Frontiers in Pharmacology最新文献

Alzheimer's disease (AD) is one of the most prevalent central nervous system disorders affecting middle-aged and elderly populations. As a neurodegenerative disease, its primary clinical manifestations include memory impairment, cognitive dysfunction, and behavioral abnormalities. However, there are limited clinically available treatments for AD. Existing medications neither cure the disease nor halt its progression, and are often associated with significant side effects. Scutellaria baicalensis Georgi, with its long history of medicinal use, shows potential for treating central nervous system disorders. Modern pharmacological research has revealed its antioxidant, anti-inflammatory, antiviral, neuroprotective, and immunomodulatory properties. Its active metabolites, such as baicalin and baicalein, exert multi-target effects by simultaneously influencing Aβ production and aggregation, tau phosphorylation, and microglial activation, while also regulating brain-gut axis function. This systematic review examines the mechanisms of action of baicalin and baicalein, the active metabolites of Scutellaria baicalensis Georgi, in treating Alzheimer's disease, offering novel insights and research directions for modern medical approaches to Alzheimer's disease treatment.

Mitochondria act as a central integrative hub for oxidative phosphorylation, calcium homeostasis and metabolic signaling, reflecting their evolutionary origin from an α-proteobacterial endosymbiont. Although nearly 90% of their ancestral genes have been transferred to the nuclear genome, their role extends far beyond energy production. Emerging evidence positions mitochondria as active modulators of stress responses, which we term the "Mito-Mood Hypothesis." This framework proposes that mitochondrial dynamics actively regulate gene expression and signaling, thereby shaping vulnerability to mood disorders such as depression, dysthymia, and seasonal affective disorder. Consistent with this view, patients with major depressive disorders show altered expression of nuclear-encoded mitochondrial genes, linking bioenergetics directly to psychiatric risk. We further discuss how oxidative phosphorylation (OXPHOS) modulates neurotransmitter cycles and how mitohormesis-adaptive responses to mild mitochondrial stress-can enhance resilience and cognition. Beyond psychiatry, mitochondrial vulnerability manifests in clinical settings: patients with mitochondrial diseases face elevated anesthetic risk, where agents such as propofol or volatile anesthetics may precipitate life-threatening metabolic crises. Collectively, these insights underscore mitochondria as central regulators of human health and highlight novel therapeutic opportunities bridging mood disorders and perioperative medicine.

Background: Malanje Municipality in north-central Angola harbors exceptional botanical and cultural diversity, yet remains poorly documented for traditional medicinal plant knowledge; this study provides the first systematic ethnopharmacological baseline to guide pharmacological prioritization, conservation, and policy-relevant integration of traditional medicine.

Methods: Between 2018 and 2023, we conducted semi-structured interviews (n = 20 traditional healers), participatory observation, in situ photographic documentation, and GPS mapping. Voucher specimens were taxonomically verified against herbarium material and online resources. Quantitative indices included frequency measures and rank order priority (ROP); therapeutic indications were grouped using ICD-11 categories.

Results: Informants reported 272 ethnospecies, of which 78 taxa (39 families) were identified to species level. Fabaceae (9%), Asteraceae (6.4%), and Euphorbiaceae, Poaceae, and Zingiberaceae (each 5.1%) were most represented families. Leaves (53.8%) and roots (42.3%) were the principal parts used; decoction (60%) and maceration (31%) were the most common preparations. ROP prioritized Terminalia brachystemma (81.8), Securidaca longepedunculata (54.4), and Mondia whitei (52.2) for follow-up study. Treated conditions clustered in gastrointestinal disorders (43.6%) and infectious/parasitic diseases (29.5%). Healers reported several contraindications and observable adverse effects.

Conclusion: This work provides the first comprehensive ethnopharmacological register for Malanje Municipality, highlighting high-priority species for phytochemical, pharmacological, and toxicological evaluation and identifying conservation and sustainable-use concerns (notably root harvest). Limitations include a modest sample of informants and incomplete taxonomic resolution for many ethnospecies.

Recommendations: Expand sampling across the province, complete voucher identification, perform contamination and toxicity screening, and develop community-led cultivation and stewardship plans that align with Angola's National Policy for Traditional and Complementary Medicine.

[This corrects the article DOI: 10.3389/fphar.2025.1520136.].

Background: Immune-mediated inflammatory diseases (IMIDs) often affect women of childbearing age. Since active inflammatory disease is related with impaired reproductive outcomes, effective disease control is crucial. Clinical guidelines aim to support evidence-based shared decision-making. However, inconsistencies between guidelines across specialties may cause confusion, undermine adherence and lead to adverse health outcomes. This study aimed to assess consistency within and across perinatal IMID guidelines in gastroenterology, rheumatology and dermatology regarding medication use during pregnancy, lactation and among prospective fathers, and to identify medications with insufficient safety data.

