The primary aim of the current investigation was the Analytical progression and validation of a UV-spectrophotometric analytical approach for the quantification of Nirogacestat in both bulk and pharmaceutical dosage forms, in alignment with ICH regulatory standards. A straightforward, expeditious, reliable, and economically viable UV-spectrophotometric technique was established for the quantitative determination of Nirogacestat employing acetonitrile as the solvent medium. The absorbance of the analyte solution was recorded at 269 nm relative to a suitable blank. Method validation was performed pursuant with prescribed parameters, encompassing linearity, accuracy, precision and robustness. The λmax of Nirogacestat in acetonitrile was identified at 269 nm. The analyte demonstrated compliance with Beer-Lambert’s law across the concentration interval of 2.5–15.0 μg/mL, exhibiting a correlation coefficient(R²) of 0.999. The percentage recovery ranged from 99.3% to 100.1% reflecting substantial accuracy. Precision assessments resulted %RSD values below 2.0, substantiating both repeatability and intermediate precision. Robustness evaluations involving minor alterations in wavelength exhibited negligible deviation, thereby affirming reliability. Additionally, forced degradation experiments substantiated the stability-indicating characteristics. The delineated UV-spectrophotometric technique is straightforward, analytically sensitive, and reproducible. It is eminently suitable for routine quality assessment and quantitative evaluation of Nirogacestat in bulk drug substances and tablet formulations.
Sepsis is a complex, life-threatening disease characterized by multiple organ failure due to an abnormal systemic response to infection. Its multifaceted pathophysiology involves a dynamic balance linked pro-inflammatory and anti-inflammatory mediators, coagulation activation, and altered cellular functions. Although different kinds of regulated cell death (RCD) are implicated in sepsis pathogenesis, ferroptosis has emerged as an iron-mediated cell death. Molecular drivers of ferroptosis include iron accumulation, lipid peroxidation, production of reactive oxygen species (ROS), and inhibition of Glutathione peroxidase 4 (GPX4), eventually causing cell death. Current pre-clinical studies are aimed at modulating the ferroptosis pathway, and clinical studies are exploring the therapeutic strategies across diseases. The connection between sepsis and ferroptosis is bound by cellular abnormalities participating in several RCD mechanisms, including apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy. These cellular abnormalities encompass mitochondrial shrinkage, collapse of cristae, increased membrane density, activation of unfolded protein response, hydrolytic enzyme leakage, and enhanced lysosomal degradation. Additionally, genes associated with ferroptosis, such as Mitogen-Activated Protein Kinase 14 (MAPK14), Acyl-CoA Synthetase Long-Chain Family Member (ACSL4), Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), and GPX4, have altered expression during sepsis, which impacts both the susceptibility and the progression of ferroptotic cell death.
Plant sterols are naturally occurring bioactive compounds widely recognized for their cholesterol-lowering effects. This narrative review critically evaluates current evidence regarding the role of phytosterols in insulin resistance, glucose metabolism, and type 2 diabetes mellitus (T2DM). Literature was collected from PubMed, Scopus, and Google Scholar for studies Published between 2000 and 2024 using pre-defined keywords related to phytosterols, insulin resistance, and T2DM. Evidence from in-vitro and animal studies suggests that phytosterols may influence AMPK, PI3/Akt, and GLUT4 signaling pathways and may improve metabolic homeostasis. However, evidence from human clinical trials remains limited and in-consistent. Current findings strongly support the lipid-lowering benefits of phytosterols, where as their role in glycemic control requires further validation through well-designed clinical studies.
