Frontiers in Pharmacology药理学前沿
Frontiers in Pharmacology(英文缩写 FRONT PHARMACOL),ISSN 1663-9812,eISSN 1663-9812,中文译名:药理学前沿 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-10-01 至 2026-09-30，按本站收录文献的发表日期统计。
期刊介绍
Frontiers in Pharmacology 最新收录文献
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1. Mechanism-aware and safety-validated AI for drug repurposing: a critical review and translational pharmacology framework.
PMID:日期:2026-09-18Artificial intelligence (AI)-assisted drug repurposing seeks to identify new therapeutic applications for existing drugs. Nevertheless, most of the existing studies are centered on prediction scores and candidate ranking, and there is still relatively little attention paid to the pharmacological mechanisms, safety and translational validation. This critical review summarizes existing AI approaches to drug repurposing, identifies their mechanistic, safety, and translational barriers, and incorporates the emerging evidence gaps into a mechanism-driven and safety-proven translational pharmacology model. The literature reviewed shows that machine learning, deep learning, network medicine, knowledge graphs, graph neural networks, and foundation models have the potential to significantly increase the number of candidates identified, but they have marked variations in terms of interpretability, biological support, safety integration, external validation, and clinical applicability. In all of these strategies, common shortcomings are inadequate mechanism validation, poor causal evidence, incomplete dose and safety evaluation, weak pharmacovigilance integration, and reliance on internal validation, and varying experimental or real-world confirmatory evidence. These persistent evidence gaps were incorporated into a sequence of steps that incorporates candidate predictions, mechanism mapping, determination of causal plausibility, safety and toxicity evaluation, pharmacovigilance, real-world validation, expert pharmacology review and evidence-based candidate prioritization. AI-driven drug repurposing presents huge potential in the field of therapeutic innovation, but current applications require more clinical evidence and pharmacological mechanisms demonstrating safety, as well as clinical relevance. The proposed framework can support the more reliable prioritization of candidates for experimental testing, real world validation and future clinical testing.
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2. Review Areca Thirteen Pill (GY-13) for depression: a ConPhyMP-Informed critical review of material definition, pharmacological evidence, and translational Heyi-neuroplasticity-stress hypotheses.
PMID:日期:2026-09-18Previous summaries of GY-13 have lacked transparent literature-search methods, reproducible material definitions, chemical-characterization status, or critical evidence grading, limiting their scientific utility. This review critically evaluates what the published GY-13 literature shows and does not show regarding antidepressant pharmacology, material reproducibility, clinical evidence, and safety. It also reformulates the Heyi-Neuroplasticity-Stress (HNS) framework as a testable translational hypothesis rather than as a confirmed mechanism. This critical scoping review was reported using a PRISMA-informed approach, with PRISMA-ScR, the Four Pillars of Best Practice in Ethnopharmacology, and ConPhyMP used as reporting and interpretive frameworks. Searches were rerun on 3 June 2026 in PubMed/MEDLINE and CNKI, supplemented by public bibliographic records and citation checking. Thirty records were identified; after deduplication and screening, 12 studies or contextual records were retained. The review was not prospectively registered, screening and extraction were not performed by two independent reviewers, and no validated design-specific risk-of-bias tool was applied. These limitations preclude designation as a fully systematic review. The available evidence supports the possibility that GY-13 affects depression-related behavioral and molecular endpoints in stress-based animal models, including cAMP/PKA/CREB/BDNF signaling, HPA-axis feedback, monoamine signaling, inflammatory-oxidative pathways, and chemokine-axis findings. However, the reproducibility of these findings is limited by incomplete reporting of batch identity, voucher/authentication data, manufacturing details, HPLC/UPLC or LC-MS fingerprints, marker-metabolite quantification, dose-response structure, and randomization/blinding. Human evidence remains preliminary and insufficient for definitive clinical-efficacy claims. GY-13 is best treated as a hypothesis-generating multi-component intervention requiring chemically defined batches, strict ConPhyMP documentation, independent preclinical replication, and well-powered clinical trials with standardized safety monitoring. The HNS framework may guide future biomarker-enriched research only if tested prospectively with transparent materials and methods.
