Frontiers in Pharmacology最新文献

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal interstitial lung disease characterized by persistent alveolar injury, inflammation, and extracellular matrix remodeling, ultimately leading to respiratory failure. Despite ongoing research, current therapeutic options for IPF remain limited, underscoring the urgent need for novel treatment strategies. Methods: In this study, we investigated the pharmacological mechanisms of Polygonatum odoratum (PO) in treating IPF. We employed Weighted Gene Coexpression Network Analysis (WGCNA) and network pharmacology to identify potential therapeutic targets. Molecular docking and molecular dynamics simulations were conducted to evaluate the binding affinities and structural stability of key bioactive compounds. Subsequently, experimental validation was performed using a cellular model of bleomycin-induced pulmonary fibrosis. Results: Network analysis identified central carbon metabolism and the PI3K-Akt signaling pathway as key associated pathways. Molecular docking demonstrated that bioactive compounds of PO (including MOL010412 and MOL000332) exhibited strong binding affinities to core targets such as EGFR, BCL2, MTOR, HIF1A, and GSK3B. Experimental results confirmed that MOL000332 (n-coumaroyltyramine) significantly mitigated pulmonary fibrosis by suppressing the protein expression levels of EGFR, HIF1A, and GSK3B. Discussion: These findings suggested that PO exerted its therapeutic effects through the modulation of multiple targets and pathways, positioning it as a promising candidate for IPF treatment. This study provided a robust scientific foundation for further exploration and development of PO-based therapies for IPF.

[This corrects the article DOI: 10.3389/fphar.2026.1708101.].

Background: The continuation of hydroxychloroquine (HCQ) during pregnancy in patients with systemic lupus erythematosus (SLE) is a cornerstone of management, proven to mitigate maternal disease flares. However, its precise role in preventing the devastating cardiopulmonary complication of pregnancy-associated pulmonary arterial hypertension (PAH) remains inadequately defined, and the underlying pharmacological mechanisms remain largely elusive.

Case presentation: We detail the case of a 31-year-old primigravida with a 15-year history of well-controlled SLE, who self-discontinued HCQ at 8 weeks of gestation. At 27 + 4 weeks, she presented with significant exertional dyspnea. Diagnostic evaluation confirmed severe PAH (estimated PASP 107 mmHg) with right heart strain, alongside serological evidence of active SLE, including hypocomplementemia. A multidisciplinary therapeutic protocol was immediately instituted, comprising the reinstatement of HCQ and the administration of intravenous methylprednisolone. This intervention resulted in a marked reduction in pulmonary arterial pressure to a moderate range (PASP 73 mmHg), stabilizing the patient's condition sufficiently to prolong gestation to 31 + 1 week, culminating in a planned cesarean delivery. At the 3-month postpartum assessment, echocardiography documented sustained improvement, with PAH decreased to a mild grade (PASP 40 mmHg).

Conclusion: This case provides compelling in vivo evidence that non-adherence to HCQ constitutes a pivotal, modifiable risk factor for the onset of SLE-associated PAH in the gravid state, and that pharmacological reintroduction can arrest and partially reverse this pathogenic trajectory. We attribute the vascular protective effects of HCQ to the inhibition of complement activation along the C5a-MAPK/ERK signaling axis. Targeting this pathway disrupts pathological endothelial-mesenchymal transition (EndMT) and mitigates subsequent pulmonary vascular remodeling. Stringent HCQ adherence should be standard of care. Furthermore, complement monitoring guides precision pharmacotherapy to prevent PAH in susceptible SLE pregnancies.

Curcumin, a polyphenolic compound derived from the turmeric rhizome (Curcuma longa), has attracted significant interest in dentistry and oral medicine because of its multifaceted therapeutic properties. In particular, curcumin exhibits potent anti-inflammatory, antioxidant, and antimicrobial activities that are relevant to a wide spectrum of oral diseases. We conducted a narrative search of PubMed (2000-2025) using iterative keyword combinations related to curcumin and oral diseases/mechanisms, screened reference lists, and selected studies on the basis of their relevance to oral pathobiology, delivery systems, and clinical/translational outcomes. This narrative review summarized the current knowledge concerning the molecular mechanisms of curcumin and its clinical applications in oral health. We outlined how curcumin modulates key inflammatory pathways and oxidative stress responses, and how it exerts broad-spectrum antimicrobial effects against oral pathogens. We detailed the efficacy of curcumin in specific oral conditions, including periodontal diseases, dental caries, recurrent aphthous stomatitis, oral lichen planus, oral submucous fibrosis, oral candidiasis, radiation/chemotherapy-induced oral mucositis, and oral cancers. In each context, we highlighted evidence from in vitro studies, animal models, and clinical trials, and noted the benefits of curcumin, such as reduced inflammation, enhanced healing, microbial inhibition, and in some cases outcomes comparable to those of standard therapies. Across conditions, curcumin shows adjunctive benefit: In periodontal disease, it reduces plaque and gingival inflammation comparable to chlorhexidine and improves probing outcomes when added to scaling and root planing; in recurrent aphthous stomatitis, it reduces pain and ulcer size with steroid-like efficacy; in radiotherapy/chemotherapy-induced oral mucositis, it delays onset and decreases severity; in oral candidiasis, it decreases fungal burden and enhances photodynamic therapy; and in oral squamous cell carcinoma early clinical studies show modulation of inflammatory cytokines and the oral microbiome. Various delivery systems developed to overcome the poor bioavailability of curcumin-from mouthwashes and gels to nanocarriers and mucoadhesive formulations-are reviewed. Although many studies reported promising results with minimal toxicity or side effects, there were study limitations such as small sample sizes, variability in formulations, and the pharmacokinetic properties of curcumin. Overall, the reviewed data support the role of curcumin as a safe, formulation-dependent adjunct-not a stand-alone therapy-in oral medicine.