This study aims to investigate the effects of Vitamin D and EB1089 (seocalcitol), a synthetic vitamin D receptor agonist, on morphine-induced analgesia and the development of morphine tolerance in rats using thermal antinociceptive assays and plasma serotonin analysis. A total of 56 male Wistar albino rats weighing 240–260 g were used in the study. The rats were randomly assigned to 7 groups, with 8 rats in each group. Evaluation of antinociceptive activity was performed using the tail flick and hot plate methods. Serotonin levels in plasma were analyzed using the ELISA method. In the tail flick test, the morphine + vitamin D group exhibited significant analgesia compared to the control group. In the hot plate test both the morphine + vitamin D and morphine + EB1089 groups exhibited significant analgesia compared to both the control and morphine groups. Both the morphine tolerance + vitamin D and morphine tolerance + EB1089 groups showed a significant increase in pain threshold in the tail flick and hot plate tests compared to the control and morphine tolerance groups. This study demonstrates that vitamin D and EB1089 enhance the analgesic effects of morphine in rats and slow the development of morphine tolerance.
Furosemide is a loop diuretic widely prescribed for the management of edema and hypertension; however, its oral efficacy is limited by poor solubility and low permeability. According to the Biopharmaceutics Classification System, furosemide belongs to class IV, necessitating optimization at the preformulation stage to enhance its biopharmaceutical performance. This review aims to analyze various preformulation strategies that have been demonstrated to improve the solubility and oral bioavailability of furosemide through an extensive literature review of scientific publications from the past decade. The investigated approaches include particle size reduction, co-amorphous systems, micronization, solid dispersion, solvent evaporation, cyclodextrin complexation, pH adjustment, self-nanoemulsifying drug delivery systems, nanostructured lipid carriers, solid–liquid nanoparticles, nanosuspensions, and controlled precipitation methods. The review indicates that these strategies markedly enhance the dissolution rate and physical stability of furosemide through several mechanisms, such as increased surface area, amorphous phase formation, inclusion complexation, and maintenance of supersaturated states. Among the reviewed strategies, lipid-based and nanoscale delivery systems generally demonstrated greater improvements in oral bioavailability than conventional approaches, although direct comparisons should be interpreted with caution because of differences in study design, experimental conditions, and pharmacokinetic endpoints. Overall, physicochemical modification and nanotechnology-based preformulation strategies offer promising potential to overcome the solubility limitations of furosemide, thereby improving oral therapeutic efficacy and reducing interindividual pharmacokinetic variability.
Sleep disorders in children can negatively impact their development and quality of life. While melatonin is commonly used to manage these issues, there are no FDA-approved formulations specifically designed for children, and traditional tablet forms can be challenging for these patients. This study aims to develop a patient-friendly melatonin syrup formulation suitable for personalized pediatric therapies. Each teaspoon contains 1.0 mg of melatonin, allowing for flexible and precise dosing customized to individual patient needs. Melatonin content was quantified using a reversed-phase HPLC method with UV/Visible detector (HPLC-UV/Vis) ifadesi ‘with UV/Visible detector (HPLC-UV/Vis) that was developed and validated in line with ICH Q2(R1), demonstrating selectivity, linearity (1.0–30.0 μg/mL; R²=0.999), and intra- and inter-day accuracy and precision within 2%. Stability studies demonstrated that the syrup remains stable and retains its potency for at least seven days at room temperature. This syrup formulation enhances palatability and ease of administration, potentially improving therapeutic outcomes in children with sleep disorders through personalized treatment approaches. The syrup can be easily prepared using commercially available melatonin tablets in hospital pharmacies or home settings, using safe pediatric excipients.
Linagliptin is a dipeptidyl peptidase-4 inhibitor used to treat type 2 diabetes and is categorized as a BCS class III drug, having high solubility and low permeability, resulting in a very low bioavailability, 30%, of the drug. Microspheres have been formulated to increase the gastric retention time. The batches were formulated using a 32-full-factorial design of experiments, taking the concentration of ethyl cellulose, and speed of homogenizer as the factors, and % entrapment efficiency and particle size as the dependent parameters. The optimized batch, having 200 mg of ethyl cellulose and an 8000 rpm speed of homogenization, was formulated, which showed 80.3 % of the drug was released at the 8th hour. Mean particle size, % entrapment efficiency, and percentage yield of the optimized formulation were found to be 1.57 μm, 92%, and 96.99%. The kinetic model for the in vitro release of linagliptin microspheres was analysed, and results indicated that it followed the zero-order kinetic model based on the R² values.
