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Background/Objectives: This study aimed to develop gastroretentive tablets based on mucoadhesive-floating systems with encapsulated gentian ( Gentiana lutea , Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Methods: Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). Results: The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Conclusions: Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation.

The current trend in food innovations includes developing products containing plant ingredients or extracts rich in bioactive compounds. This study aimed to prepare and characterize skimmed thermally treated goat's milk powders enriched with lyophilized fruit extracts of Lycium ruthenicum Murray (GMLR) and Lycium barbarum L. (GMLB). Proximate analysis, ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), Fourier transform infrared spectroscopy using attenuated total reflection (FTIR-ATR), and electrophoretic analysis were assessed. Total phenolic content (TPC), total protein content, and antioxidant properties of enriched goat milk powders were determined spectrophotometrically, and prebiotic potential was evaluated by the broth microdilution method. A total of 25 phenolic compounds and 18 phenylamides were detected in the enriched goat milk powders. Electrophoretic analysis showed the absence of proteolysis in the prepared powders. The GMLR showed the highest TPC and displayed a ferric ion-reducing power, probably contributed by anthocyanins and some phenylamides. GMLR and GMLB had higher ABTS radical scavenging activity but lower ferrous ion-chelating capacity than control goat's milk powder. GMLB and GMLR in a dose-dependent manner (0.3-5 mg/mL) showed a growth-promoting effect on probiotic strains. In summary, prepared goji/goat milk powders, primarily GMLR, might be used as prebiotic supplements or functional food additives.

The aim of this study was to identify and characterise different classes of bioactive compounds from freeze-dried red goji berries (RGB) grown in Serbia, using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC Q-ToF MS). In addition, this study aims to demonstrate the importance of applying the advanced UHPLC Q-ToF MS technique in the identification of various biocompounds. The analysis showed the presence of 28 phenolic compounds, 3 organic acids, and 26 phenylamides. The 2-O-β- d -glucopyranosyl- l -ascorbic acid (AA-2βG) was identified by UHPLC Q-ToF MS and quantified by standardised UHPLC-DAD method. Most of the compounds detected were derivatives of caffeic acid and ferulic acid, followed by quercetin derivatives. Among the phenylamides, several glucosylated caffeoyl and/or dihydrocaffeoyl derivatives of spermidine and spermine were characterized, confirming their recent characterization. Some glycosylated/non-glycosylated putrescine derivatives and caffeoyl-dihydrocaffeoyl-feruloyl spermidines were identified in goji berriesfor the first time. Their tentative structures and fragmentations were proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cultivation of goji berries (GB), fruits of Lycium barbarum L. (Solanaceae), is expanding worldwide, including in Europe. In this study, a comparative analysis of the nutritional value, chemical composition and in vitro biological activities of GB from different locations in Serbia was performed. Proximate compositions were evaluated according to standard methods. Minerals were assessed by inductively coupled plasma techniques, while fatty acids, sterols, and phenolic profiles were analyzed by gas- and liquid chromatography-based techniques coupled with flame-ionization, mass spectrometry, or diode array detection. The total content of phenolics, flavonoids, carotenoids, and polysaccharides was assessed using spectrophotometric methods. Methanol extracts from GB were examined for their antioxidant, enzyme inhibitory (α-amylase, α-glucosidase, acetylcholinesterase and tyrosinase) and antibacterial activities. Despite significant variations among samples from different locations, the results confirmed that GB are a valuable source of dietary fiber and protein and are characterized by favorable fatty acid profiles. Phytochemical analysis revealed that β-sitosterol, Δ 5 -avenasterol, and 24-methyldesmosterol are the predominant sterols and caffeic acid, gallic acid, quercetin and rutin are the main phenols. All GB samples showed both antioxidant and mild antimicrobial activity. A dose-dependent anti-enzymatic activity (IC 50 ranging 1.68-6.88 mg/mL) was demonstrated. The results support further promotion of GB cultivation in Serbia and further investigations on their potential applications in various industries., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Herein we describe the antioxidant, antimicrobial, antibiofilm, anti-inflammatory and wound-healing potential of aqueous and polysaccharide extracts from three widely appreciated mushrooms: Agrocybe aegerita , Laetiporus sulphureus and Agaricus bisporus . Moreover, we present their detailed phenolic, polysaccharide and protein profiles and ATR-FTIR spectra. The study found that polysaccharide extracts (PEs) from mushrooms had higher total and β -glucan levels than aqueous extracts (AEs), with A. aegerita showing the highest content. L. sulphureus had a higher total protein content, and A. aegerita AE had the highest phenolic content. Our results indicate that all the tested extracts have high potential regarding their bioactive properties, with A. aegerita being the most promising one. Namely, the antibacterial activity assay showed that the development of the skin-infection-causing agent, Staphylococcus aureus , was inhibited with a minimal inhibitory concentration of 4.00 mg/mL and minimal bactericidal concentration of 8.00 mg/mL, while the results regarding wound healing showed that, over the course of 24 h, the A. aegerita extract actively promoted wound closure in the HaCaT keratinocyte cell line model. The anti-inflammatory activity results clearly showed that when we used S. aureus as an inflammation-inducing agent and the A. aegerita aqueous extract in treatment, IL-6 levels reduced to the level of 4.56 pg/mL. The obtained data suggest that the tested mushroom extracts may serve as a source of bioactive compounds, with potential applications in the cosmeceutical, pharmaceutical and food industries. Furthermore, potential skin preparations carefully crafted with mushroom extract may help restore the skin's barrier function, decrease the probability of staph infections and minimize skin irritation.