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3. {"_":"Carvacrol exhibits potent anti- activity, whereas the multicomponent composition of essential oils may contribute to their enhanced antibacterial activity.","i":["Klebsiella"]}
PMID:日期:2026-09-18Multidrug-resistant (MDR) infections represent an increasing therapeutic challenge, underscoring the need for complementary antimicrobial strategies. Essential oils (EOs) are complex mixtures of bioactive compounds, and their antibacterial effects may not be fully explained by their predominant constituents. We compared the antibacterial activity of isolated carvacrol with that of oregano (), summer savory (), and thyme () essential oils against MDR isolates and evaluated their ability to enhance conventional antibiotics. Essential oils were chemically characterized by gas chromatography-mass spectrometry (GC-MS). Antibacterial activity was evaluated by agar diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Interactions with ceftazidime, gentamicin, and ciprofloxacin were assessed using full checkerboard assays and fractional inhibitory concentration indices (FICIs). Toxicity was evaluated in and larvae. GC-MS identified carvacrol as the predominant constituent of oregano (71.47%) and summer savory (48.83%) oils, whereas thyme oil contained low levels of carvacrol (1.83%). Whole oregano and summer savory oils exhibited greater bactericidal activity than isolated carvacrol in several comparisons, despite the high carvacrol content of these oils. Thyme oil also showed substantial antibacterial activity despite its low carvacrol concentration, indicating that activity was not determined solely by carvacrol abundance. Toxicity assays indicated low toxicity for carvacrol, oregano, and thyme oils under the tested conditions, whereas summer savory showed moderate, species-dependent toxicity. Overall, whole essential oils exhibited antibacterial activities that could not be explained solely by their carvacrol content, supporting a contribution of their multicomponent phytochemical composition. Their ability to potentiate conventional antibiotics further supports their potential as complementary antimicrobial agents against MDR . Further studies using purified constituents and defined combinations are warranted to determine the specific mechanisms underlying these effects.
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4. {"_":"Public knowledge, safety perceptions, and use patterns of ashwagandha () among Saudi adults: a mixed-methods study.","i":["Withania somnifera"]}
PMID:日期:2026-09-18, commonly known as ashwagandha, is a widely used herbal remedy with reported anxiolytic and adaptogenic properties. Despite its growing use globally and regionally, comprehensive public understanding of its pharmacological benefits, safety, and potential risks remains limited within the Saudi Arabian context. This study aimed to evaluate knowledge, safety perceptions, pharmacological awareness, and patterns of ashwagandha use among Saudi adults using a mixed-methods approach. A convergent mixed-methods design was employed, incorporating a cross-sectional survey of 508 participants and semi-structured interviews with 20 participants. Data were collected over a 6-month period from August 2025 to January 2026. Quantitative data were analyzed using descriptive statistics, inferential tests, and multiple linear regression analyses to identify predictors of knowledge and attitudes. Qualitative data were thematically analyzed to explore participants' experiences, motivations, and safety concerns. Quantitative and qualitative findings were integrated during the interpretation phase. Overall knowledge and pharmacological awareness of ashwagandha were limited, with nearly half of the participants demonstrating low knowledge levels. Social media and informal networks were the primary sources of information, whereas healthcare professionals were rarely consulted. Positive perceptions of ashwagandha were associated with previous use, frequent use, and a self-reported history of anxiety-related symptoms or conditions. Qualitative findings indicated that ashwagandha use was generally sporadic and motivated by stress management. Participants commonly described cautious, self-regulated use because of concerns about side effects and long-term safety. Some participants also reported using ashwagandha concurrently with other herbal supplements or dietary supplements, raising concerns about potential supplement-supplement interactions and cumulative adverse effects. Ashwagandha use among Saudi adults appears to be influenced primarily by personal experience and psychological factors rather than formal knowledge or professional guidance. Reliance on informal information sources, limited pharmacological awareness, and concerns regarding the safety of combining herbal supplements highlight the need for targeted public health education and greater involvement of healthcare professionals. These findings emphasize the importance of improving public understanding of the pharmacological properties, potential risks, interactions, and safe use of herbal medicines.
