Current pharmaceutical design最新文献

Background: Apixaban (APX) prevents stroke and systemic embolism in patients with nonvalvular atrial fibrillation, as well as venous thromboembolism, and is marketed in tablet form.

Objective/method: This review provides an overview of analytical methods for evaluating APX in pharmaceutical matrices, with a focus on the eco-efficiency of green and white analytical chemicals. Studies published over the past decade were critically assessed to identify methodological trends and evaluate greenness using established assessment tools.

Results: The manuscript presents more than 40 analytical methods from the last 10 years for the evaluation of APX in pharmaceutical matrices. More than 75% of them are HPLC, and the majority, approximately 44%, use acetonitrile as a solvent. All methods presented were evaluated for their greenness profile. On average, they presented two green quadrants according to the National Environmental Methods Index (NEMI), a score greater than 75 on the Analytical Eco-Scale (ESA) in 88% of cases, an Analytical GREEnness Metric (AGREE) score of approximately 0.64, and all obtained more than 60 points on the Blue Analytical Grade Index (BAGI). Although eco-efficient options for APX evaluation in pharmaceutical matrices exist, the choice must be aligned with the intended objective, analysis routine, team training, time, resources, and cost.

Conclusion: Therefore, continuous refinement of practices is essential to ensure that methods remain efficient, robust, and environmentally responsible.

Introduction: This study employed network pharmacology and molecular docking to investigate the mechanism of Inula helenium in treating liver cancer.

Methods: Active compounds and their targets were identified from Inula helenium using HERB and Swiss Target Prediction. After standardizing target names via UniProt, liver cancer-related genes were collected from GeneCards and OMIM. Venny 2.1 analysis yielded 57 overlapping targets. A PPI network was constructed with STRING 11.5, and functional enrichment analyses were conducted using DAVID. GO analysis revealed multiple biological processes, cellular components, and molecular functions, while KEGG analysis highlighted key pathways including chemical carcinogenesis, IL-17, and NF-κB signaling. Thirteen core targets (e.g., TNF, IL1B, PTGS2, GSK3B, and MAPK14) were identified, and molecular docking confirmed their strong binding with active compounds.

Results: Inula helenium may treat liver cancer by modulating targets such as TNF, PTGS2, GSK3B, and MAPK14, as well as pathways like IL-17, NF-κB, and hepatitis B, thereby suppressing tumor growth and apoptosis.

Discussion: The findings support the anti-hepatocellular carcinoma effect of Inula helenium and suggest potential mechanisms, though further clinical validation is needed due to inherent limitations of network pharmacology.

Conclusion: This study offers a theoretical basis for the clinical use of Inula helenium in liver cancer treatment and encourages further investigation.

Introduction: This study elucidates molecular mechanisms underlying sanguinarine (SAN)- mediated inhibition of Lung Adenocarcinoma (LUAD) progression.

Methods: Potential targets for SAN and LUAD were obtained from public databases. A Protein-Protein Interaction (PPI) network was constructed, and core targets were visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with DAVID, while Reactome, WikiPathways, and MSigDB Hallmark analyses utilized Enrichr. Core targets expression and immune infiltration in LUAD were validated using The Cancer Genome Atlas (TCGA). Molecular docking assessed binding affinity between SAN and core targets, and in vitro experiments confirmed SAN's suppression of LUAD progression via the TGF-β1/Smad3 pathway.

Results: Ten core targets of SAN in LUAD were identified. GO analysis revealed biological processes including proliferation, apoptosis, and signal transduction. Significantly enriched cancer-related pathways included PI3K-Akt, MAPK, Ras, and TGF-β signaling, the latter of which was significantly enriched across KEGG, Reactome, WikiPathways, and MSigDB Hallmark analyses. Molecular docking demonstrated a strong binding affinity between SAN and core targets. In vitro, SAN suppressed proliferation and autophagy in A549 cells while promoting apoptosis by inhibiting the TGF-β1/Smad3 signaling pathway.

Discussion: The results demonstrate SAN's multi-target action against LUAD, notably through the inhibition of TGF-β1/Smad3, providing a mechanistic basis within oncogenic networks. Limitations include reliance on in vitro models and the preclinical focus. Future work requires in vivo validation and clinical translation.

Conclusion: This study identifies key targets and pathways for SAN's inhibition of LUAD progression, validating its effect through the suppression of TGF-β1/Smad3 and providing experimental evidence for clinical application in LUAD therapy.

Introduction: Myocarditis (MC) is an inflammatory cardiomyopathy with high morbidity and mortality. Current treatment options for MC have limitations and side effects, necessitating the exploration of new therapies. Traditional Chinese Medicine (TCM), particularly Huaiqihuang Granules (HQH), has shown promise due to its anti-inflammatory, antioxidative, and anti-apoptotic properties. However, the application in cardiovascular diseases remains underexplored.

