Pharmaceuticals最新文献

{"title":"Potential Ameliorative Effect of Aged Liubao Tea Aqueous Extract on D-Galactose-Induced Pathological Damage in an Alzheimer’s Disease Zebrafish Model","authors":"Shini Zhang, Xiao-Li Luo, Hangxing Yang, Ganghua Huang, Jing Leng, Tao Yang","doi":"10.3390/ph19091336","DOIUrl":"https://doi.org/10.3390/ph19091336","url":null,"abstract":"Background: Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder for which effective treatments remain limited. Liubao tea, a distinctive post-fermented dark tea, develops unique aged and areca nut aromas through prolonged storage. However, comprehensive studies on its anti-Alzheimer’s disease effects are lacking. This study aimed to identify the bioactive constituents of Liubao tea with varying storage durations and aroma profiles, and to further evaluate its neuroprotective potential against Alzheimer’s disease. Methods: Chromatography and spectrophotometry were employed to quantitatively determine the primary bioactive components in various Liubao tea samples. A D-galactose-induced Alzheimer’s disease zebrafish (Danio rerio) model was established to evaluate the neuroprotective effects of the aqueous extract of Liubao tea. Results: The contents of theabrownins, theaflavins, tea pigments, and catechins showed potential associations with the anti-AD capacity of Liubao tea. Variations in these bioactive components appeared to correlate with the neuroprotective activity. Conclusions: This study elucidates the anti-AD potential of aged Liubao tea and associates its characteristic constituents with neuroprotective effects. The findings provide essential theoretical support for developing Liubao tea as a promising natural product candidate worthy of further anti-AD research.","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 9","pages":"1336-1336"},"PeriodicalIF":0.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148861331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational Design of Novel Thiazole-Clubbed Pyrimidine-Linked Hydrazone Conjugates as Promising RSK4 Inhibitors for Esophageal Squamous Cell Carcinoma: Molecular Dynamics Simulations and In Vitro Evaluation.","authors":"Mujeeb Ul Naeem, Syeda Farwa Naqvi, Yousaf Khan, Samina Aslam, Syed Aminullah, Azmatullah Khan, Thoraya A Farghaly, Wajid Rehman","doi":"10.3390/ph19081323","DOIUrl":"10.3390/ph19081323","url":null,"abstract":"<p><p><b>Background:</b> Esophageal squamous cell carcinoma (ESCC) remains highly aggressive and continues to limit clinical treatment for substantial cancer-associated morbidity and mortality worldwide. Despite advances in therapeutic interventions the lack of effective molecularly targeted treatments continues to restrict clinical management beyond conventional chemotherapy and radiotherapy. Among these therapeutic targets the ribosomal S6 kinase 4 (RSK4) has gained considerable attention because of its critical involvement in ESCC progression, survival and proliferation, suggesting its potential as a potential target for anticancer drug development. <b>Methods:</b> A series of thiazole-clubbed pyrimidine linked hydrazone hybrids (<b>1</b>-<b>14</b>) were synthesized via 4-aminothiazole-5-carbohydrazide functionalized intermediates and fully characterized and evaluated for their inhibitory activity against RSK4. <b>Results:</b> Biological assessment demonstrated that the synthesized analogues exhibited remarkable potency, with IC₅₀ values between 15.32 ± 1.35 and 54.61 ± 2.17 nM compared with the reference inhibitor BI-D1870 (IC₅₀ = 33.16 ± 1.34 nM). Among the evaluated compounds, <b>2</b>, <b>8</b>, <b>9</b>, <b>13</b> and <b>14</b> emerged as the most potent candidates and showed pronounced activity towards RSK4. For further insights into the molecular basis of their activity the lead candidates were subjected to computational investigations, such as molecular docking, molecular dynamics simulations, in silico ADMET and ProTox-3.0 characterization. The computational analyses provided structural and pharmacological insights into experimentally observed RSK4 inhibitory activity, like predicted interactions, stability dynamically and preliminary ADMET/toxicity characteristics. This study supports the need for further optimization and experimental validation of the identified RSK4 active lead candidates. <b>Conclusions:</b> These findings highlight the thiazole-clubbed pyrimidine-linked hydrazone scaffold as a potential chemotype for promising scaffolds targeting RSK4 lead discovery, and the identified candidates warrant further investigation into ESCC cellular models to establish anticancer efficacy and pathway-level activity.