Future Journal of Pharmaceutical Sciences最新文献

Background

Sepia pharaonis, a marine cuttlefish, contains bioactive compounds such as posterior salivary gland toxin with medicinal potential, though its pharmacological effects are largely unknown. This research is one of the first comprehensive studies to explore the chemical composition, antioxidant capacity, and anticancer effects of sepia ink against chemically induced HCC in rats, integrating in-vitro, in-vivo, and in-silico approaches. These findings suggest Sepia ink polysaccharides (SIP) could provide a low-toxicity, multi-targeted therapeutic option for HCC, potentially overcoming limitations of current standard treatments like drug resistance and organ toxicity. This study investigates Sepia ink's chemical composition, antioxidant properties, and anticancer potential. Hepatocellular carcinoma (HCC) was induced in rats using N-nitrosodiethylamine (DEN) and phenobarbitone (PB). SIP were administered intraperitoneally at high doses (400 mg/kg), and its effects on body weight, liver marker enzymes, antioxidants (enzymatic and non-enzymatic), phase I metabolizing enzymes, and macromolecular damage in the liver were evaluated.

Results

In-vitro studies on HepG2 cells demonstrated an IC₅₀ > 80 μM. Histopathological and biochemical analyses confirmed SIP’s dose-dependent hepatoprotective activity, restoring altered parameters to near-normal levels. High-performance thin layer chromatography (HPTLC) revealed seven bioactive compounds in SIP. In-silico studies identified Fucoidan Ligand-7 as a potent inhibitor of the Bcl-2 receptor, with a binding energy of −14.54 kcal/mol. Western blot analysis showed significant reductions in tumor necrosis factor-alpha (TNF-α) level in SIP-treated HCC rats. Alpha-fetoprotein (AFP), a liver tumor biomarker, was significantly reduced in the SIP-treated group compared to the DEN-induced group.

Discussion

These findings highlight SIP’s hepatoprotective and anticancer potential, suggesting its therapeutic value against DEN-induced HCC and its ability to enhance the antioxidant defense system.

Graphical Abstract

Background

Statins are widely prescribed for their lipid-lowering effects, yet their association with mitochondrial dysfunction remains a significant clinical concern. Although the mechanisms underlying statin-induced mitochondrial effects have been extensively studied, the role of monocarboxylate transporters (MCTs) in this process has not been directly examined. While direct evidence is limited, emerging data suggests a plausible intersection. We propose a novel hypothesis that statin-mediated modulation of MCT activity may alter lactate transport and mitochondrial energetics via non-classical pathways, offering a new perspective on the pathophysiology of statin-related myopathy (SRM).

Main body

This review synthesizes current evidence on how statins may interfere with lactate transport, potentially impacting the regulation of mitochondrial genes or pathways across cellular environments including, but not limited to, skeletal muscle. Drawing from both in vitro and in vivo studies, two key observations emerge: (i) statins are capable of impairing mitochondrial function, and (ii) MCTs are essential for maintaining mitochondrial function by regulating the flux of lactate and other monocarboxylates. Emerging research indicates that impaired lactate transport, particularly through inhibition of MCT1 and MCT4, may contribute to mitochondrial dysfunction in muscle tissues. This disturbance compromises the activity of mitochondrial complex I and III, triggering a cascade of metabolic consequences: impaired oxidative metabolism, reduced ATP production and elevated production of reactive oxygen species. Furthermore, SRM have been linked to diminished mitochondrial DNA (mtDNA) content and dysregulation of key genes governing mitochondrial homeostasis and biogenesis (such as mtDNA, PGC-1α, SOD1, SOD2), dynamics (MFN2, FIS1) and oxidative phosphorylation (CPT2, Complex I-IV). Notably, modulating MCT function has emerged as a promising strategy for repurposing statins as anticancer agents. Dysregulation of MCT activity by statins has been implicated in cancer cell survival, proliferation, and metabolic reprogramming.

Conclusion

Clarifying MCT involvement in statin-induced mitochondrial dysfunction has expanded our perspective into both adverse effects and anti-cancer potential of statins, inspiring new strategies in translational cardiovascular medicine and oncology research. This conceptual framework highlights the need for integrative studies bridging MCT biology with mitochondrial pharmacotoxicology.