Methods: We employed network pharmacology, molecular docking, and Molecular Dynamics (MD) simulations to evaluate HQH's effects on MC. This involved identifying bioactive components and therapeutic targets, conducting enrichment analyses, and performing molecular docking and MD simulations to validate the interactions between HQH components and MC-related targets.

Results: A total of 57 bioactive components in HQH and 143 potential therapeutic targets for MC were identified. Enrichment analyses revealed that HQH's potential treatment effects on MC involve various processes and pathways, including response to lipopolysaccharide, peptidase activity, the extracellular region, and pathways in cancer. Molecular docking indicates that Physalin A, sibiricoside A_qt, zhonghualiaoine 1, and methylprotodioscin_qt, along with ALB, PTGS2, AKT1, ESR1, and MMP9, may serve as key therapeutic components and targets. MD simulations confirmed strong interactions between HQH's core components and MC-related targets, supporting their potential therapeutic effects.

Discussion: This study suggests that HQH exerts therapeutic effects against MC through multi-target mechanisms and stable targets. These findings provide valuable insights into alternative treatment strategies for MC, offering a foundation for further research and clinical exploration.

Conclusion: This study confirms that HQH can influence MC through various active components and multiple therapeutic targets.

Background: Citrus reticulata (CR) has a long-standing role in traditional medicine, primarily due to its bioactive constituents such as hesperidin and narirutin, which are known for their antioxidant, antiinflammatory, antibacterial, and anticancer properties.

Objective: This study investigates the anti-proliferative activity of CR water extracts against DU-145 prostate cancer cells and explores the therapeutic potential and underlying molecular mechanisms of hesperidin and narirutin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) through network pharmacology and molecular docking approaches.

Methods: Cytotoxicity assays were employed to determine the anti-cancer efficacy (IC50) of processed CR water extracts in DU-145 cells. Targets related to hesperidin, narirutin, PCa, and BPH were identified using bioinformatics platforms. Network pharmacology was applied to construct compound-target interaction networks and perform enrichment analyses (GO, KEGG, and DisGeNET) to elucidate key signalling pathways. Molecular docking was conducted to validate compound-target interactions.

Results: Soil-processed CR extracts exhibited the strongest anti-cancer activity (IC50 = 1.789 mg/mL). Enrichment analyses identified significant pathways, including AGE-RAGE signalling, p53 signalling, inflammation, angiogenesis, and apoptosis. Molecular docking confirmed strong binding affinities of hesperidin and narirutin to the predicted targets.

Conclusion: Anti-proliferative assays, network pharmacology, and molecular docking collectively demonstrate that hesperidin and narirutin from CR show strong therapeutic potential against PCa and BPH. The findings highlight the involvement of AGE-RAGE and p53 signalling pathways and support the potential of these compounds in future drug development.

Iron deficiency (ID), with or without anemia, is a frequent and underrecognized condition among patients undergoing cardiac surgery, and it is associated with worse perioperative outcomes, including higher mortality, longer ICU and hospital stays, and increased transfusion requirements. This review summarizes current evidence on the prognostic role of ID and the effectiveness of supplementation strategies. While intravenous iron therapy has shown potential to improve hemoglobin levels and reduce transfusion needs, study results remain inconsistent, partly due to differences in timing, dosage, and formulations used. Newer oral agents and nanotechnology-based delivery systems offer improved bioavailability and tolerability, though clinical data in cardiac surgery remain limited. Overall, routine preoperative screening for ID using ferritin and Transferrin Saturation is essential, particularly in non-anemic patients, as timely supplementation may improve perioperative recovery. Intravenous administration remains the preferred method in moderate to severe cases. However, standardized protocols and further high-quality randomized trials are required to define the optimal management of iron deficiency in this high-risk population.

Background: Diabetic Nephropathy (DN) is a Chronic Kidney Disease (CKD), and its main pathological changes are renal tubular injury and glomerulosclerosis. Semen Ziziphi Spinosae (SZS) is the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow. As a triterpene saponin, Jujuboside A (Ju A) is the main active substance isolated from SZS. This study sought to investigate the potential effect and mechanism of Jujuboside A against DN.

Methods: The anti-apoptotic effects of Ju A on renal parenchymal cells of DN were examined by in vivo and in vitro studies. Molecular docking and Molecular Dynamics (MD) simulation revealed that Ju A could bind to TNF-α and Caspase-3 via forming stable receptor-ligand complexes, respectively. Immunofluorescence (IF) staining and ELISA detection were carried out to investigate the potential mechanisms by which Ju A exerted its amelioration effect on DN.

