PH-responsive carbohydrate polymers have gained significant attention as promising candidates for next-generation oral drug delivery systems. This review focuses on the use of pH-sensitive carbohydrate polymers as a platform for controlled drug delivery. The unique ability of these polymers to undergo a conformational or structural change in response to specific pH ranges makes them ideal for targeted drug release. The gastrointestinal tract, with its distinct pH environments ranging from the highly acidic stomach to the neutral small intestine, presents a perfect scenario for these intelligent delivery systems. The design principles of these systems, including the chemical modification of natural carbohydrate polymers and the synthesis of new pH-sensitive materials, are explored. Furthermore, this review summarizes recent advancements and challenges in the application of carbohydrate polymers for oral drug delivery, particularly in enhancing drug bioavailability, protecting acid-labile drugs, and enabling site-specific release in the colon. The review concludes by highlighting the immense potential of these biocompatible and biodegradable materials in developing advanced, patient-friendly pharmaceutical formulations. In addition, the primary limitations of these materials are discussed with respect to enzymatic degradation, scaling up, cost-effectiveness, and regulatory approval.
The rise of antimicrobial resistance (AMR) has highlighted the need for exploration of alternative therapeutic agents, including medicinal plants. This study investigates the antibacterial potential, phytochemical composition, and toxicity of Azadirachta indica leaf extracts, along with their interactions with conventional antibiotics. Extracts prepared in water (AQ), methanol (MeOH), and ethyl acetate (EtOAc) were evaluated for growth-inhibitory effects against a range of bacterial species, including drug-resistant isolates, through both disc diffusion and microdilution methods. Zone of inhibition (ZOI) measurements ranged from 7 to 10 mm, while minimum inhibitory concentration values varied between 2938 and 5875 µg/mL for AQ extracts, and between 1175 and 4700 µg/mL for MeOH extracts. Notably, EtOAc extracts did not inhibit bacterial growth in either assay. Fractional inhibitory concentration (FIC) analysis revealed additive interactions of extracts with β-lactam antibiotics (penicillin G, oxacillin, amoxicillin) and protein synthesis inhibitors (tetracycline, chloramphenicol), particularly against Bacillus cereus, Staphylococcus aureus, and Shigella spp., suggesting a potential role as antibiotic adjuvants. However, antagonistic interactions were also observed in combinations containing gentamicin and polymyxin B. Liquid chromatography–mass spectrometry (LC-MS) analysis confirmed the presence of phytochemicals, including flavonoids, tannins, and phenolics, which are known for their antimicrobial properties. Evaluation of extract safety using brine shrimp ( Artemia franciscana) assays revealed no toxic responses. To ensure their safety for therapeutic applications, future toxicity evaluations should be conducted on mammalian cell lines to confirm these findings. Future research should focus on isolating bioactive compounds from the extracts, elucidating their mechanisms of action, and optimizing extract-antibiotic formulations to combat resistant bacterial infections effectively.
Darjeeling tea ( Camellia sinensis var. sinensis) is recognized for its unique aroma and taste, associated with mood and cognitive enhancement. However, the underlying neurochemical mechanisms remain unclear. The present study investigates the potential interaction of Darjeeling tea’s volatile aroma compounds with glutamate receptors (GluRs), the predominant excitatory receptors in the central nervous system (CNS). We hypothesized that these compounds target GluRs to elicit their effects. An in silico approach was employed to analyze the physicochemical properties, bioactivity scores, and toxicity profiles of the aroma compounds. Subsequently, molecular docking simulations were performed using the retrieved 3D structures of relevant GluRs to predict the binding affinity of selected compounds exhibiting high bioactivity, drug-likeness, and bioavailability, and identify key amino acid residues within the receptor binding pockets. Our findings revealed α-ionone and safranal as prominent ligands exhibiting strong binding interactions. Among metabotropic GluRs, mGluR1 (IEWK), GluR5 (3FUZ), and GluR6 (3G3F) showed the highest affinity. Ionotropic receptor subtypes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (2WJW) and N-methyl-D-aspartate receptor (7EOR) also displayed significant binding scores, where greater structural dynamics were found in metabotropic GluRs on ligand binding compared to ionotropic subtypes. Given that inhalation via the nasal passage is a primary exposure route and the presence of GluR-expressing cells along this pathway, the high bioavailability of α-ionone and safranal suggests their potential to interact with neuroglial cells and subsequently influence CNS neurons and microglia/ macrophages. In conclusion, the identified binding of Darjeeling tea’s aromatic ligands and GluRs offers a promising framework for elucidating the mechanisms underlying the tea’s effects on mood, psychological states, and immune-physiological responses.