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeepBBB: A Data-Composition-Aware Graph Screening Workflow for BBB-Focused CNS Library Construction and Prospective PAMPA-BBB Evaluation.","authors":"Ziying Xu, Wei Xia, Haiqiang Wu, Haiping Zhang","doi":"10.3390/ph19081319","DOIUrl":"10.3390/ph19081319","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Blood-brain barrier (BBB) permeability is a major practical obstacle in central nervous system (CNS) drug discovery, because only a small fraction of drug-like molecules achieve sufficient brain exposure. <b>Methods:</b> We present DeepBBB, a graph-based, data-composition-aware screening workflow for predicting BBB permeability and for constructing BBB-focused screening libraries from commercial chemical space. Rather than introducing a new graph-learning architecture, the workflow combines standard graph convolutional and graph-transformer models with deliberate control of training-set composition, commercial-library filtering, chemical-space profiling, and prospective experimental evaluation. Three model variants were trained on the Blood-Brain Barrier Database (B3DB): a baseline classifier/regressor pair (DeepBBB_V1_BC/RG), a variant trained with a more strongly negative-enriched configuration (DeepBBB_V2_BC), and a graph-transformer counterpart (DeepBBB_trans_BC/RG). Because the sample-level split assignments and per-compound predictions from the original runs were not recoverable, the archived summary metrics are reported descriptively in the main text and are not used to support calibration, scaffold-level validity, or generalization. Applying the workflow to the ChemDiv collection (~1.5 million compounds) and the Enamine REAL lead-like space (~1.7 billion compounds) produced three progressively more stringently filtered BBB-focused libraries (21,991; 4,808,885; and 151,790 compounds). <b>Results:</b> Analysis of available processed data indicated that the predicted BBB-permeable set occupies a compact, BBB-compatible property region. Physicochemical, fragment, and scaffold summaries were interpreted descriptively at the constructed-library level. In a first prospective campaign, one of 12 tested candidate compounds was PAMPA-BBB-positive (all-tested molecular-level positive fraction 8.3%; exact 95% CI 0.2-38.5%). In a second campaign, five of 35 tested candidate compounds were PAMPA-BBB-positive (14.3%; exact 95% CI 4.8-30.3%); 13 compounds were not quantifiable and were not treated as ordinary CNS-negative measurements, and the two campaigns differed in compound source, selection strategy, and assay setting, so the numerical difference is reported descriptively rather than causally. <b>Conclusions:</b> Together, these results support the feasibility of BBB-focused computational filtering and a PAMPA-BBB evaluation workflow for CNS-oriented discovery.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Computational Workflow for Discovering Alkaloid-Derived Ligands of Cyclin-Dependent Kinase 2.","authors":"Anh Tuan Do, Quoc Long Pham, Huong Thi Thu Phung, Minh Quan Pham","doi":"10.3390/ph19081320","DOIUrl":"10.3390/ph19081320","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cyclin-dependent kinase 2 (CDK2) is a key regulator of cell-cycle progression and a potential anticancer target. This study aimed to identify alkaloid-derived CDK2 ligands using an integrated computational workflow and to obtain preliminary evidence of their effects on cancer-cell viability. <b>Methods:</b> Molecular docking with mVina and fast pulling of ligand (FPL) simulations were benchmarked using 20 experimentally characterized CDK2 inhibitors. A library of 2692 PubChem-derived alkaloids was screened, followed by ADMET evaluation, 100 ns molecular dynamics simulations, and FPL-based relative-affinity re-ranking. The three prioritized compounds were evaluated in HepG2 and HGC-27 cells using an MTT assay after 48 h of exposure. <b>Results:</b> Docking and FPL showed correlations with experimental affinity data of R_Dock = 0.549 ± 0.180 and R_W = -0.676 ± 0.119, respectively. <b>CID 636885</b>, <b>CID 46184320</b>, <b>and CID 101691758</b> were prioritized for detailed evaluation. All three compounds reduced cell viability, with lower IC₅₀ values observed in HepG2 cells than in HGC-27 cells. <b>CID 101691758</b> exhibited the highest growth-inhibitory activity among the tested compounds, with IC₅₀ values of 15.37 ± 0.46 µg mL^-1 in HepG2 cells and 52.64 ± 1.33 µg mL^-1 in HGC-27 cells. <b>Conclusions:</b> The workflow identified three preliminary alkaloid hits, with <b>CID 101691758</b> showing the most favorable combined computational and cell-viability profile. However, the MTT assay does not establish direct CDK2 inhibition or kinase selectivity. Biochemical CDK2 inhibition, target-engagement, and kinase-panel studies are therefore required.