Diabetic foot ulcer (DFU), a chronic complication of diabetes, is marked by delayed wound healing due to persistent inflammation and oxidative stress. Owing to its complex pathophysiology, DFU requires therapeutic agents capable of targeting multiple molecular pathways. Lawsone, a bioactive compound from Lawsonia inermis, possesses notable antioxidant and anti-inflammatory activities, yet its role in DFU management has not been fully explored. This study aimed to assess the multi-target therapeutic potential of lawsone using in silico tools. Drug-likeness was predicted through SwissADME, while SwissTargetPrediction was used to identify possible molecular targets of lawsone. DFU-associated genes were obtained from GeneCards and common targets were subjected to protein-protein interaction (PPI) analysis via STRING. Key hub genes were determined using Cytoscape. Functional enrichment, including Gene Ontology (GO) and KEGG pathway analysis, was performed using ShinyGO. Molecular docking through AutoDock was conducted to evaluate lawsone’s binding affinity with hub proteins. A total of 51 overlapping targets were found, with ten hub proteins such as ESR1, PTPN11 and PPARA implicated in crucial DFU-related processes. Docking results indicated favorable binding interactions. This study provides computational evidence for lawsone’s multi-target efficacy, supporting its potential role in modulating key pathways involved in diabetic wound healing.
Obesity and obesity-related dyslipidaemia are major contributors to global cardiometabolic risk. Polyphenol-rich functional foods have gained attention as supportive strategies for the regulation of lipid metabolism and adipose tissue function. Among these, Aronia melanocarpa (black chokeberry) is a rich source of anthocyanins and other bioactive polyphenols with potent antioxidant and metabolic properties. This review evaluates current experimental and clinical evidence on the effects of Aronia melanocarpa on obesity and lipid metabolism. Available data indicate that chokeberry polyphenols may improve lipid homeostasis by modulating adipogenesis, regulating key metabolic pathways, reducing oxidative stress and inflammation, and influencing gut microbiota. However, clinical findings remain heterogeneous due to variations in study design, dosage, and phytochemical composition, as well as the limited bioavailability of anthocyanins. Overall, Aronia melanocarpa appears to be a promising natural agent for the management of obesity and dyslipidaemia, however, further well-designed clinical studies using standardized preparations are required to confirm its therapeutic potential.
Medicinal cannabis is attracting increasing attention for its therapeutic potential in cancer treatment due to its ability to modulate key signaling pathways associated with tumor progression and cell death. Among various mechanisms, cannabinoids have recently been shown to trigger ferroptosis that is a regulated, iron-dependent form of cell death characterized by lipid peroxidation and glutathione depletion. This review focuses on the emerging role of cannabinoids in inducing ferroptosis in cancer cells. Cannabinoids, particularly non-psychoactive compounds such as cannabidiol (CBD), have been shown to disrupt redox homeostasis by suppressing the cystine/glutamate antiporter system Xc-, depleting intracellular glutathione, and inhibiting glutathione peroxidase 4 (GPX4) activity. These events lead to excessive lipid peroxidation and ultimately cause ferroptotic cell death. Furthermore, cannabinoids disrupt iron metabolism, promote ferritinophagy, and affect certain transcriptional regulators, making tumor cells more susceptible to ferroptosis. Cannabinoid-induced ferroptosis has been observed to be particularly selective in cancer cells, providing a strategic advantage in targeting treatment-resistant tumors. Despite encouraging preclinical evidence, studies directly linking cannabinoids to ferroptosis are still limited, and clinical data are lacking. Future research should focus on improving formulation strategies, identifying reliable ferroptosis biomarkers, and validating the clinical significance of these pathways in cannabinoid-based anticancer therapies.