Background: For decades, cough treatment has relied on centrally acting agents like codeine despite inconsistent efficacy. Advances in cough neurobiology enabled targeted therapies. Natural remedies remain widely used, though evidence for their effectiveness and safety is limited. This study aimed to compare evidence on the efficacy and safety of conventional, natural, and novel antitussives.

Methods: A systematic review and meta-analysis of randomized clinical trials assessed cough frequency, Visual Analogue Scale (VAS), Leicester Cough Questionnaire (LCQ) and adverse events versus placebo.

Results: Subgroup meta-analysis showed no significant differences between P2X3 antagonists, indicating a consistent class effect. All subgroups reduced chronic cough frequency [standardized mean difference (SMD) = -0.50, 95% confidence interval (CI) (-0.67-0.34), P = 0.0001], suggesting that the observed effect is a class-related response rather than a compound-specific effect.

Conclusion: Conventional and natural antitussives show inconsistent efficacy. P2X3 receptor antagonists appear most promising, marking a shift beyond codeine toward targeted chronic cough therapies.

Clinical trial registration: The meta-analysis was performed according to the protocol described in PROSPERO, identifier CRD420251172660.

Background: Candida species are major opportunistic pathogens, with Candida albicans being the most frequent cause of candidiasis. However, increasing rates of non-albicans infections and antifungal resistance bring an urgent need for new therapeutics. Essential oils (EOs) have gained attention due to their potential to inhibit fungal growth and virulence.

Methods: The chemical composition of cinnamon, thyme and clove EOs was analyzed by gas chromatography-mass spectrometry (GC-MS). Antifungal activity was evaluated against eighteen Candida strains representing nine species, including multidrug-resistant isolates. Minimum inhibitory concentrations (MICs) were determined. The two most active EOs were further assessed for their effects on germ tube formation and protease production, two key virulence traits.

Results: GC-MS identified cinnamaldehyde, thymol and eugenol as the dominant components of cinnamon, thyme and clove EOs, respectively (> 70% relative abundance). All EOs displayed antifungal activity, with cinnamon and thyme being the most potent. Both oils showed increased activity against multidrug-resistant strains of Candida parapsilosis and Nakaseomyces glabratus compared with their susceptible parentals, suggesting they may target resistance trade-offs. All five clades of Candidozyma auris displayed low MICs for cinnamon EO (0.002-0.008% v/v), indicating high susceptibility. Cinnamon EO reduced germ tube formation in C. albicans from 97% to 12% at MIC/2, while thyme EO completely inhibited germ tube formation and induced pseudohyphae. Protease production was totally suppressed in C. auris clades II and III at MIC/2 thyme EO.

Conclusion: These results highlight the strong dual activity of EOs, supporting further exploration of their potential as complementary therapeutic options against Candida infections.

Neurological disorders like Alzheimer's, Parkinson's, multiple sclerosis, and primary psychiatric conditions are complex, arising from a mix of genetic and modifiable risks. Growing evidence indicates that nutrition, environment, and lifestyle significantly influence disease development, progression, and treatment response. Nutrients such as vitamins, minerals, omega-3 fatty acids, and polyphenols affect neuroinflammation, oxidative stress, mitochondrial health, and neurotransmitter function. Dietary patterns like the Mediterranean and ketogenic diets offer protective benefits in clinical and experimental contexts. Meanwhile, environmental neurotoxicants-air pollution, heavy metals, pesticides, and endocrine disruptors contribute to neurodegeneration via oxidative damage, synaptic impairment, and epigenetic alterations. Lifestyle factors, such as physical activity, sleep, stress, and substance use, affect brain plasticity, neurogenesis, and metabolic health, thereby influencing disease progression over time. These factors often share common pathways such as oxidative stress, inflammation, vascular injury, mitochondrial dysfunction, and protein misfolding, underscoring the need for a comprehensive prevention and treatment strategy. Emerging therapies now incorporate personalized nutrition, lifestyle changes, and environmental risk mitigation alongside traditional drugs, supported by advances in multi-omics, digital health, and systems biology. Public health efforts to reduce neurotoxic exposure and encourage healthy habits further strengthen these approaches. This review summarizes existing mechanistic and clinical knowledge, with a focus on the potential of nutritional, environmental, and lifestyle interventions in neurological diseases. It also outlines the future research required to enhance precision neurology and strategies for brain health prevention.

Luteolin is a natural flavonoid compound widely found in various plants, known for its antioxidant, anti-inflammatory, cardiovascular protective and anti-tumor activities. However, its low bioavailability due to rapid metabolism and low solubility hinders its clinical application. In recent years, with the development of nanotechnology, luteolin combined with nanomaterials to form nanocomposites has shown promising drug delivery performance and therapeutic effects in numerous diseases. This article reviews the latest research progress on luteolin nanocomposites in disease treatment, exploring their potential applications in cancer, diabetes, cardiovascular diseases, neurological disorders, and other conditions.