In traditional medicine, Argemone mexicana L. (Papaveraceae) is used by Indian and Bangladeshi practitioners to treat jaundice and liver ailments. Despite its widespread use, its hepatoprotective activity lacks scientific validation in HepG2 liver cell models. This study evaluated the protective effects of methanolic extract of A. mexicana (MEAM) against paracetamol-induced hepatotoxicity in HepG2 cells. Antioxidant activity were assessed via DPPH, ABTS, lipid peroxidation, and ferricyanide assays. Cytoprotective effects were evaluated using MTT, LDH, AST, ALT, and inflammatory markers (TNF-α, IL-1β), along with oxidative stress indicators (SOD, GSH, GPx, MDA). LC–MS analysis was used to identify bioactive compounds in the MEAM. In silico molecular docking studies with Schrödinger software further examined the interaction of identified bioactive compounds with PPAR-α and TGF-β1 to explore their potential hepatoprotective mechanisms. MEAM exhibited strong antioxidant activities (IC₅₀: DPPH- 92.3, ABTS- 93.7, lipid peroxidation- 43.2 µg/mL). In the MTT assay, MEAM significantly (p < 0.05) increased HepG2 cell viability compared to the paracetamol-treated group. It also elevated antioxidant markers (SOD, GSH, GPx) and reduced MDA levels relative to the positive control. MEAM restored cellular architecture in a dose-dependent manner, similar to silymarin. Additionally, it significantly lowered AST, ALT, TNF-α, and IL-1β levels, approaching normal control values. In silico analysis identified reticuline and oxyberberine with the highest docking scores to PPAR-α and TGF-β1. MEAM showed significant in vitro hepatoprotective activity, supporting its traditional use. Hepatoprotective potential of Argemone mexicana L. root methanol extract: LC–MS profiling, molecular docking and protection against paracetamol-induced toxicity in HepG2 cell lines.

Prokinetic agents are drugs used to enhance gastrointestinal motility and treat disorders such as Gastroesophageal Reflux Disease (GERD) and gastroparesis. pH-dependent release systems offer targeted drug delivery, allowing prokinetic agents to be released specifically in desired regions of the gastrointestinal tract. This optimizes drug efficacy and minimizes systemic side effects. Gastroretentive formulations enable sustained drug release, which is particularly beneficial in conditions requiring prolonged gastric residence time, such as gastroparesis. Nanoparticles have emerged as promising carriers for improving prokinetic agent delivery and enhancing drug stability, solubility, and absorption. These nano-systems protect drugs from degradation, leading to improved bioavailability and controlled drug release. Furthermore, incorporating mucoadhesive technologies promotes prolonged drug-mucosa interactions, facilitating enhanced drug absorption and reducing dosing frequency. These recent advancements have the potential to revolutionize the oral drug delivery of prokinetic agents, offering improved therapeutic outcomes, enhanced patient compliance, and reduced side effects. However, scalability, biocompatibility, and safety challenges warrant further investigation and validation through preclinical and clinical studies. This review highlights recent advances in oral drug delivery systems for prokinetic agents, focusing on innovative approaches such as pH-dependent release, gastroretentive formulations, nanoparticles, and mucoadhesive technologies. In conclusion, integrating advanced oral drug delivery systems for prokinetic agents presents a promising avenue for managing gastrointestinal disorders. Continued research and collaboration among academia, industry, and healthcare professionals are crucial to unlocking the full potential of these innovations and ultimately translating them into clinically effective treatments for patients.

This study aimed to develop and optimize a preservative-free, controlled-release nanofiber formulation of loteprednol etabonate (LE) using polycaprolactone (PCL) for effective management of corneal inflammation. The objective was to minimize the challenges of limited solubility, poor ocular retention, and premature drug clearance while enhancing therapeutic efficacy. LE polycaprolactone nanofibers (LE-PCL-NF) were fabricated by electrospinning and optimized using polymer concentrations of 10-16% w/v. The optimized 14% PCL solution at a 1 mL/h flow rate and 15 kV yielded bead-free, uniform nanofibers with an average diameter of 210 +/- 17 nm. Solubility of the drug increased similar to 4-fold (i.e., 7.25 mu g/mL to 29.32 mu g/mL). The drug release results show that 50% of the drug was released within 6 h and 82% over 72 h, compared to pure LE, which shows only 32% release. Ex vivo corneal permeation data showed similar to 2.40-fold increase in permeation in 24 h as compared to the pure drug. HET-CAM and in vivo irritation tests confirmed safety and compatibility of the prepared formulation. LE-PCL-NF showed higher corneal retention (24 h) and maintained therapeutic levels in tear fluid for 72 h, unlike pure LE, which cleared within 6 h. In vivo efficacy studies reflect a significant reduction in redness and inflammation (p < 0.001), with eyes in the LE-PCL-NF-treated group appearing comparable to negative controls. LE-PCL nanofibers successfully enhanced solubility, sustained release, corneal retention, and anti-inflammatory efficacy while ensuring safety. These findings highlight their potential as a novel ocular delivery system for corneal inflammation.