Scirpus kysoor, has been used to treat various illnesses, but its effects on diabetes and cholesterol levels have not been scientifically proven yet. The study investigated the antihyperlipidemic and antidiabetic effects of HESK (hydroethanolic extracts of Scirpus kysoor) in high fat diet (HFD)with streptozotocin induced diabetic rats. Six experimental groups were designated. Group I received 0.9% NaCl, while Groups II–VI were administered HFD (3 ml/kg), Glimepiride (10 mg/kg), or 100, 200, and 400 mg/kg HESK respectively. With the exception of Group I, all rats were fed HFD for 56 days and made diabetic by a single intraperitoneal injection of STZ (35 mg/kg) on day 28. Biochemical markers like Glucose, Cholesterol, Triglycerides, ALP, ALT, AST, HDL, LDL and Total Protein were assessed. Anthropometric parameters, including Body weight, Food intake, AC/TC ratio, abdominal and thoracic circumference were measured. At last of the study, the levels of antioxidant parameters (LPO, CAT, SOD, GSH & total thiols) and the histopathology of the liver and pancreas were evaluated. Results showed HESK significantly reduced glucose, cholesterol, triglycerides, ALP, ALT, AST, and LDL, while increasing HDL and total protein levels (p
The genus Vincetoxicum Wolf (Apocynaceae: Asclepiadoideae), naturally distributed across Africa, Australia, Asia, and Europe, comprises approximately 140 species. Species within this genus have been used in traditional medicine to treat wounds, fractures, inflammation, and envenomations from snake, insect, and scorpions. Vincetoxicum is one of the most species-rich genera of the subfamily in Anatolia. Vincetoxicum fuscatum subsp. fuscatum is known as “dağ biberi, gâvur üzerliği, and gâvur biberi” in Turkey. This research focused on analyzing ethanol extract from seeds of V. fuscatum subsp. fuscatum, to assess its phenolic and flavonoid contents, antioxidant activity, and cytotoxic profile. Total phenolic and flavonoid contents, along with antioxidant activity, were studied using the Folin-Ciocalteu, AlCl3, and DPPH assays, respectively. Cytotoxicity was tested on HaCaT cell line using the MTT assay. The total phenolic and flavonoid contents and antioxidant activity were 7.42 ± 0.04 mg GAE/g seed; 3.08 ± 0.01 mg QE/g seed; and 27.3 ± 0.01% inhibition, equivalent to 0.26 ± 0.06 mM AAE/g seed, respectively. All tested concentrations of the extract (0.25-1 mg/mL) did not exhibit any cytotoxic effect on the HaCaT cell line. This is the first study to investigate the total phenolic and total flavonoid contents, as well as the antioxidant and cytotoxic activities of V. fuscatum subsp. fuscatum seeds.
Dimocarpus longan (longan) is a tropical fruit commonly cultivated in China, Vietnam, and Thailand. The pulp, seed, flower, twig, and pericarp of longan have been extensively studied but the peel is often discarded as waste and remain underexplored. The extracts of longan peel were prepared using green solvents (methanol, ethanol, and ethyl acetate). The phytochemical profile of the extracts was screened by the thin layer chromatography (TLC) analysis. The antibacterial activity of the extracts was determined by the disk diffusion method and Minimum Inhibitory Concentration (MIC). The TLC analysis showed that the ethyl acetate extract possessed the most phytochemicals (phenolic compounds, flavonoids, tannins and steroids) compared to the methanol and ethanol extracts. All the extracts exhibited comparable antibacterial activity against Bacillus cereus (B. cereus) where the diameters of inhibition zones were ~ 9.01-9.77 mm. The MIC values for methanol and ethanol extracts were 1 mg/mL, however, the MIC value of the ethyl acetate extract could not be determined because the high water content in the broth caused sample precipitation. In summary, the longan peel extracts show potential as natural antibacterial agents against B. cereus.
