrid molecule. Based on the preliminary anticancer screening results of these derivatives, herein, we designed a next-generation compound library focused on the derivatization of a specific portion of the 1-(trifluoromethyl)-3,5-dihydroisochromeno[3,4-c]pyrazole scaffold via late-stage functionalization. The diverse reactivity of aryldiazonium tetrafluoroborate salts was leveraged to achieve this and generate a small but varied compound library. The new series was tested for their anticancer properties and selected derivatives demonstrated pro-apoptotic activity in the human cervical carcinoma cell lines HeLa. The obtained results highlight these structures as valid candidates for further biological studies, while the streamlined synthetic route offers a facile approach to further structural analogs

Concentration of heavy metals in the leaves of rosemary (Salvia rosmarinus Spenn., Lamiaceae) cultivated in urban habitats of Belgrade

Rosemary (Salvia rosmarinus Spenn., Lamiaceae) is widely cultivated as an ornamental plant in urban areas. Due to essential oil, carnosic and rosmarinic acid, its leaves have antioxidant, anti-inflammatory and antimicrobial properties. Rosemary leaves are traditionally used as a bath additive for mild muscle and joint pain and peripheral circulatory disorders, as well as in herbal teas for dyspepsia and mild gastrointestinal spasms. Rosemary is also a common culinary spice. Given the potential health adverse effects of heavy metals accumulated from environmental pollution and pesticide residues, this study analyzed Hg, Pb and Cd concentrations in rosemary leaf samples from seven locations in central and peripheral Belgrade and in two commercial samples. The dried leaves were subjected to microwave mineralization with nitric acid, and metal concentrations were measured by ICPOES. All samples contained heavy metals below the limits for herbal products according to national and European regulations. The highest levels of Hg and Pb were found in a commercial sample from Morocco, while Cd was most abundant in samples from Zemun. The lowest metal levels were found in a sample from the Faculty of Pharmacy’s garden in the outskirts of Belgrade. Acknowledgements: This research was funded by the Ministry of Science, Technological Development and Innovation, Republic of Serbia through two Grant Agreements with University of Belgrade-Faculty of Pharmacy No. 451-03-136/2025-03/200161 and 451-03137/2025-03/200161

Investigating the influence of croscarmellose sodium content on the properties of liquisolid systems prepared with different mesoporous carriers

INTRODUCTION The disintegration of tablets in the gastrointestinal fluids is one of the prerequisites for drug absorption and ultimate therapeutic effect (Bhalani, 2022), which is why most tablet formulations require the use of a suitable disintegrant. Liquisolid systems (LSS) are considered a promising technique for improving the oral bioavailability of poorly soluble drugs. The excipients used for their formulation, such as carriers and coating materials, are usually characterised by a large specific surface area required for their intended use. However, they are often hydrophobic, which leads to slow disintegration of the LS tablets. To ensure adequate wetting and disintegration properties, the choice of the appropriate disintegrant and its concentration in these formulations must be carefully considered (Gavali, 2011). The aim of this study was to investigate how different concentrations of croscarmellose sodium (CCS), a widely used superdisintegrant, affect the mechanical properties of LSS prepared with four different mesoporous carriers, their disintegration time and wetting ability

Diverging Safety Signals: A Trend Analysis of Suspected Adverse Drug Reactions Reporting for Spinal Muscular Atrophy Therapies in the European Union

Background/Objectives: The approval of disease-modifying therapies has significantly improved outcomes for patients with spinal muscular atrophy (SMA), yet their long-term safety profiles remain under continuous evaluation. This study aimed to assess trends in the reporting of suspected adverse drug reactions (ADRs) associated with nusinersen, onasemnogene abeparvovec, and risdiplam across the European Union. Methods: We conducted a secondary analysis of annual suspected ADR data reported to EudraVig- ilance from 2017 to 2024 for the three approved disease-modifying therapies for SMA. On top of general reporting trend, specific adverse reactions of interest included post- lumbar puncture syndrome for nusinersen, liver toxicity and elevated serum troponin for onasemnogene abeparvovec, and respiratory and gastrointestinal reactions for risdiplam. Joinpoint regression analysis was used to evaluate annual percent changes and identify statistically significant trend segments for each medicine. Results: The reporting of sus- pected ADRs for nusinersen showed an initial increase, followed by a significant decline after 2019. Onasemnogene abeparvovec exhibited a continued but decelerating increase in suspected ADRs, while risdiplam demonstrated a consistent upward trend across all reported reactions. Conclusions: Diverging patterns in adverse reaction reporting sug- gest a stabilizing safety profile for nusinersen and potential emerging safety signals for risdiplam and onasemnogene abeparvovec, underscoring the need for ongoing continued pharmacovigilance (e.g., post-authorization studies and spontaneous reporting)