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Incretin-Based Therapies on Testosterone Levels and Incretin Response in Men with Hypogonadism: A Systematic Literature Review Following PRISMA 2020 Guidelines.","authors":"Sandro La Vignera, Rosita Condorelli","doi":"10.3390/ph19081321","DOIUrl":"10.3390/ph19081321","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Male hypogonadism affects 35-50% of men with type 2 diabetes mellitus (T2DM) and obesity. The relationship between testosterone deficiency and response to incretin-based therapies (GLP-1 and GIP receptor agonists) remains incompletely understood. This systematic literature review, conducted following PRISMA 2020 guidelines, examines whether male hypogonadism represents a risk factor for poor response to incretin therapy or, conversely, whether these agents offer therapeutic benefits for this population. &lt;b&gt;Methods&lt;/b&gt;: A comprehensive systematic literature search was conducted on 31 December 2024, across PubMed/MEDLINE, Scopus, and Web of Science using three search domains: (1) hypogonadism and incretin therapy response; (2) testosterone deficiency and GLP-1/GIP receptor agonists; (3) incretin response and testosterone. Eligibility criteria included human studies (randomized controlled trials [RCTs], observational studies, cohort studies, cross-sectional studies, systematic reviews, and meta-analyses) in adult men reporting testosterone levels and/or incretin response. Animal studies, pediatric populations, case reports with &lt;i&gt;n&lt;/i&gt; &lt; 5, editorials, and letters without data were excluded. Study selection followed PRISMA 2020 guidelines with independent dual screening. Risk of bias was assessed using the Cochrane Risk-of-Bias 2.0 tool (ROB2) for RCTs, the Newcastle-Ottawa Scale (NOS) for observational studies, and AMSTAR-2 for systematic reviews and meta-analyses. Due to substantial heterogeneity in study designs, populations, interventions, and outcome measures, a meta-analysis was not feasible; therefore, a narrative synthesis was performed. &lt;b&gt;Results&lt;/b&gt;: From 326 records identified, 29 studies were included after deduplication and screening (primary studies: 14; systematic reviews/meta-analyses: five; narrative reviews/expert opinion: 10). Risk-of-bias assessment revealed moderate-to-high overall risk: RCTs had small sample sizes (&lt;i&gt;n&lt;/i&gt; = 12-42) and short follow-up (12-24 weeks), raising concerns about statistical power; observational studies were of fair-to-good quality (NOS 4-7 stars) but subject to confounding; and systematic reviews were of low-to-moderate confidence (AMSTAR-2). Primary evidence from RCTs and observational studies demonstrates that GLP-1 receptor agonists (GLP-1RAs)-particularly semaglutide and liraglutide-and the dual GIP/GLP-1 receptor agonist tirzepatide significantly increase total testosterone levels in men with obesity-related functional hypogonadism (mean increase 2.5-5.2 nmol/L). This effect is largely mediated by weight loss and improvement of insulin resistance rather than direct androgenic action. Evidence regarding whether baseline hypogonadism impairs glycemic or weight-loss response to incretin therapy is limited and indirect; no adequately powered comparative trials stratified by baseline testosterone status were identified. &lt;b&gt;Conclusions&lt;/b&gt;: Incretin-based therapie","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable Multi-Isoform QSAR, PubChem Concordance, and Applicability-Domain-Guided Prioritization of Selective Human Carbonic Anhydrase I, II, IX, and XII Inhibitors.","authors":"Alaa M Elsayad, Khaled A Elsayad","doi":"10.3390/ph19081322","DOIUrl":"10.3390/ph19081322","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Human carbonic anhydrase (CA) isoforms are clinically relevant zinc metalloenzymes, but their highly conserved catalytic Zn²⁺ site makes isoform-selective inhibitor design challenging. This study developed an explainable multi-isoform QSAR workflow for prioritizing selective inhibitors of human CA I, CA II, CA IX, and CA