The 1,3,4-oxadiazole ring is a structurally stable and pharmacologically active scaffold widely explored in drug discovery. This study presents a practical synthetic approach for 2,5-diaryl-substituted 1,3,4-oxadiazole scaffolds and evaluates their antimicrobial and antibiofilm potential. A total of 14 novel compounds were synthesized and screened for antibacterial activity against four clinically relevant bacterial strains: Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (NCTC 13846), and Salmonella enterica (RSKK 04059). Minimum inhibitory concentrations (MICs) were determined in micromolar (μM) ranges, and several compounds demonstrated promising antibacterial effects. Among them, compounds 11h and 11i were selected for further evaluation of antibiofilm activity. Both compounds significantly inhibited biofilm formation by S. aureus, E. faecalis, and S. enterica, even at concentrations below their MIC values. A dose-dependent inhibition profile was observed, indicating potential utility in targeting bacterial biofilms at low doses. Interestingly, no antibiofilm activity was observed against E. coli NCTC 13846; instead, biofilm formation appeared to increase at certain concentrations. In summary, the synthesized 1,3,4-oxadiazole derivatives, particularly 11h and 11i, exhibited promising antimicrobial and antibiofilm activities, indicating their potential as core scaffolds for the design of new therapeutic agents targeting resistant bacterial strains.
Phytosomes are innovative vesicular drug delivery systems designed to improve the therapeutic effectiveness of plant-derived bioactive compounds. They form stable molecular complexes through specific interactions between phytoconstituents and natural phospholipids, resulting in improved solubility, permeability, and stability. This review is intended to provide a comprehensive scientific evaluation of phytosomes, focusing on their physicochemical characteristics, formation mechanisms, preparation methods, characterization techniques, therapeutic applications, and existing limitations. Data from peer-reviewed literature were analyzed, covering formulation strategies such as solvent evaporation, anti-solvent precipitation, rotary evaporation, and ether injection. Characterization techniques like X-ray diffraction, nuclear magnetic resonance, and microscopy confirm complex formation and assess structural integrity and stability. Preclinical studies demonstrate that phytosomes significantly enhance bioavailability and pharmacological effects in various disease models, including cancer, diabetes, hepatic injury, and neurodegenerative disorders. Formulations based on Geophila repens, Cedrus deodara, and Ginkgo biloba showed superior efficacy compared to non-complexed extracts in both in vitro and in vivo models. The successful commercialization of several phytosome-based products further supports their translational potential. While the technology shows promise in overcoming bioavailability challenges in herbal therapeutics, further work is needed to address standardization, scalability, and regulatory validation to ensure broader clinical application.
This study developed and evaluated silver sulfadiazine (SSD)-loaded hydrogel films based on sodium alginate (SA) and basil seed mucilage (BSM) for controlled topical delivery. Films were formulated by varying SA (800–1000 mg) and BSM (50–200 mg) with calcium chloride (CaCl2) (5–15%) as the crosslinker and propylene glycol (15% w/w) as a plasticizer. The optimized film (900 mg SA, 100 mg BSM, 10% CaCl2, 30 min) was selected for its superior integrity and swelling. Attenuated Total Reflectance–Fourier Transform Infrared Spectroscopy (ATR–FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), and X-ray Diffraction (XRD) confirmed SSD compatibility and uniform polymer dispersion. The optimized film exhibited high swelling (~38 g/g), moderate thickness (~609 μm), excellent flexibility (~252 folds), optimum tensile strength (0.454 kg/cm2) and good surface wettability (~48° contact angle), reflecting balanced hydrophilicity and mechanical strength. In vitro release followed Fickian diffusion (Korsmeyer–Peppas n < 0.45), while additional evaluations confirmed appropriate water vapor transmission, microbial barrier properties, and hemocompatibility ( < 5% hemolysis), supporting its biocompatibility. Overall, SA–BSM hydrogel films show strong potential as wound dressings, offering a stable, biocompatible matrix for sustained SSD delivery. However, as the study was limited to in vitro evaluations, further in vivo, stability, wound healing, and mechanical studies are warranted.