The present study reports the development and evaluation of a localized re-dispersible mucoadhesive gargle (RMG) formulation of azithromycin (AZM) to mitigate secondary complications associated with bacterial throat infections with the potential to reduce the risk of antimicrobial resistance. The formulation was prepared using optimized pharmaceutical excipients, incorporating glycyrrhizin as a natural sweetener and multifunctional bioactive agent with proven anti-inflammatory, expectorant, and antitussive properties. The inclusion of glycyrrhizin was specifically rationalized based on its local mucosal anti-inflammatory action and its ability to support reflex-mediated cough modulation and mucus clearance at the oropharyngeal site. Re-dispersible granules were developed via wet granulation method and optimized using a Design of Experiments (DoE) approach. FTIR and DSC analyses confirmed the absence of significant interactions between the drug and excipients. The optimized formulation showed excellent drug loading (99.73

Introduction: Coronavirus disease 2019 (COVID-19) represents a significant global public health threat, with heightened morbidity and mortality observed among immunocompromised populations due to their impaired immune responsiveness and increased susceptibility to severe infection. Vitamins A, C, D, E, and the B-complex vitamins, as well as zinc, selenium, magnesium, and copper, are micronutrients needed to support a proper immune response against viral infections. This study aims to highlight the role of these micronutrients in modulating immune responses and their potential contributions to the prevention, management, and recovery from COVID-19. Methods: In this study, Google Scholar, PubMed, and ScienceDirect were utilized for the literature search. Articles on human research in English that focused on the immunological or clinical significance of micronutrients in viral infections, specifically COVID-19, were considered. Articles with poor methodological clarity, non-human studies, duplicates, editorials, and articles that were not clear on the methods used were excluded. Results: The evidence reviewed indicates that restricted diets due to food allergies lead to micronutrient deficiencies, which are associated with increased susceptibility to infections and worse COVID-19 outcomes. Increased micronutrient intake or supplementation was associated with a better immune phenotype, clinical recovery, and lower disease severity. Discussion: The positive impact of micronutrients is explained by the fact that they play the immune- regulating, antioxidant defense, inflammatory control, and antiviral defense functions. A lack of them can impair the immune system and accelerate disease progression in COVID-19. Conclusion: Properly balanced consumption of micronutrients can be an effective complement to common treatments to enhance the immune system, hasten recovery, and even reduce the severity of COVID-19.

Flavonoids, a diverse class of plant-derived polyphenolic compounds found in fruits, vegetables, and medicinal herbs, have gained considerable attention for their chemopreventive and anticancer properties. A key mechanism underlying their therapeutic potential is the modulation of DNA topoisomerases, enzymes essential for DNA replication, transcription, and recombination. Inhibition of topoisomerase I and II induces DNA damage, replication stress, and apoptosis in rapidly proliferating cancer cells. Flavonoids such as quercetin, kaempferol, myricetin, and epigallocatechin-3-gallate (EGCG) act as topoisomerase poisons or catalytic inhibitors by stabilizing the enzyme-DNA cleavage complex, leading to DNA strand breaks. Additionally, their pro-oxidant properties can enhance reactive oxygen species (ROS) generation, further amplifying DNA damage in tumor cells. Structural modifications of flavonoid scaffolds have improved enzyme selectivity, cellular uptake, and anticancer efficacy across various cancers, including leukemia, breast, colon, and lung cancer. Preclinical studies also highlight their synergistic potential with conventional chemotherapeutics, contributing to reduced drug resistance and toxicity. However, challenges such as poor bioavailability and metabolic instability remain. Advances in nanocarrier-based delivery and targeted therapeutic strategies may enhance their clinical translation as promising anticancer agents.