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5. Integrating network analysis and machine learning to explore the pharmacological targets and associations of oleanolic acid in lung adenocarcinoma.
PMID:日期:2026-09-18Lung adenocarcinoma (LUAD), a major type of non-small cell lung cancer, has high incidence and mortality rates. Oleanolic acid (OA), a natural pentacyclic triterpene compound, has demonstrated potential anti-tumor effects but its pharmacological effects in LUAD remain unclear. This study aims to identify the potential targets and action pathways of OA in LUAD using network analysis, transcriptomics, molecular docking, animal experiments, and preliminary clinical sample assessment. Potential candidate genes for OA in LUAD were identified from public databases including PubChem, GeneCards, and TCGA. GO and KEGG enrichment analyses were performed using Metascape, and a PPI network was constructed. Machine learning methods (Lasso regression and SVM-RFE) were employed to refine the candidate genes and identify key biomarkers. Prognostic, clinicopathological, GSEA, mutation, and immune infiltration analyses were conducted. Molecular docking was performed to estimate the theoretical binding affinity between OA and the biomarkers, which was further evaluated using animal models and clinical samples. 21 candidate genes were initially identified, with TOP2A and ALOX5AP emerging as key biomarkers. High TOP2A expression and low ALOX5AP expression were associated with poor prognosis. GSEA showed co-enrichment in the IgA production pathway. Mutation analysis indicated higher amplification propensity for TOP2A. Both biomarkers correlated with immune cells. Molecular docking and animal experiments suggested OA's regulatory effects on these genes, with clinical sample evaluation. Utilizing computational screening as a theoretical starting point alongside preliminary experimental evaluations, this study identifies ALOX5AP and TOP2A as potential pharmacological biomarkers associated with OA treatment in LUAD. Rather than asserting definitive specific targeting, these findings provide preliminary associative evidence. Although direct causal relationships require further functional investigation, this work establishes a pharmacological and theoretical foundation for understanding OA's anti-tumor effects and future therapeutic potential.
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6. Early socially isolated rats of both sexes reduce alcohol consumption and seeking by the Galanin (1-15) and naltrexone combination.
PMID:日期:2026-09-18Alcohol Use Disorder (AUD) is a psychiatric condition whose severity can be amplified by social factors, such as social isolation, particularly during adolescence, which exacerbates development of AUD in adulthood. Our previous studies have demonstrated that the Galanin (1-15) fragment [GAL (1-15)] reduces alcohol seeking and consumption. Furthermore, the combination of GAL (1-15) with Naltrexone (NTX)-an approved but moderately effective treatment for AUD- potentiates reduced alcohol intake and seeking behavior, showing interaction with the opioid system. Previous studies on the effects of GAL (1-15) on AUD have been conducted mainly in male animals, leaving the effects on females largely unexplored despite the well-established sex differences in alcohol use disorder. Therefore, this study introduces early-life social isolation as a critical environmental vulnerability factor for adult alcohol abuse and evaluates these mechanisms in female subjects for the first time. Specifically, we investigate the combined effects of GAL (1-15)+NTX on alcohol consumption and seeking in male and female adolescent-isolated rats, along with associated changes in mesolimbic gene expression. In socially isolated male and female rats, we evaluated GAL (1-15)+NTX in terms of voluntary alcohol intake (two-bottle choice) and reward-seeking behavior (self-administration). We analyzed transcriptional changes in C-Fos, MOR, dopamine and galanin receptors in the ventral tegmental area and nucleus accumbens. Social isolation moderately increased ethanol intake and operant alcohol responding in both sexes. GAL (1-15)+NTX significantly reduced operant responding in isolated rats of both sexes, but reduced alcohol consumption only in males, with no significant effect in females at the tested doses. These effects were associated with alterations in C-Fos, MOR and dopamine receptor expression, suggesting that there is an association between molecular changes related to the mesolimbic and opioid systems and the observed reduction in alcohol-seeking behavior and consumption, even in a model of early social isolation. These findings suggest that GAL (1-15)+NTX could be explored further as a potential strategy in AUD research, particularly in socially vulnerable contexts.