XII, integrating PubChem experimental concordance and applicability-domain (AD) analysis to distinguish model-supported candidates from exploratory extrapolative hypotheses. <b>Methods:</b> Curated ChEMBL <i>K_i</i> datasets were standardized to <i>pK_i</i> and modeled in KNIME using 4185 two-dimensional descriptors, Random Forest-based feature selection, and H2O.ai AutoML stacked ensembles. A matched 3200-compound four-isoform matrix supported direct selectivity profiling. Potent ChEMBL inhibitors (<i>K_i</i> < 10 nM) seeded 90% PubChem similarity expansion; analogues were scored across all four isoform-specific models, while PubChem records were filtered to retain only human isoform-specific <i>K_i</i> evidence. AD was calibrated using Morgan fingerprint similarity, descriptor-space distance, and leverage analysis. Candidates were prioritized by predicted potency, selectivity, SAR plausibility, SwissADME profile, structural alerts, and AD membership. <b>Results:</b> Models achieved held-out R² values of 0.727, 0.719, 0.652, and 0.607 for CA I, CA II, CA IX, and CA XII, respectively. PubChem concordance identified 1098 prioritized compounds with assay records, including 847 with direct <i>K_i</i> evidence and 428 with complete four-isoform coverage; same-target agreement showed Pearson r > 0.86 and linear-fit R² > 0.74. Test-set error rose from very-high-AD to low/out-of-domain classes. <b>Conclusions:</b> The workflow integrates QSAR prediction, PubChem concordance, explainable SAR, ADME triage, and AD-based reliability assessment. CA II and CA XII candidates showed the strongest support, CA IX showed intermediate support, and CA I candidates require cautious interpretation as low-domain exploratory hypotheses.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13517064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticulate and Hydrogel Vehicles for Stimuli-Responsive and Sustained Controlled Release of Active Pharmaceutical Ingredients.","authors":"Simona Ardelean, Ioana Ciopănoiu, Ioana Cuc-Hepcal, Anda O J Samoila, Corina Morodan, Mihaela Borlea, Silviu L Constantinescu, Oana Koppandi, Sorina Ciurlea, Carmen Tomoroga, Adriana Ledeți, Livia C Borcan, George A Drăghici, Paul Albu, Cristina A Dehelean","doi":"10.3390/ph19081324","DOIUrl":"10.3390/ph19081324","url":null,"abstract":"<p><p>Most active pharmaceutical ingredients (APIs) reach their target by passive systemic distribution, so the dose required for efficacy at the lesion is set by what healthy tissue can tolerate; conventional dosage forms consequently produce pharmacokinetic profiles that oscillate between toxic peaks and sub-therapeutic troughs. Nanoparticulate carriers (liposomes, lipid nanoparticles, polymeric and inorganic systems, and biomimetic carriers) and hydrogels (natural, synthetic, supramolecular, and microgel-assembled) have emerged as the dominant strategies to address this, increasingly combined as hybrid nanoparticle-hydrogel constructs in which the gel provides locoregional retention and the nanoparticles provide cargo protection, intracellular delivery and stimuli responsiveness. Stimuli-responsive chemistries (pH, redox, enzyme, ROS, hypoxia, temperature, light, magnetic, ultrasound, glucose, and multi-stimuli logic) translate the molecular signatures of a disease into spatiotemporally controlled cargo release. This narrative review consolidates the state of the art (prioritizing 2022-2026) and departs from the conventional carrier-type survey in one respect: the literature is read along an explicit chain-disease cue, sensing chemistry, carrier architecture, release mechanism and kinetics, administration route, and clinical readiness-which exposes a variable that classification by carrier type conceals. Across all three material classes, what governs release behavior is not primarily the carrier chemistry but the identity of the released species (dissolved drug, drug from an embedded nanoparticle, an intact nanoparticle, and a matrix fragment) and the transport step that limits it. This is why power-law exponent analysis developed for dissolved drug fits particulate release poorly, why statistical goodness-of-fit cannot by itself establish a release mechanism, and why carrier class predicts clinical readiness less well than administration route and regulatory product type. Translational hurdles-CMC complexity, regulatory fragmentation, anti-PEG immunogenicity, and the structural mismatch between preclinical promise and clinical efficacy-are critically appraised in light of previously reported <1% delivery efficiency analysis. This review identifies converging strategies that could move stimuli-responsive controlled release from an aspirational outcome to a routine clinical reality.