The global escalation of Multidrug-Resistant (MDR) bacterial infections poses a serious and growing threat to public health, contributing to increased morbidity, mortality, and substantial economic burden worldwide. The widespread and often indiscriminate use of antibiotics in clinical and agricultural settings has accelerated the emergence of resistance, significantly diminishing the efficacy of conventional antimicrobial therapies. This pressing challenge necessitates the exploration of alternative sources for novel antibiotics. Marine ecosystems-renowned for their immense biodiversity and ecological complexity-have gained attention as a rich and largely untapped reservoir of bioactive natural products with potent antimicrobial activity. Marine organisms, such as sponges, tunicates, algae, and bacteria and fungi derived from marine sources, produce structurally diverse and pharmacologically active metabolites, including peptides, polyketides, alkaloids, terpenoids, sterols, lactones, and halogenated compounds. Many of these marine-derived molecules possess unique chemical scaffolds and novel mechanisms of action, offering the potential to circumvent existing resistance pathways. Some compounds have shown promising activity against MDR pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii. However, challenges such as low natural abundance, difficulty in cultivation, and structural complexity have limited their clinical translation. Recent advancements in marine biotechnology, genomics, metagenomics, and synthetic biology have opened new avenues for the discovery, biosynthesis, and structural optimization of these compounds. These innovative approaches not only facilitate sustainable production but also enhance the pharmacological properties.

Oxy-Berberine (OBBR) is a metabolite of berberine (BBR) an isoquinoline alkaloid with promising hepatoprotective activity. But due to its lower aqueous solubility, and less retention time at site of action its clinical translation is limited. The present study aimed to develop and characterize a novel OBBR and ascorbic acid co-crystal (OBACC) incorporated in collagen microspheres (OBACC-CMPs) to enhance the solubility, release and hepatoprotective activity of OBBR. In-vitro solubility study showed that 1.70-fold higher solubility of OBACC as compared to the plain drug in aqueous media. Further, FT-IR, DSC, and XRD are carried out to investigate the drug, polymer, and excipients interactions. The morphology study by scanning electron microscope showed porous and spherical shape of microsphere at a size range of 5 μm. In-vitro drug release study revealed the controlled release manner of OBBR for 6 h at the site of action and release kinetics followed Korsemeyar-Peppas model. The in-vitro cell internalization study ensures the higher cellular uptake for 6 h as compared to the control and good cytocompatibility was observed at higher dose of microspheres in HepG2 cell line. In-vivo study emphasized the effectiveness of OBACC-CMPs on liver marker enzymes, proteins, lipid profile, cytokines and oxidative markers as compared to the PCM induced toxicity in rat model. Also, a prolonged accumulation of OBBR for 16 h was observed in bio-distribution study of OBACC-CMPs. Furthermore, the study highlights the OBACC-CMPs promising, safe and effective application for hepatoprotective and liver targeted applications. Co-crystal formation with ascorbic acid enhanced oxy-berberine’s aqueous solubility upto 1.70-fold. OBBR possessed controlled release for 6 h after micro-encapsulation with collagen biopolymer. OBACC-CMPs showed higher liver accumulation upto 16 h as compared to the pure drug.

Cancer remains a major cause of global morbidity and mortality, with rising incidence and limited effectiveness of conventional therapies due to systemic toxicity, adverse effects, and multidrug resistance. These limitations underscore the need for safer, targeted, and biologically effective therapeutic alternatives. Phytochemicals, naturally occurring com-pounds such as flavonoids, alkaloids, terpenoids, and polyphenols, have garnered consider-able attention due to their broad-spectrum anticancer activities and favorable safety profiles. This review assesses the therapeutic potential of phytochemicals in cancer prevention and treatment, focusing on their molecular mechanisms, pharmacological relevance, and translational applications. A comprehensive literature survey of peer-reviewed articles, clinical studies, and database reports (2015-2025) was conducted using PubMed, Scopus, Science Direct, and Web of Science with search terms including "phytochemicals," "plant-derived compound", "cancer", "tumor", "anticancer activity," "molecular mechanisms," "chemoprevention," "combination therapy," and "chemotherapy" with Boolean operators. Phytochemicals demonstrated significant anticancer effects by inhibiting cell proliferation, inducing apoptosis, suppressing angiogenesis, and modulating key oncogenic pathways, such as PI3K/Akt/mTOR, MAPK/ERK, and NF-κB. Clinically approved phytochemical-based drugs, including paclitaxel and vinblastine, validate their therapeutic relevance, while com-pounds such as curcumin and resveratrol show encouraging outcomes in ongoing studies. Synergistic interactions with conventional chemotherapeutics further enhance their thera-peutic potential. Overall, phytochemicals exert multi-targeted actions regulating oxidative stress, inflammation, and cell survival pathways, offering advantages of reduced toxicity and enhanced efficacy. However, challenges such as poor solubility and low bioavailability limit their clinical translation. Continued efforts toward advanced formulations and robust clinical validation are essential to advance their integration into modern cancer therapeutics.