Background

Diabetes mellitus is the main root of mortality worldwide and a major cause of death by 2030. As the global medical landscape shifts, diabetes presents a serious challenge to standard treatment methods. Orally administered insulin, used for treatment, has drawbacks including instability in the gastrointestinal system due to degrading enzymes and low absorption, resulting in comparatively poor uptake. Nanotechnology introduces remarkable possibilities for diabetes treatment through targeted and accurate drug delivery. Among various nanodosage forms, nanosponges and nanocrystals are considered the most appropriate strategy for diabetes care. The study intends to enhance the bioavailability of voglibose by encapsulating it in a voglibose nanosponges formulation (V-NSF) and a voglibose nanocrystals formulation (V-NCF). Design of experimentation was successfully carried out using the Box–Behnken design. The response parameters, essentially particle size, entrapment efficiency and PDI, have been speculated, followed by observed values using a particle size analyzer and entrapment efficiency methods. Various characterization parameters, such as in vitro drug release, FTIR, thermal analysis (DSC and XRD) and surface morphology (SEM), were used to analyze the results, accompanied by stability studies of the optimized formulation and in vivo studies performed using Sprague–Dawley rats.

Results

The particle size of V-NSF was 270.63 ± 5.9 nm, and the PDI value was 0.165 ± 0.027. Entrapment efficiency was 78 ± 0.32%. In case of V-NCF, particle size was analyzed as 131 ± 0.31 nm, PDI value of NCF was 0.140 ± 0.006, and entrapment efficiency was 74 ± 0.28%. All physical and chemical characterization parameters were confirmed by FTIR, SEM, DSC, XRD and in vitro release.

Conclusion

V-NSF and V-NCF exhibited confined size distribution, acceptable polydispersity index and greater value of entrapment efficiency. The pharmacodynamic studies showed that V-NSF elicits a remarkable antidiabetic effect compared to V-NCF, with moderate efficacy than voglibose itself. The data of optimized formulations can be useful for clinical implications and suggest that V-NSF and V-NCF could be effective in diabetic management.

Graphical abstract

Background

Alzheimer’s disease (AD) presents a significant challenge in healthcare due to its progressive neurodegenerative nature. Current treatments are limited, prompting the search for novel therapeutic strategies. Phytochemicals from medicinal plants offer potential neuroprotective effects, targeting various pathways implicated in AD pathogenesis. Moringa oleifera, known for its diverse health benefits, presents a promising source of phytochemicals with therapeutic potential against AD. This study aimed to investigate the neuroprotective properties of M. oleifera phytochemicals, particularly their interactions with cathepsin B, a novel target in AD pathology.

Results

Phytochemical analysis of M. oleifera seed extract revealed the presence of bioactive compounds, including catechin, naringenin, and ellagic acid, among others. Molecular docking simulations identified moringyne and ellagic acid as top candidates for interacting with cathepsin B, showing favorable binding affinities compared to a standard drug (Z-FA.FMK). Furthermore, ADMET prediction indicated favorable pharmacokinetic properties for moringyne and ellagic acid, suggesting their suitability as oral drugs. Molecular dynamics simulations confirmed stable interactions between the identified compounds and cathepsin B over 250 ns, with ellagic acid exhibiting superior stability. MM/GBSA analysis ranked ellagic acid as the most potent inhibitor of cathepsin B, supporting its potential therapeutic efficacy.

Conclusion

This study demonstrates the potential of M. oleifera phytochemicals, particularly moringyne and ellagic acid, as novel therapeutic agents against AD through their interaction with cathepsin B. These findings further demonstrate the importance of natural compounds in drug discovery and development for neurodegenerative diseases. Further preclinical and clinical studies are warranted to validate the efficacy and safety of moringyne and ellagic acid in AD treatment.

Background

As of 2025, the World Health Organization (WHO) reports that cancer remains a leading cause of death globally. The global Healthy Life Expectancy (HALE) at birth was estimated at 63.5 years in 2019, reflecting the average number of years a person can expect to live in full health. Chronic diseases like cancer significantly impact HALE, underscoring the need for effective interventions. The epidermal growth factor receptor (EGFR) is a validated therapeutic target, especially in cancers with EGFR overexpression or mutations. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved clinical outcomes; however, resistance and limited efficacy in some patients demand the development of novel inhibitors. Heterocyclic scaffolds, such as thiazole and pyrazole, have garnered attention for their broad-spectrum anticancer properties, including EGFR inhibition. The synthesis of hybrid molecules combining thiazole and pyrazole cores has further enriched the scope of potential EGFR-targeted anticancer agents.

MainText

This review presents an in-depth analysis of thiazole, pyrazole, and their hybrid derivatives as promising EGFR-TKIs. We have summarized literature from 2008–2025, highlighting structure–activity relationship (SAR) trends, biochemical assay outcomes, and computational insights. The most potent compounds demonstrated submicromolar IC₅₀ values against EGFR and robust cytotoxicity in various cell lines. Conversely, least potent analogs often lacked these structural features or bore bulky or electron-donating groups at critical positions. Biochemical assays confirmed selective EGFR inhibition, while molecular docking and dynamics studies supported the favorable binding profiles of active compounds within the ATP-binding pocket of EGFR.