Methods: A review was conducted in August 2025 using most recent versions of leading international guidelines (N = 11), published between 2015 and 2025. Guideline recommendations for IMID medications were categorized by two independent authors. Data-analysis examined the prevalence and type of consistency, trimester-specific consistency, most common recommendation per medication and the agreement on preconception discontinuation timing.

Results: Within medical specialties, guideline consistency for individual medications was highest for gastroenterology (61/74, 82.4%), followed by rheumatology (165/220, 75.0%) and dermatology (57/94, 60.6%). Across specialties, agreement was greatest between gastroenterology and rheumatology (pregnancy 86.2%, lactation 81.2%, paternal 88.5%) and lowest between gastroenterology and dermatology (pregnancy 51.3%, lactation 40.6%, paternal 47.1%). Trimester-specific recommendations were consistent across guidelines in 33.3% (2/6) of the cases. Agreement on preconception discontinuation timing was 41.7% (5/12) for maternal cases and 66.7% (2/3) for paternal exposure. At least one inconsistency was found in 75.0% of within-guideline and 87.5% of across-guideline comparisons. At medication-class level, most inconsistencies stemmed from insufficient safety data reporting (59.5%), particularly for small molecules (28.6%), immunomodulators (26.1%) and interleukin inhibitors (34.1%).

Conclusion: Inconsistencies between guidelines, both within and across specialties, were frequent and pose challenges for reproductive decision-making in IMID patients. The lack of safety data in reproductive contexts contributed to guideline inconsistencies and revealed the need to prioritize future research on recently marketed pharmacotherapeutic classes, such as small molecules (JAK-inhibitors, PDE4-modulators) and interleukin inhibitors. In the future, guidelines should be updated regularly, include explicit recommendations, integrate reproductive contexts, and adopt unambiguous language, standardized categories and uniform methodological frameworks.

Lung cancer remains a leading cause of cancer mortality worldwide, with current treatments often limited by toxicity and resistance. Dysregulated kinase signaling particularly involving EGFR, PI3K/AKT/mTOR, MAPK, and ALK pathways drives tumor growth, survival, and metastasis. While synthetic kinase inhibitors have improved outcomes, their use is constrained by adverse effects and acquired resistance. Natural kinase inhibitors (NKIs) derived from plants, marine organisms, and microorganisms offer a promising alternative due to their multi-targeted action, lower toxicity, and potential to overcome resistance. This review aims to evaluate the molecular mechanisms, therapeutic potential, and clinical relevance of NKIs in lung cancer management. Key compounds such as curcumin, resveratrol, quercetin, genistein, and epigallocatechin gallate inhibit critical kinases, modulating pathways that regulate proliferation, apoptosis, angiogenesis, and metastasis. Preclinical studies demonstrate significant anticancer activity, while emerging clinical evidence supports their role as adjuncts or alternatives to conventional therapies. Strategies such as nanotechnology-based delivery systems and combination regimens further enhance bioavailability and efficacy. Despite these advantages, challenges persist, including poor solubility, rapid metabolism, and limited clinical validation. Future research should focus on optimizing formulations, elucidating pharmacokinetics, and conducting large-scale clinical trials to confirm safety and effectiveness. Integration of NKIs into personalized treatment paradigms could transform lung cancer therapy, offering cost-effective, less toxic, and multi-targeted approaches to improve patient outcomes.

Background: Hypertension (HTN) remains a major contributor to cardiovascular morbidity and mortality in the United States (US). The 2017 ACC/AHA HTN guidelines introduced major changes to diagnostic thresholds and treatment recommendations, including earlier pharmacological initiation and greater emphasis on combination therapy. However, the long-term, population-level impact of these guidelines on antihypertensive medication utilization in the US remains uncharacterized.

Methods: We conducted a pooled cross-sectional study using data from the Medical Expenditure Panel Survey (2013-2022). Adults ≥18 years with diagnosed HTN were included. Antihypertensive classes utilization was defined as any use of the medication class with ≥2 prescription refills within the same year among eligible participants. Utilization of antihypertensive classes was then pooled and examined across two periods: pre-guidelines (2013-2017) and post-guidelines (2018-2022). Survey-weighted multivariable logistic regression models were used to assess the impact of the 2017 ACC/AHA guidelines on the overall utilization of antihypertensive drug classes and within subgroups with compelling indications.