Liver injury is closely associated with changes in gut microbiota, leading to the release of bacterial endotoxins such as lipopolysaccharide (LPS). These endotoxins interact with toll-like receptors (TLRs), especially TLR4, expressed on liver immune cells. Although LPS is known to play a crucial role in liver pathogenesis, the progression of liver dysfunction following LPS exposure remains insufficiently explored. This study aimed to develop and characterize a rat model of LPS-induced liver injury. Animals were divided into five groups (n=6). Group I received saline (control), Group II received alcohol (1.24%, 0.4 ml), and Groups III–V were sensitized with increasing doses of LPS (1 μg, 10 μg, and 100 μg/rat, i.p.) for 10 days and challenged on day 21, with LPS (10 μg/rat, i.p.) which markedly increased the liver parameters. Biochemical parameters like SGPT, SGOT, ALP, bilirubin, total protein, globulin, and albumin were evaluated at multiple time points. Groups III and IV showed significant increased in AST, ALT and ALP level. The protein levels were significantly reduced in alcohol treated group. Bilirubin level was significantly increased in LPS treated and alcohol treated groups around 28th day of treatment, which indicates liver injury. This model demonstrates a reproducible method to study LPS-induced liver damage.
Diabetes is one of the most common chronic diseases and its incidence and prevalence have been increasing in recent years. Moreover, many comorbidities can be observed in addition to diabetes. For this reason, medicinal plants have been an important complementary treatment option for individuals with diabetes from past to present. However, as in every disease, the correct use of medicinal plants in diabetes is important. Failure to do so may worsen the course of the disease, cause side/adverse effects and lead to herb-drug interactions. This review aimed to identify antidiabetic medicinal plants comprehensively and to describe the most commonly used ones in detail. When the studies in the literature were evaluated, it was determined that many medicinal plants with antidiabetic effects have been used from past to present, but the potential mechanism of activity, positive/negative effects, dosages, and plant-drug interactions of many of them have not been fully revealed. Further research is needed, as the incorrect and unknowing use of these medicinal plants can worsen the course of the disease.
Free radicals and nitric oxide play an important role in the pathogenesis of Myoglobinuric Acute Renal Failure (mARF). Herein, we aimed to investigate the effects of Ferula elaeochytris on the oxidative-antioxidant system and nitrosative stress in experimental mARF. In our study, 56 Sprague-Dawley rats, equally divided in seven groups, were used as model organisms of experimentally induced mARF. A disease model of mARF was established with 50% glycerol in all groups except one. Moreover, 40 mg/kg and 80 mg/kg of F. elaeochytris root extract were administered intragastrically before and after model creation. The following were investgated in the kidney tissue: serum urea nitrogen, urea, creatinine, sodium and potassium levels of rats in all groups; urinary urea and creatinine levels; MDA, SOD, GPx, CAT, NO and nitrotyrosine parameters. In addition, histological changes in the kidney were recorder with electron microscopy. Significant changes were observed in the CAT, GPx and MDA values of all groups compared to the control group. Electron microscopy observations also supported these findings. Herein, we provide evidence regarding the limited protective and curative effects of Ferula elaeochytris on mARF through reduction of the oxidant/nitrosative stress.
Transdermal drug administration is a method of administering medication through the skin that is non-intrusive, offering an innovative and hopeful alternative to traditional oral and injection methods. Advancements in skin penetration technology have enabled the transdermal administration of various anticancer medications, including lipophilic or hydrophilic compounds, offering a new approach to cancer treatment. Research has explored innovative platforms for cancer treatment, such as erythrocytes, vesicles, and exosomes. The most efficient approach is the transdermal drug delivery system. This review investigates various transdermal delivery techniques beyond the pharmaceutical sector in relation to cancer treatment. Techniques include iontophoresis, electroporation, sonophoresis, microneedles, transdermal patches, or vesicular systems like liposomes, niosomes, transferosomes, ethosomes, transethosomes, nanoparticles, carbon nanotubes, quantum dots, as well as nanofibers, which have been used to improve transdermal distribution and their use in cancer treatment. Additionally, a roadmap is presented to guide development strategies, highlighting the multiple applications of transdermal drug administration systems for cancer therapy.