Conclusion

Thiazole, pyrazole, and their hybrids represent a promising class of EGFR-targeted anticancer agents. A combination of rational SAR-based modifications, supportive biochemical assay results, and computational modeling has laid the foundation for their further optimization. Continued efforts in hybrid design, guided by structural insights, may lead to the development of next-generation EGFR-TKIs capable of overcoming current therapeutic limitations.

Graphic abstract

Background

The present study aims to improve safety and quality assurance of swimming pools located in Sharkia governorate, Egypt. A total of 144 water samples were collected from eight pools. The water quality of the tested pools was assessed according to national swimming pool quality standards in terms of physiochemical and microbial characterization. Microbial contamination was assessed by the detection and enumeration of standard indicator organisms. 16S rDNA sequencing and phylogenetic analysis were utilized for further identification of most resistant bacterial isolate. Antimicrobial susceptibility to various natural potentially antimicrobial agents; including aqueous, alcoholic plant extracts and essential oils was conducted. Both MIC and MBC for tested natural antimicrobial agents were determined. Finally, field application of the most effective antimicrobial agents was carried out to highlight the cons and pros of their usage in field, in order to possess a broader scope of both theoretical and practical aspects of this study.

Results

In terms of physical analysis; 82.9% of tested samples were nonconformed to temperature standard, while 100% were conformed to color and odor. Regarding chemical analysis; 54.3% and 53.3% of samples were nonconformed to alkalinity and combined chlorine, respectively. Assessment of microbial contamination indicated the prevalence of Pseudomonas aeruginosa as a main contaminator of tested pool water (57.1%) followed by total coliforms which ranked second among detected microorganisms (52.4%). Upon performing antimicrobial susceptibility testing of plant extracts and essential oils, cinnamon hot water extract and essential oil showed narrowest MIC ranges. Upon testing various combinations between different tested antimicrobial agents, combination of cinnamon hot water extract and clove essential oil was identified as a promising synergetic combination against resistant isolates. In field application of the most effective antimicrobial compounds resulted in that compatibility markedly decreased for physical standards and slightly for chemical standards. However, microbial pollution was totally eliminated after treatment, which was considered and discussed within the context of the study.

Conclusion

This study targeted full assessment of pools water in Egypt, one of the most prominent findings of this study is prevalence of P. aeruginosa as the main resistant microorganism responsible for microbial pollution of pool water. Cinnamon hot water extract and clove essential oil were identified as the most effective natural antimicrobial agents used in the study. Field application of these antimicrobial agents was a significant step confirming the validity and credibility of current results highlighting the pros and cons of practical application of the suggested pool decontaminators.

Acute lymphoblastic leukaemia (ALL) is a crippling childhood cancer where usually a rare white blood cell runs amok, multiplying uncontrollably. Pegasparaginase, a vital weapon in the ALL arsenal, starves leukaemic cells by depleting asparagine, their lifeline. However, current treatments are plagued by issues like debilitating hypersensitivity, fleeting enzyme stability, and inadequate delivery methods. This review explores groundbreaking solution, the immobilization of pegasparaginase using fungal chitosan for direct intravenous administration. Cutting-edge computational modeling to optimize the enzyme–nanoparticle interaction ensures potent and long-lasting activity. IoT and IoMT integration with smart sensor would enable improved efficiency, decision making, and remote monitoring, while AI and ML can be utilized for drug discovery processes, optimizing drug design for therapeutic applications and forming nanomedicine-based treatment outcomes, respectively. Key parameters like enzyme loading, cross-linking density, and nanoparticle size were meticulously adjusted for peak therapeutic performance. The encapsulation process shields pegasparaginase from the harsh realities of the body, enabling controlled release and sustained enzyme activity. This transformed enzyme boasts improved pharmacokinetics, a longer lifespan and reduced hypersensitivity reactions overcoming the crippling limitations of existing therapies. This approach is particularly aligned with the needs of paediatric ALL patients, who are the majority and highly susceptible to side effects of treatment. Chitosan-based fungal nanoparticles offer a superior, controlled, and biocompatible delivery system, maximizing therapeutic potential of pegasparaginase, while minimizing immunogenic risks. To sum up, this study presents a novel and potent strategy for pegasparaginase immobilization, combining computational brilliance with experimental innovation to conquer the most pressing challenges in ALL treatment. These findings strongly suggest the potential of delivery systems to curb adverse reactions and amplify enzyme efficacy, making them a prime candidate for clinical applications. Future research should focus on scaling up production and conducting clinical trials to validate these findings and explore broader applications for enzyme-based therapies in other diseases. This review underscores the immense potential of integrating nanotechnology and permissible biocompatible materials to revolutionize therapeutic approaches in oncology.