Assessing dietary habits with validated questionnaires is crucial for achieving reliable results in health research. The aim of this study was the development and validation of a semi-quantitative food frequency questionnaire (FFQ) in an 18-30-year-old Serbian population. A total of 93 participants completed the FFQ and three 24 h dietary recalls (24 hR). Pearson and intraclass correlations between FFQ and 24 hR intakes were assessed and were de-attenuated and energy-adjusted. Bland-Altman plots were generated, and quintiles of energy, water, fiber, and macronutrient intake were analyzed with contingency tables. Adjustments for sex differences were included. The validity of the FFQ varied, with significant correlations for energy, carbohydrates, cholesterol, and vitamin B 12 , vitamin C and vitamin D. Misclassification rates were generally low. Bland-Altman plots indicated good agreement between methods. It can be concluded that the validated FFQ is a promising tool for dietary assessment in the Serbian population. Results for several nutrients align closely with previous studies. The new FFQ is a useful tool for dietary assessment in the Serbian population.

Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a "probable" relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns.

This study aimed to characterize mixtures of goat milk proteins and Agaricus blazei Murrill (ABM) extracts (aqueous, AE and polysaccharides, PE). The mixtures showed stable particles with ζ-potential more negative than -41.1 mV. The addition of AMB extracts to goat milk did not result in a significant particle size change, whereas their addition to heated goat milk significantly increased mean particle diameter (from 194 nm to 225 nm). Fourier Transform Infrared Spectroscopy (FTIR) showed that ABM extracts provoked changes in the secondary structure of goat milk proteins and interactions between polysaccharides and milk proteins predominantly via hydrogen and/or glycoside bonds and hydrophobic interactions. The milk protein profiles revealed proteolytic activity in mixtures with AE resulting in the formation of five new polypeptides. The different microstructures of mixtures with AE and PE were found by Scanning Electron Microscopy (SEM). A schematic representation of possible milk proteins-ABM extracts interactions has been given., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Blackthorn ( Prunus spinosa L.) fruit is bluish-black wild fruit traditionally used in nutrition and medicine. It is recently gaining attention as a functional food and an underutilized source of bioactive compounds for application in the food and pharmaceutical industry. This study aimed to assess the health-promoting potential of blackthorn fruits from Serbia by examining their chemical composition and in vitro biological activities. Phytochemical analysis of the blackthorn fruit extracts was performed using LC-DAD-ESI-MS. The total phenolic (TPC), total flavonoid (TFC), total anthocyanin (TAC) content, antioxidant capacity, and enzyme inhibitory activities were determined spectrophotometrically. The antimicrobial and prebiotic properties were tested using the broth microdilution method. Twenty-seven phenolics belonging to the classes of hydroxybenzoic and hydroxycinnamic acids derivatives, flavonoids, and anthocyanins were identified, with caffeoylquinic acid as the most abundant compound. Blackthorn extracts were characterized by notable TPCs, TFCs, and TACs, and free radical scavenging and reducing ability. The enzyme inhibitory effects (IC 50 = 0.43-2.16 mg/mL) were observed towards α -amylase, α -glucosidase, acetylcholinesterase, and tyrosinase. Blackthorn fruit extracts in a concentration-dependent manner (0.3-5 mg/mL) stimulated the growth of several probiotic microorganisms and their mixtures, especially the yeast Saccharomyces boulardii . Obtained results support further evaluation of the functional food potential of blackthorn fruit.

The rising popularity of dietary supplements as a part of self-care practice increases interest in monitoring their usage in the general and specific population groups. This study investigated the prevalence and patterns of dietary supplement use among Belgrade University undergraduate students and its variations across different academic study fields. Of the 914 online survey students, 55.7% used dietary supplements during the past year. Female gender, eating behavior, and academic field were significant predictors of dietary supplement use. For all students, the most commonly used dietary supplements were vitamins and minerals, alone or in combination. Magnesium, vitamin C, and B vitamins were the most frequently supplemented micronutrients. The reasons for using, place of purchase, and source of information regarding dietary supplements significantly varied among students of different fields of study. Adverse effects related to dietary supplement use, including gastrointestinal symptoms, skin flushing, dizziness, and heart palpitation, were reported in 4.5% of students. Insufficient knowledge about these products was self-reported by 16.5% of users, more common among non-medical students. Thus, public health interventions are needed to improve students' knowledge regarding rational and safe dietary supplement use.