Objectives:Subclinical endometritis in cattle is still a problem that has a detrimental effect on dairy production and fertility. Traditional intrauterine or systemic antibiotic treatments frequently result in suboptimal uterine drug levels, encourage resistance, and increase the possibility of drug residues in food items. The current study aimed to treat subclinical endometritis in repeat breeders by creating and testing an ofloxacin (Ofx)-loaded mucoadhesive polyvinyl alcohol/chitosan nanofiber using the electrospinning technique. Materials and Methods:The process constants were optimised using a central composite design to create a uniform nanofiber with maximum mechanical properties. Furthermore, in vitro (drug release, antibacterial activity), ex vivo (mucoadhesion and retention), and in vivo (endometrial cytology and plasma drug concentration) parameters were evaluated. Results:The scanning electron microscopy image of Ofx nanofiber suggests a diameter of 190-210 nm and tensile strength of 1.33 tensile strength with an entrapment efficiency of 97.54 ± 0.89%. Ofx delivered via nanofiber exhibited sustained release of Ofx up to 216 hours. Ex vivo assessments demonstrated stronger adherence and higher retention, while in vitro studies showed no cytotoxic effects. In vivo studies on the cattle suggested suitability for localized intrauterine administration. These findings indicate that encapsulation of Ofx in nanofibers stabilises the formulation and offers enhanced treatment efficiency compared to a conventional treatment regimen for subclinical endometritis in repeated breeders. Conclusion:Ofx-loaded nanofibers offer a novel and promising localized and mucoadhesive drug delivery approach for subclinical endometritis in cattle. Future research must prioritise further in vivo validation, long-term reproductive effects, and resistance management to translate into practical veterinary uses.

Malaria is a parasite-borne infectious disease faced with the major challenge of emerging resistance against front-line therapeutic agents like artemisinin and derivatives that heavily impact therapeutic outcomes. Hence, an alternative approach is necessary to manage malaria more effectively. Withaferin A (WS-3) is a well-known bioactive phytocomponent from Withania somnifera for its ROS-mediated anticancer activity. In the current experiment, the ROS-generating potential was compared to that of artesunate (Art), known for its ROS-mediated antimalarial activity. The flow cytometry-based analysis showed that an equal concentration (50 ppm) of WS-3 generated a comparable amount of ROS as Art. Further, the result was aligned with the in-vitro haemolysis activity. Hence, fine-tuning the combinations (WS-3 and Art) may improve the ROS generation capability. Further, an in-silico screening model for the molecular target of WS-3 was deployed against 112 molecular antimalarial targets. Based on the primary molecular docking study, WS-3 showed higher docking scores for glucose transporters (GLUT-1, glucose importer, and Plasmodium falciparum hexose transporter) and key metabolic enzymes (hexokinase and lactate dehydrogenase) than the standard drug molecules. Considering its combined ROS-inducing potential and computationally inferred targeting of glucose uptake and metabolic enzymes, WS-3 represents a promising molecule for integration into artemisinin-based combination strategies in preclinical antimalarial research.