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review.","authors":"Caterina Nela Dumitru, Teodora Marcu, Alina Oana Dumitru, Simona Steliana Tudor, Ionela Daniela Ferțu, Alina-Mihaela Elisei, Larisa Goroftei","doi":"10.3390/ph19081313","DOIUrl":"10.3390/ph19081313","url":null,"abstract":"<p><p><b>Background:</b> Berberine, an isoquinoline alkaloid present in <i>Berberis</i> spp., <i>Coptis chinensis</i> and <i>Hydrastis canadensis</i>, is among the most widely consumed metabolic-health supplements, popularized as \"nature's Ozempic\". Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. <b>Objective:</b> To synthesize the evidence on berberine as a perpetrator of supplement-drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. <b>Methods:</b> Structured narrative review, prepared per the SANRA quality criteria; PubMed/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. <b>Results:</b> Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. <b>Conclusions:</b> In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13516377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomedical Properties, Developments and Therapeutic Potential of Sesquiterpenoid Lactones and Natural Compounds.","authors":"Normand García-Hernández, Israel Ramírez-Sánchez, Rosa María Ordoñez-Razo","doi":"10.3390/ph19081318","DOIUrl":"10.3390/ph19081318","url":null,"abstract":"<p><p>The study of plant-derived secondary metabolites has advanced the field of pharmacochemistry [...].</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13517038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid Ammonium-M(II) Hydrogenophosphite Hydrates as Bioactive Metal Complexes: Synthesis, DFT and Hirshfeld Surface Analysis, and Anticancer and Anti-Inflammatory Activities.","authors":"Zineb Ariba, Houda Zentar, Mohammed Zerrouk, Safaa Hidaoui, Mohammed Er-Rajy, Meryem Hrimla, Mustapha Ait El Had, Rachid Chahboun, Juan Sainz, Rachid Ouarsal, Mohammed Lachkar, Fernando J Reyes-Zurita","doi":"10.3390/ph19081315","DOIUrl":"10.3390/ph19081315","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Metal-based coordination compounds are attracting attention in medicinal inorganic chemistry because changes in the metal centre can influence their physicochemical properties and biological responses. This study aimed to evaluate two isostructural ammonium-M(II) hydrogenophosphite hydrates, (NH₄)₂[Mg(H₂O)₆]₃(HPO₃)₄ (complex <b>1</b>) and (NH₄)₂[Co(H₂O)₆]₃(HPO₃)₄ (complex <b>2</b>), as bioactive systems with potential anticancer and anti-inflammatory properties. <b>Methods:</b> The complexes were synthesized and characterized by X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), density functional theory (DFT) calculations, and Hirshfeld surface analysis. Their cytotoxic activity was evaluated against B16-F10, HT29, HepG2, and HL-60 tumour cell lines. For complex <b>2</b>, apoptosis, cell-cycle distribution, and mitochondrial membrane potential were analysed by flow cytometry. Nitric oxide production was measured in LPS-stimulated RAW 264.7 macrophages. <b>Results:</b> Complex <b>2</b> showed the highest cytotoxic activity, particularly against HL-60 leukaemia cells (IC₅₀ = 36.98 μg/mL), whereas complex <b>1</b> displayed weaker activity. Complex <b>2</b> increased apoptotic cell populations, altered cell-cycle distribution, and induced mitochondrial membrane depolarization in HL-60 cells. Both complexes reduced nitric oxide production, with complex <b>2</b> showing the strongest effect (IC₅₀ NO = 22.46 μg/mL), exceeding that of diclofenac under the experimental conditions, while complex <b>1</b> showed comparable activity to the reference drug. DFT descriptors indicated higher electronic reactivity for complex <b>2</b>. <b>Conclusions:</b> Replacement of Mg(II) by Co(II) enhances the biological activity of this hydrogenophosphite framework. Complex <b>2</b> combines cytotoxic activity against HL-60 cells with apoptosis-associated mitochondrial dysfunction and NO-inhibitory activity in activated macrophages, supporting hydrogenophosphite-based metal complexes as bioactive coordination compounds with potential as multifunctional agents.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"19 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13517049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}