Results: Our study showed that, accompanied by the restored renal function, Ju A inhibited apoptosis of renal tubules and glomeruli in vivo and in vitro. Network pharmacology revealed that 42 overlapping targets were related to Ju A and DN. Among them, IL6, IL1B, TNF, VEGFA, EGFR, ALB, IGF1, FGF2, CASP3, and ESR1 were the top 10 targets. Ju A could bind to TNF-α and Caspase-3 via forming stable receptor-ligand complexes, respectively, as demonstrated by molecular docking and MD simulation. Ju A decreased the protein levels of TNF-α and IL-1β in renal tubules and glomeruli of diabetic mice, and in HG-cultured HK-2 cells and podocytes, leading to the alleviation of inflammation. Besides, the up-regulated relative phosphorylation levels of NF-κB p65 and cleaved caspase-3 were also down-regulated by Ju A in vivo and in vitro.

Discussion: The research showed that Ju A had a high affinity for Caspase-3 and TNF-α, and the underlying mechanism of Ju A against DN was the inhibition of apoptosis in renal tubular epithelial cells and podocytes. These findings strengthened the evidence that Ju A could be a potential treatment strategy for DN and offered opportunities for therapeutic advances in the field.

Conclusion: Ju A could inhibit apoptosis and alleviate inflammation of renal parenchymal cells by inactivating the TNF-α/NF-κB p65/Caspase-3 signaling pathway, exerting renal protective effect against DN.

Peritoneal dialysis (PD) is one of the commonly used treatments for patients with end-stage renal disease (ESRD). Despite technological advances, mortality rates in patients with PD remain high. Nutritional status is an important factor affecting the prognosis of PD patients; low protein, as a complication of PD patients after dialysis, may lead to malnutrition, oedema of both lower limbs or whole body, decreased immunity, aggravation of the condition and other adverse consequences. It will also increase the mortality rate of patients and increase the incidence of cardiovascular and cerebrovascular diseases, which is considered to be the main limiting factor of PD. As a substitute for traditional glucose dialysate, Amino Acid Deritoneal Dialysate (AAD) stimulates protein synthesis by increasing amino acid availability in PD patients and inducing hyperamino acidemia due to its sugar-free and good biocompatibility. Based on literature retrieved from PubMed, Web of Science and Scopus, we found that AAD can not only effectively improve the nutritional status of PD patients, but also effectively alleviate the complications of low protein caused by traditional dialysate. Although AAD has shown promise in the treatment of low-protein patients, further randomized controlled trials are needed to verify its long-term efficacy and safety. AAD provides a new treatment option for patients with low protein, which has vital clinical significance.

Citrus fruits are an abundant source of the polyphenolic phytoconstituent naringenin, which belongs to the class of flavanones. NRG shows a lot of potential as a drug for treating a number of CNS disorders, such as neuroprotective activity, antiamyloidosis, antiparkinson, antialzheimer activity, and more. However, naringenin's hydrophobic nature, which results in limited absorption, limits its therapeutic potential. In this article, we provide an outline of the variety of nanocarriers employed for delivering naringenin as carriers. Some of them include solid lipid nanoparticles, liposomes, micelles, polymeric nanoparticles, nanostructured lipid carriers, nanosuspensions, and nanoemulsions, among others. These formulations of naringenin nanomedicine have been used for the potential treatment of a series of CNS disorders. Based on various research reports, it can be said that with the right nanocarriers, naringenin proves to be a promising therapeutic alternative for the treatment of several CNS ailments, including neurological diseases, Alzheimer's, Parkinson's disease, cerebral ischemia, etc. Therefore, the present manuscript highlights the various aspects of naringenin and its pharmacological activities. Further, naringenin-loaded nanocarriers have been enlisted and discussed in detail.

Interventions to reduce smoking prevalence aim to help patients quit smoking to cut down its hazards and related impairments in human beings. Pharmacological treatments are recommended for those with high levels of addiction because of severe physical and psychological dependence. Use of pharmacotherapy can double the odds of successful quitting. Nicotine replacement therapy (NRT), drug treatment regimens including nicotinic receptor agonists (varenicline), dopamine and norepinephrine reuptake inhibitors (bupropion), cytisinicline (cytisine), and combination therapy (NRT + medication) can be employed on a case-by-case basis. Furthermore, varenicline has been found to be more effective than the other agents in most studies. The most common adverse effects of pharmacological agents include depression, nausea, anxiety, abnormal dreams, and insomnia. On the other hand, electronic cigarettes offer another alternative to aid in smoking cessation (SC). Endurance of SC is mostly related to the employment of combined approaches, such as counselling and pharmacotherapy. This study is designed to provide an up-to-date overview of the contemporary approach to interventions aimed at helping patients in SC.