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7. Squalene alleviates DSS-induced colitis by restoring Nrf2-dependent redox balance and gut microbiota homeostasis.
PMID:日期:2026-09-18Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by excessive oxidative stress, intestinal epithelial barrier dysfunction, and gut microbiota dysbiosis; despite expanding therapeutic options, achieving durable disease control remains challenging. Squalene (SQ), a naturally occurring triterpene with antioxidant and anti-inflammatory properties, has emerged as a promising bioactive compound. Although the protective potential of SQ in experimental colitis has been previously reported, the molecular dependence of this effect and the functional contribution of the gut microbiota remain incompletely defined. This study investigated the protective effects of SQ against DSS-induced experimental colitis and the roles of Nrf2 signaling and the gut microbiota in mediating these effects. DSS-induced colitis was established in mice to evaluate the protective effects of SQ. Disease severity, histopathological injury, oxidative stress, inflammatory responses, intestinal barrier integrity, and gut microbiota composition were assessed. Nrf2-deficient mice, pharmacological inhibition of Nrf2, antibiotic-mediated microbiota depletion, fecal microbiota transplantation (FMT), 16S rRNA sequencing, cellular thermal shift assay (CETSA), and lipopolysaccharide-stimulated Caco-2 cells were employed to investigate the underlying mechanisms. SQ markedly alleviated experimental colitis by reducing disease activity, preventing colon shortening, and improving histopathological injury. Mechanistically, SQ activated Nrf2-dependent antioxidant defense, attenuated oxidative stress, suppressed NF-κB-mediated inflammation, and restored intestinal barrier integrity by enhancing tight junction protein expression. These protective effects were substantially diminished in Nrf2-deficient mice, identifying Nrf2 as a critical mediator of SQ activity. SQ also reshaped gut microbial composition and partially restored microbial community structure. Antibiotic-mediated microbiota depletion markedly weakened the beneficial effects of SQ, whereas fecal microbiota transplantation from SQ-treated donors transferred protection against DSS-induced colitis, supporting a functional contribution of microbiota remodeling to SQ-mediated protection. Consistently, SQ suppressed inflammatory responses and restored barrier-related protein expression in lipopolysaccharide-stimulated Caco-2 cells, effects that were attenuated by pharmacological inhibition of Nrf2. CETSA further demonstrated enhanced thermal stability of Nrf2 following SQ treatment, suggesting potential target engagement between SQ and Nrf2. SQ exerts protective effects against experimental colitis primarily through an Nrf2-dependent host molecular axis, with gut microbiota remodeling providing an important complementary functional contribution. These findings identify Nrf2 as the principal molecular mediator of SQ activity and position microbiota remodeling as a complementary component of its protective effects, supporting SQ as a promising bioactive candidate for intestinal inflammatory disorders.
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8. Scutellarin attenuates high glucose-induced edema and inflammation in retinal Müller cells via AQP4/Kir4.1 restoration and TLR4/MyD88/NF-κB inhibition.
PMID:日期:2026-09-18Diabetic retinopathy (DR) is a metabolic eye disease closely linked to inflammation and oxidative stress, potentially causing vision decline or blindness. Scutellarin (SCU), a major flavonoid extracted from Erigeron breviscapus, possesses anti-inflammatory and antioxidant properties; however, its protective mechanisms against retinal Müller cell (RMC) injury in DR remain unclear. To investigate the protective effects and underlying mechanisms of SCU against high-glucose(HG)-induced edema and inflammation in retinal Müller cells (RMCs). Primary RMCs were isolated from newborn 3-5-day-old Sprague-Dawley (SD) rats and exposed 100 mmol/L HG to establish an injury model. Groups included control, model (HG), low-dose (HG+25 μmol/L SCU), and high-dose (HG+50 μmol/L SCU). Cell viability, migration capacity, Na-K-ATPase activity, and apoptosis were assessed using CCK-8 assays, scratch wound healing assays, enzymatic activity assays, and flow cytometry, respectively. The expression and distribution of AQP4, Kir4.1, and molecules associated with the TLR4/MyD88/NF-κB/VEGFA pathway were evaluated via immunofluorescence, Western blot, and qRT-PCR. HG exposure significantly suppressed RMC viability, induced apoptosis, disrupted the functional coupling of AQP4/Kir4.1, and activated the TLR4/MyD88/NF-κB/VEGFA signaling pathway. SCU treatment dose-dependently reversed these pathological changes, restored Na-K-ATPase activity and the expression balance of AQP4/Kir4.1, and inhibited the excessive activation of the inflammatory pathway. The protective effects of SCU are significantly associated with the restoration of AQP4/Kir4.1 homeostasis and the suppression of the TLR4/MyD88/NF-κB/VEGFA pathway, suggesting its potential as a multi-target candidate drug for delaying the progression of DR.