Goji berries have long been used for their nutritional value and medicinal purposes in Asian countries. In the last two decades, goji berries have become popular around the world and are consumed as a functional food due to wide-range bioactive compounds with health-promoting properties. In addition, they are gaining increased research attention as a source of functional ingredients with potential industrial applications. This review focuses on the antioxidant properties of goji berries, scientific evidence on their health effects based on human interventional studies, safety concerns, goji berry processing technologies, and applications of goji berry-based ingredients in developing functional food products.

Since the fruits of Lycium L. species ( Fructus Lycii , goji berries) are promoted as a "superfood" with plenty of health benefits, there is extensive research interest in their nutritional and phytochemical composition. In the present study, the nutritional value, minerals, fatty acid composition, and bioactive compounds of L. barbarum L., red, yellow, and black goji berry ( L. ruthenicum Murray.) cultivated in Serbia were investigated. Antioxidant and antimicrobial properties of their methanol extracts were assessed. Red goji berry had the highest content of fats, dietary fiber, iron, total carotenoids, and 2- O -β-d-glucopyranosyl-l-ascorbic acid (AA-2βG). The yellow goji berry extract showed the highest level of flavonoids and the most prominent antimicrobial (especially against Gram-negative bacteria) properties. The highest total phenolic content and the most potent antioxidant activity were observed for the extract of black goji berry. Therefore, all goji berries could be a valuable source of bioactive compounds in the food and pharmaceutical industry.

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

Background: The purpose of this study was to examine the effects of alpha-lipoic acid (LA) supplementation on oxidative stress markers in patients with schizophrenia., Subjects and Methods: Eighteen (18) medicated patients with schizophrenia and 38 healthy controls received daily supplements of LA (500 mg/day) for three months. At baseline, 45th and 90th days of supplementation, venous blood collected for analysis of oxidative stress markers [superoxide anion (O2(•-)), thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP)] and antioxidative defense markers [superoxide dismutase (SOD), total sulfhydryl groups (-SH) and total antioxidant status (TAS)]., Results: Increased plasma TBARS, TAS, SH groups levels and SOD activity were found in schizophrenic patients compared to control group. LA supplementation significantly reduced TBARS, AOPP and improved TAS levels in healthy subjects, while there were no significant differences in patients group. SH groups increased after 45 days and decreased to baseline levels after 90 days of supplementation in the control group. SOD activity decreased significantly in patients group after 45 days and 90 days of supplementation. After initial rose SOD activity in control group, decreased to baseline levels found after 90 days., Conclusion: LA supplementation decreased lipid peroxidation and oxidative damage of proteins and improved non-enzymatic antioxidant capacity in healthy controls. No significant changes were observed on oxidative damage in patients with schizophrenia.

Background: The purpose of this study was to assess oxidative stress status parameters and their possible associations with traditional cardiovascular risk factors in patients with schizophrenia, as well as their potential for patient-control discrimination., Methods: Fasting glucose, lipid profile and oxidative stress status parameters were assessed in 30 schizophrenic patients with atypical antipsychotic therapy and 60 control subjects., Results: Malondialdehyde (MDA), pro-oxidant/antioxidant balance (PAB) and total anti-oxidant status (TAS) were significantly higher whereas total sulfhydryl (SH) groups were significantly lower in schizophrenic patients vs. control group. Higher serum PAB values showed an independent association with schizophrenia. The addition of PAB to conventional risk factors improved discrimination between healthy control subjects and patients., Conclusion: Increased oxidative stress and changed lipid profile parameters are associated in schizophrenic patients and may indicate risk for atherosclerosis. The serum PAB level may reflect the levels of oxidative stress in schizophrenia and improve discrimination of patients from controls.

The aim of this study was to determine the plasma selenium (Se), copper (Cu), and zinc (Zn) levels and to evaluate their possible association with metabolic syndrome (MetS) components in patients with schizophrenia. The study group consisted of 60 patients with schizophrenia and 60 sex- and age-matched healthy controls. Anthropometric measurements, blood pressure, and biochemical analysis of fasting blood were performed in all subjects. Patients with schizophrenia had significantly higher plasma Cu concentrations compared with controls (0.97 ± 0.31 vs. 0.77 ± 0.32 mg/L, p = 0.001). The plasma Cu concentration showed a positive correlation with plasma glucose and diastolic blood pressure in the patient groups (r s = 0.263, p < 0.05 and r s = 0.272, p < 0.05, respectively). The plasma Se level correlated positive with MetS score (r s = 0.385, p < 0.01), waist circumference (r s = 0.344, p < 0.05), plasma glucose (r s = 0.319, p < 0.05), and triglyceride concentrations (r s = 0.462, p < 0.001) in patients with schizophrenia. Plasma Zn did not correlate with any of the MetS components. These results suggest that alterations in plasma Cu and Se levels in medicated patients with schizophrenia could be associated with metabolic risk factors.