Alzheimer’s disease (AD) pathology involves several pathways, with oxidative stress and inflammation among the major drivers. This study employs an animal model to evaluate the effects of treadmill exercise and D-ribose- L-cysteine (DRLC) on aluminum chloride (AlCl3)-induced AD. Seventy adult male Wistar rats (150–200 g) were randomized into seven groups (𝑛=10), including a control and six experimental groups: (i) AlCl3-only; (ii) AlCl3 + DRLC; (iii) AlCl3 + exercise; (iv) AlCl3 + DRLC + exercise; (v) DRLC-only; and (vi) exercise-only. A modified rodent treadmill apparatus was used for the exercise regimen, and AlCl3 and DRLC (100 mg/kg each) were prepared freshly for every administration. Y-maze and open field tests were used to evaluate the neurotoxic effects of AlCl3 on working and spatial memory. Oxidative stress markers, neurotransmitter levels, neuroinflammatory markers, and immunohistochemical analysis were also conducted to assess the impact of AlCl3 and the treatments on the hippocampus and prefrontal cortex. Results indicate that AlCl3 administration led to a decrease in neurobehavioral performance, monoamine neurotransmitter levels, and antioxidant parameters, with a corresponding increase in oxidative stress and neuroinflammatory markers. The deleterious effects of AlCl3 were also evident in the hippocampus and prefrontal cortex of the rats, contributing to AD-like pathology, as indicated by neurodegeneration. However, combined DRLC supplementation and treadmill exercise attenuated AlCl3-induced behavioral, biochemical, and histopathological alterations, restoring several outcomes toward control levels. In conclusion, the combined approach of exercise and DRLC proved to possess multiple therapeutic benefits in relieving AD symptoms due to their neuroprotective properties.
Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are reported to have features intermediate between those of fetal and adult mesenchymal cells. Hence, UC-MSCs were cocultured with chondrocytes and Schwann cells to induce differentiation because of their flexible differentiation potential. UC-MSCs were obtained from umbilical cords, and cells at the second passage were used in the experiments. Atelocollagen sponge was used as the scaffold for coculture; a horizontal, interactive coculture plate with a filter (pore size, 0.6 μm) was placed between the connected vessels. UC-MSCs were cocultured separately with chondrocytes and Schwann cells, and culture alone served as a control. Five weeks after induction of differentiation, each specimen was evaluated histologically. In the specimens cocultured with chondrocytes and the controls, cartilage tissues were detected using hematoxylin-eosin and toluidine blue staining. Cells positive for the S100 protein were detected in the specimens cocultured with Schwann cells, but not in the controls. UC-MSCs were easily induced to differentiate into chondrocytes and neural cells by coculture. This indicates that continuously shared humoral factors were effective in inducing differentiation of UC-MSCs. Thus, coculture may serve as a potentially useful technique for tissue regeneration using MSCs.
Obesity is a complex systemic condition with significant sexual dimorphism, increasing the risks of disorders such as type 2 diabetes mellitus, arterial hypertension, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, premature cardiovascular disease, and certain types of cancers. A recent publication by Christaki et al. on the comprehensive overview of obesity management in Innovative Medicines and Omics highlights the multifactorial nature of obesity, as well as the importance of lifestyle changes, alongside pharmacological treatments and bariatric surgery. This commentary advocates for precision medicine strategies to effectively address the challenges posed by obesity. By highlighting the potential health and economic benefits of reducing obesity, we call for a holistic approach that integrates behavioral, medical, and policy interventions. We also identify research gaps, suggesting that future studies explore endocrine connections in obesity and assess endoscopic techniques targeting the duodenum as adjunct therapies in the context of tailored care.