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9. Timing of nebulized colistimethate sodium following bronchodilator airway conditioning in hospital-acquired pneumonia: a target trial emulation study.
PMID:日期:2026-09-18Evidence for nebulized colistimethate sodium (CMS) in hospital-acquired pneumonia (HAP) remains inconsistent, potentially due to heterogeneity in airway conditions and delivery timing. We evaluated whether timely initiation of nebulized CMS following bronchodilator airway pre-treatment was associated with microbiological outcomes in critically ill patients. We conducted a multicenter retrospective cohort study using target trial emulation among adult ICU patients with HAP who received nebulized CMS following bronchodilator nebulization. Two per-protocol strategies were compared: initiation within 90 min of bronchodilator nebulization (LE90) versus later initiation (GT90). Cloning, censoring, and inverse probability of censoring weighting were applied to address time-dependent confounding. The primary outcome was 14-day cumulative incidence of microbiological clearance, treating death as a competing event. Among 218 eligible patients, timely initiation was associated with a higher weighted cumulative incidence of microbiological clearance at day 14 (71.9% vs. 52.6%; absolute difference 19.3%, 95% CI 4.8-32.5; = 0.012) and a shorter restricted mean time alive and not microbiologically cleared (6.85 vs. 10.08 days; difference -3.23 days, 95% CI -4.30 to -2.08; < 0.001). Findings were consistent across subgroups and robust in sensitivity analyses. No significant differences were observed in clinical success, superinfection, mortality, ICU length of stay, or ventilator-free days. Bronchospasm incidence was similar between strategies. Timely initiation of nebulized CMS within a defined post-bronchodilator window was associated with higher microbiological clearance and reduced persistent infection, without increased airway adverse events. These findings are hypothesis-generating and require prospective validation, particularly with respect to patient-centered outcomes.
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10. {"_":"Occurrence, variability and evolutionary relations of efflux pump determinants across five pathogenic species.","i":["Staphylococcus"]}
PMID:日期:2026-09-18Multidrug efflux pumps (MDR EPs) play a major role in the emergence of antimicrobial resistance in . Among these, the native NorA is the most well-studied MDR EP in this species. However, efflux-mediated resistance is only scarcely characterized in other staphylococci. The aims of this study were to assess the genetic variability and phylogenetic relations of main efflux pump genes in and four other pathogenic staphylococci, and to identify new putative MDR transporters in these species. Nucleotide sequences of , , , , and related sequences of , , , and were compiled and assessed for gene variability. The variability was further evaluated in a collection of clinical strains of , and . Phylogenetic analyses were performed to characterize the evolution of across the five species and to explore potential relations between , , and related sequences. Additional putative MDR transporter genes were searched in public databases and then BLAST searched against complete genomes of each species. Only presented several and alleles. The relations between the genes of the five species follow the evolutionary relations of these staphylococci. Phylogenetic analysis also revealed the existence of a gene in , which is homologous to the genes of , , and . It also indicated that and as well as the newly assigned are related genes, absent in the other species. analysis identified several new candidate MDR transporters in the five species. This study provides a novel, comprehensive comparative analysis of major efflux pump determinants across five clinically relevant species. This analysis expanded our knowledge of the evolutionary pathways and provided a framework for a more consistent annotation of , and related determinants among these staphylococci. The identification of putatively new MDR transporter determinants in staphylococcal species of clinical relevance other than provides a framework for future functional studies.