Results: A total of 29,901 adults were included. Following guidelines implementation, angiotensin receptor blockers (ARBs) utilization increased from 18% to 26% (adjusted OR [aOR] = 1.35; 95% confidence interval [CI]: 1.21-1.50, p < 0.0001), and calcium channel blocker (CCB) use increased from 28% to 32% (aOR = 1.24; 95% CI: 1.13-1.36, p < 0.0001). In contrast, fixed-dose combination (FDC) utilization declined from 22% to 16% (aOR = 0.67; 95% CI: 0.59-0.75, p < 0.0001). Utilization of other antihypertensive classes did not change significantly.

Conclusion: After the 2017 ACC/AHA guidelines update, antihypertensive prescribing in the US showed increased use of ARBs and CCBs. However, declining FDC use highlights a persistent gap between evidence-based guidance and real-world practice.

Introduction: Prosthetic Joint Infection (PJI) is a serious and potentially fatal consequence of total joint arthroplasty that is primarily due to the formation of bacterial biofilms on surgical orthopedic implants. Such orthopedic infections often face antibiotic resistance; therefore, novel antimicrobial substances are in demand to combat the biofilm-associated infections in orthopedic implants. This study investigated the potential of AgNPs-AMP conjugate coated implants in combating micro-organisms responsible for biofilm formation on orthopedic joint implants causing PJI.

Methods: Green synthesized AgNPs from leaf extracts were conjugated with the AMP extracted from the Bellamya bengalensis, which was characterized using UV Spectroscopy, zeta potential. The antibacterial activity of the AgNPs, AMP and AgNPs-AMP conjugate were assessed using the Well diffusion method. The effect of biofilm formation and inhibition of Staphylococcus aureus, and Staphylococcus epidermidis on the ½ MIC, 1X MIC, and 2X MIC were investigated using agar diffusion test. In addition, MTT assay was performed to determine the cytotoxic effects of AMP-AgNPs conjugate on the L929 cell line.

Results: The UV Vis spectroscopy and zeta potential confirmed the synthesis of AgNPs, as well as the conjugation of AMP with AgNPs. The AMP-AgNPs revealed their significant bactericidal potential against the S. aureus, and S. epidermidis, with the antibacterial testing. The quantitative and qualitative analysis of biofilm inhibition revealed that all the tested concentrations of AMP-AgNPs conjugate (½ MIC, 1X MIC, and 2X MIC) effectively inhibited the biofilm formation of S. aureus and S. epidermidis.

Discussion: It was concluded that the treatment of different concentrations of AMP-AgNPs did not influence the cell viability of the L929 cells. This study demonstrated that the AgNPs-AMP can be coated with orthopedic implants to prevent biofilm formation on orthopedic joint implants.

Female reproductive disorders represent a major global health challenge. Despite their clinical heterogeneity, these conditions share core pathological mechanisms including oxidative stress, chronic inflammation, hormonal imbalance, metabolic dysfunction, extracellular matrix remodeling, and dysregulated cell survival. Current therapies rarely target these interconnected processes, underscoring the need for multi-pathway modulators. Luteolin, a dietary flavone, has emerged as a promising candidate due to its regulatory effects on redox balance, NF-κB/MAPK signaling, PI3K/AKT/PTEN pathways, TGF-β/Smad-mediated fibrosis, and estrogen and progesterone receptor activity. Preclinical and mechanistic evidence demonstrates luteolin's benefits across major reproductive disorders. In PCOS, it improves insulin sensitivity, supports ovulatory function, modulates hepatic and ovarian gene expression, and influences gut microbiota. In endometriosis, it disrupts epithelial-macrophage crosstalk, reduces chemokine-driven inflammation, and inhibits angiogenesis and lesion growth. In leiomyomas, luteolin attenuates fibrosis and normalizes apoptotic and TGFB1/PI3K/PTEN signaling. Protective effects on ovarian reserve in primary ovarian insufficiency, anti-inflammatory and anti-ferroptotic actions in endometritis, and suppression of sFlt-1 and HIF-1α in preeclampsia further highlight its relevance to reproductive pathology. Anticancer and chemosensitizing effects have also been reported in ovarian, cervical, and endometrial cancers. Although clinical translation is constrained by poor solubility and bioavailability, emerging nanocarrier and prodrug strategies markedly improve luteolin's pharmacokinetic profile. Human studies of luteolin-based formulations support anti-inflammatory and antioxidant effects consistent with reproductive disease mechanisms. Overall, luteolin represents a multi-target pharmacological candidate with translational potential in gynecologic and endocrine disorders, warranting further optimization and early-phase clinical investigation.