Future Journal of Pharmaceutical Sciences最新文献

Background

Diabetes mellitus is a multifactorial metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or action. Oxidative stress, impaired insulin signaling, and dysregulated glucose transport are central to its pathogenesis. Given the limitations and side effects of current pharmacotherapies, attention has shifted toward natural compounds with multitargeted mechanisms of action.

Purpose of the study

This study aimed to explore the antidiabetic potential of Chamazulene (Cham) and Cinnamic Acid (CA), natural bioactive compounds, through in silico and in vivo approaches, targeting key molecular pathways including IRS2/GLUT4, HNF4α, and GLUT2, as well as assessing their effects on oxidative stress, DNA integrity, and lipid metabolism.

Methods and results

Male Wistar rats were assigned into eight groups: three control groups (C, C+Cham, C+CA) and five streptozotocin-induced diabetic groups (DM, DM + Cham, DM+CA, DM+Cham + CA, and DM+Gli. Our study highlighted the inhibitory α-amylase effect of both nutraceuticals. Biochemically, DM+Cham+CA surpassed the single treatments effects on lowering blood glucose, improving lipid profile, balancing redox system evidenced by improving GPx and GR activity. Moreover, using flow cytometry and Comet test, the used treatments extended their beneficial effects to inhibit reactive oxygen species and DNA damage, respectively. Using qRT-PCR, the treated groups upregulated skeletal muscle IRS2, GLUT4 gene expression, downregulated hepatic GLUT2 and HNF4α. Notably, natural compounds outperformed the standard drug in several parameters.

Conclusion

The findings support the therapeutic promise of Chamazulene and Cinnamic Acid as natural alternatives or adjuncts to conventional antidiabetic drugs. Further studies involving diverse models and clinical validation are warranted to confirm efficacy and safety in humans.

Background

Cancer remains a major global health burden, contributing significantly to illness and death worldwide. Although current treatments such as chemotherapy, radiation therapy, and surgery have improved patient outcomes, they are frequently limited by severe side effects, drug resistance, and damage to healthy tissues. These challenges have prompted the search for novel, safer, and more targeted therapeutic options.

Main body

Rhamnetin, a naturally occurring compound found in various plants, has emerged as a promising candidate in cancer therapy due to its diverse range of biological activities. It has demonstrated the ability to induce programmed cell death in cancer cells, inhibit the formation of new blood vessels that support tumor growth, and prevent the transition of cancer cells to more invasive forms. Rhamnetin also regulates oxidative stress and mitochondrial function, contributing to its anticancer effects. Notably, it appears to preferentially affect cancerous cells while minimizing harm to normal tissues, suggesting a more targeted therapeutic profile. In addition to its individual therapeutic properties, rhamnetin has shown potential in enhancing the effectiveness of conventional treatments. By sensitizing cancer cells to existing therapies, it may help overcome resistance and improve overall treatment outcomes. Despite these promising effects, its clinical application remains limited by poor absorption, rapid metabolism, and low bioavailability. Recent advancements in drug delivery systems, including the use of nanoparticles and liposomes, offer promising strategies to address these limitations. These technologies have the potential to improve the stability, absorption, and targeting of rhamnetin, thereby enhancing its therapeutic value.

Conclusion

Rhamnetin represents a compelling natural compound with significant anticancer potential. Its ability to selectively target cancer cells, modulate multiple cancer-related pathways, and improve the efficacy of conventional treatments positions it as a valuable candidate for future cancer therapies. Continued research into optimized delivery methods and clinical applications is essential to fully harness its benefits in cancer treatment.

Background

Hypoxia has been recognized as a major contributor to cancer progression. Targeting hypoxia-derived factors, particularly in breast cancer, may present an auspicious strategy for cancer therapy. Honey-derived natural products have demonstrated therapeutic potential for various ailments, including cancer. However, research on their effects under hypoxic conditions remains limited. This study aims to elucidate the potential of honey-derived natural products as anticancer agents for breast cancer under hypoxic conditions. An integrative bioinformatics approach was employed, including drug-likeness screening, toxicity analysis, differential gene expression analysis, gene and protein enrichment analysis, immune infiltration correlation analysis, molecular docking, and molecular dynamic simulations.

Results

Five potential compounds with favorable drug-like properties and minimal toxicity effects were identified, including 2,2-dimethyl-8-prenylchromene, chrysin, galangin, kaempferol, and pinobanksin. These compounds were further assessed for their ability to target hypoxia-associated factors. Public database analysis revealed that N-myc downregulated gene-1 (NDRG1) is significantly upregulated in breast cancer under hypoxic conditions. Enrichment analysis demonstrated that elevated NDRG1 expression is strongly associated with poor patient outcomes. Interestingly, high NDRG1 expression is correlated with immune cell infiltration, including monocytes, myeloid-derived suppressor cells, and neutrophils, which are known components of the tumor microenvironment that promote cancer progression. Molecular docking results indicated that chrysin exhibited a more favorable binding affinity than other compounds, including the control drug Combretastatin A-4. Moreover, a 100-ns molecular dynamics simulation demonstrated that chrysin exhibited dynamic behavior comparable to the control drug across nearly all measured parameters, suggesting its potential as an anticancer agent.

Conclusion

These findings highlight the promise of chrysin as a candidate for breast cancer treatment under hypoxic conditions by targeting NDRG1. Further experimental validation is warranted to support its development as a therapeutic agent.

Background

Acute kidney injury (AKI) and chronic kidney disease (CKD) pose significant global health challenges, often worsened by the use of certain therapeutic agents and exposure to environmental toxins. This review aims to explore the nephroprotective role of botanicals, specifically focusing on the damage to kidneys caused by prolonged use of modern medicines and environmental toxicants.

Main body of the abstract

This review provides a detailed overview of Traditional Indian Medicinal Plants (TIMP), highlighting their botanical components and the potential mechanisms through which they offer nephroprotection in cases of chronic kidney disease. The analysis includes existing research studies on the nephroprotective effects of these plants, particularly in the context of both acute and chronic kidney diseases. Findings suggest that botanicals derived from TIMP hold promising potential for developing nephroprotective therapies.

Short conclusion

Research has shown that TIMP can effectively reduce kidney damage induced by various nephrotoxic agents, as evidenced by studies on animal models. Some of the TIMP with notable potential for treating chronic kidney disease include Camelia sinensis (L.), Nigella sativa (L.), Andrographis paniculata (Burm.f.), Daucus carota (L.), Foeniculum vulgare (L.), Glycyrrhiza glabra (L.), and Cucumis sativus (L.).

Graphical abstract

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.