Breast cancer is the most prevalent cancer in women worldwide and a major contributor to cancer-related death. It has been established for decades that natural bioactive compounds are a crucial source for developing novel anticancer drugs. However, their poor targeting, limited solubility and bioavailability, and instability hinder the effectiveness of treatment. With advancements in nanotechnology, nanomedicine delivery systems have emerged as viable approaches to enhance drug bioavailability and therapeutic effectiveness, with natural polymer-based drug carriers gaining significant attention for breast cancer treatment. Chitosan's distinct physicochemical characteristics, biocompatibility, and low immunogenicity make it a popular choice for carrier materials in nanomedicine delivery systems. Their desired qualities include the extent of chemical modification, controlled drug release, surface flexibility, non-toxicity, enhanced stability, cellular uptake, anticancer drug solubility, modulation of release kinetics, and biodistribution. This review aims to illustrate current concerns regarding breast cancer treatment, highlighting the untapped potential of natural bioactive compounds while promoting the latest developments of using chitosanbased nanocarriers to deliver natural bioactive compounds. Finally, this review spotlights the limitations of existing research and the futuristic prospects in this emerging field. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

The nanofibers based on hyaluronic acid (HA) have been considered as the promising platform in the mucosal and skin delivery of drugs due to its distinctive physicochemical, biological, and biomimetic characteristics. HA is a naturally occurring glycosaminoglycan which is biocompatible, biodegradable, mucoadhesive and has high hydration capacity and is ideally suited to local therapeutic delivery through the epithelial barriers. HA nanofibers electrospun have a high surface area, tunable porosity, and the potential to deliver a wide range of therapeutic molecules, including small molecules, biologics, probiotics, and growth factors, which allows them to release drugs in a controlled and targeted manner. Their recent progress is shown to be effective in the treatment of the mucosal diseases like oral ulcers, vaginal infections, sinusitis, and mucositis and dermatological diseases like wounds, inflammatory skin diseases, and systemic therapy through the transdermal route. The mechanical strength, drug loading and stabilization of HA and carrier polymers, chemical modifications and multifunctional nanocomposites have been enhanced, solving the inherent processing issues with HA electrospinning. However, toxicity of HA can change depending on the molecular weight, modifications and formulation ingredients. Clinical translation is still dependent on thorough toxicological evaluation and regulatory compliance. Translational barriers, such as mass-manufacturing, prolonged safety testing, regulatory issues, and clinical validation, still continue to pose a challenge despite promising preclinical results. This review summarizes the recent advancements in the field of HA nanofiber fabrication, physicochemical optimization, therapeutic use as well as translational perspective with particular focus on their future as the next-generation platforms to deliver drugs to the mucosal and skin.

Wound healing is a complex and coordinated biological process consisting of hemostasis, inflammation, proliferation and remodeling, which is regulated through the interaction of fibroblasts, immune cells, endothelial cells and extracellular matrix (ECM) components. Fibroblasts play a key role in mediating tissue repair, and they regulate collagen deposition, angiogenesis, cell migration, ECM remodeling, and wound contraction. However, the abnormal behaviour of fibroblasts in wounds causes non-healing and is not sufficiently addressed by conventional wound dressings. Sericin, a silk-based glycoprotein with many polar amino acids, is a promising biomaterial for regenerative wound healing owing to its biocompatibility, antioxidant, anti-inflammatory, moisturising and cell-adhesive properties. Recent studies demonstrated the positive effects of sericin-based materials on fibroblast survival, proliferation and migration, as well as modulation of oxidative stress and inflammatory responses. These effects are mediated through signalling pathways including TGF-β/Smad, PI3K/Akt and MAPK, all promoting matrix synthesis, angiogenesis and tissue remodeling. In this review, we critically discuss sericin-based composites and their fibroblast-targeted mechanisms in wound healing with respect to current advances, design strategies, translational challenges and future perspectives of next-generation regenerative biomaterials in general wound environments.

ABSTRACT Photodynamic therapy (PDT) is a minimally invasive cancer treatment that uses photosensitizers (PSs), light, and oxygen to generate cytotoxic reactive oxygen species. Natural product‐derived PSs, including alkaloids, flavonoids, polyphenols, curcuminoids, perylenequinones, phycocyanin, and anthraquinones, offer advantages such as biocompatibility and low toxicity but are limited by poor solubility, stability, and targeting. Nanotherapeutic systems such as organic, inorganic, and carbon‐based nanoparticles, nanogels, hydrogels, lipid carriers, and nanoemulsions address these limitations by enhancing stability, tumor accumulation, and controlled release. These platforms also enable multifunctional approaches, including imaging‐guided PDT, combination therapies, and stimuli‐responsive activation. This review highlights mechanisms, recent advances, and translational challenges of natural PS‐based nanotherapeutics across multiple cancers, emphasizing strategies to improve delivery, selectivity, and therapeutic outcomes for next‐generation PDT.