Graphical Abstract

Background

The major focus of the research was to optimize and validate an eco-friendly, cost-effective, high-performance and throughput RP-HPLC technique for the quantification of Cinnarizine in marketed formulation and also evaluate intrinsic stability. Further, the proposed analytical method efficiency was compared with three reported methods using green and white algorithmic matrix viz., AES, AGREE, GAPI, RGB and BAGI.

Results

Chromatographic conditions were optimized with Inertsil ODS-3V column (250 × 4.6 mm, 5 μm) with methanol and 0.1% v/v orthophosphoric acid (pH 2.5) in a 95:05 v/v ratio as mobile phase. The analytical wavelength and flow rate were fixed to 254 nm and 0.5 mL min⁻¹, respectively. Inherent stability profile was also carried out as per ICH Q₁A R₂ guidelines. The Cinnarizine was eluted from the column at 3.328 min and the method was validated in accordance with ICH Q₂ R₁. The optimum linearity of the analytical method was fitting over the range of 2–14 µg mL⁻¹ with a correlation constant of 0.9992. The limits of detection and quantification were 0.00621 µg mL⁻¹ and 0.0207 µg mL⁻¹, respectively. The Cinnarizine was found to be stable in acidic, thermal and photolytic conditions. Whereas, maximum degradation has taken place in basic and oxidative degradation. The Greenness and whiteness of the optimized chromatographic conditions were better than those reported methods.

Conclusion

Overall, the optimized RP-HPLC method can be utilized for the quantification of Cinnarizine in the tablet formulation and to generate the stability profile.

Background

Understanding how a disease develops and the factors that influence any deviation from the balance created by the body is critical in tailoring appropriate treatment for each patient. Existing literature discusses each factor separately, and simply touches on the interaction by recognizing its existence. The objective of this study is to delve in to the relationship between the immune system and the gut microbiota, and how they in turn affect each other and ultimately lead to a diseased state.

Methods

To locate relevant published research, a comprehensive search of electronic databases was performed. Eligible studies were chosen based on predetermined inclusion criteria, which included original research publications exploring the link between the immune system and gut microbiome in IBD patients. Data extraction and quality evaluation followed the PRISMA recommendations. The included studies used a variety of techniques, including observational cohort studies, case–control studies, and experimental research.

Results

Changes in systems from homeostatic function include a dysregulated immune response with heightened pro-inflammatory cytokines, disrupted gut barrier permeability due to increased epithelial permeability and disrupted tight junctions, reduced microbial diversity with elevated levels of pathogenic strains and bacteriophages. Short-chain fatty acids which promote gut barrier integrity and possess anti-inflammatory effects are reduced in patients with IBD.

Discussion

Key findings from the literature review emphasize the role of gut microbiota in immunological responses in IBD, as well as the reciprocal impact of immune dysregulation on microbiome composition. Further research is needed to understand the molecular interaction between the immune system and the gut microbiota (Caron et al. in J Crohns Colitis 18:ii3–ii15, 2024. https://doi.org/10.1093/ECCO-JCC/JJAE082).

The aryl hydrocarbon receptor (AHR) ligand, 6-formylindolo[3,2-b]carbazole (FICZ), plays a pivotal role in modulating various biological processes, including circadian rhythms and maintenance of cellular homeostasis. This study aimed to investigate the pharmacokinetics, tissue distribution, and metabolic clearance of FICZ in vivo using high-performance liquid chromatography (HPLC) with fluorescence detection and an ethoxyresorufin-O-deethylase (EROD) assay. FICZ was administered intraperitoneally to rats in varying doses (42.6 µg/kg, 85.2 µg/kg, 127.9 µg/kg, and 426.4 µg/kg) at multiple time points (1, 3, and 6 h). The liver was identified as the primary organ for FICZ distribution, with peak concentrations observed at 1 h, whereas metabolism by cytochrome P450 enzymes, particularly CYP1A1, led to a significant reduction in FICZ levels over time. Additionally, heart, testis, and brain tissues exhibited varying FICZ accumulation patterns, with dose-dependent distribution observed in testes. The findings highlight the tissue-specific pharmacokinetics of FICZ, with its distribution influenced by both dose and exposure time. EROD activity, a marker for CYP1A1 induction, peaked at 3-h post-administration and was inversely correlated with FICZ degradation. The rapid metabolism of FICZ, exacerbated by its susceptibility to photodegradation, complicates the detection and quantification of endogenous FICZ in vivo. This study presents the first comprehensive assessment of FICZ pharmacokinetics and tissue distribution in various rat tissues, including the liver, heart, brain, prostate, and testis, while also exploring its link to CYP1A1 modulation. This study underscores the complexity of FICZ’s pharmacokinetic, suggesting that both dose- and tissue-specific responses play crucial roles in AHR activation and subsequent enzyme activity. These results contribute to a deeper understanding of FICZ’s biological effects, offering insights into its therapeutic potential and toxicological implication.