European journal of pharmacology最新文献

{"title":"Corrigendum to \"Piezo1 activation mediates stiffness-induced aortic medial calcification: Pharmacological evidence from agonist and antagonist studies\" [Eur. J. Pharmacol. 1011 (2026) 178465].","authors":"Yuting Liu, Jingjing Guo, Xiaoying Gu, Jiawei Xu, Boyu Duan, Yuxin Miao, Lin Xiao, Hongmei Xue, Qi Guo, Danyang Tian, Sheng Jin, Yingqian Zhang, Yuming Wu, Xu Teng","doi":"10.1016/j.ejphar.2026.179083","DOIUrl":"10.1016/j.ejphar.2026.179083","url":null,"abstract":"","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"179083"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valsartan repurposing to mitigate autoimmune encephalomyelitis via ACE2/Ang1-7/MasR axis pathway cognitive and neuroinflammation modulation; an experimental and chem-bio-informatics study","authors":"Mostafa A. Rabie,&nbsp;Rania M. Rahmo,&nbsp;Hekmat M. El Magdoub,&nbsp;Nadia M. Hamdy,&nbsp;Lobna H. Khedr","doi":"10.1016/j.ejphar.2026.179146","DOIUrl":"10.1016/j.ejphar.2026.179146","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a debilitating neuroinflammatory disease frequently associated with cognitive impairment. Recent research suggests that targeting the renin-angiotensin system (RAS) may offer a promising therapeutic strategy for alleviating cognitive deficits in neurodegenerative disorders. This study aimed to explore the interactions between valsartan (VAL), an angiotensin II receptor antagonist, ACE2/Ang 1–7/MasR signaling, and PI3K/Akt/CREB/BDNF pathway in preserving cognitive function using an experimental autoimmune encephalomyelitis (EAE) mouse model. EAE was induced in mice through spinal cord homogenate, leading to motor and cognitive impairments that mimic those observed in MS patients. In addition, comprehensive bioinformatics and chemo-bioinformatics analyses were conducted.</div><div>Oral administration of VAL (40 mg/kg/day) significantly ameliorated EAE-induced cognitive deficit in spatial and learning memory as evidenced by improved performance in the novel object recognition (NOR) and Morris water maze (MWM), along with a reduction in EAE clinical scoring. Histological analysis further revealed that VAL treatment mitigated EAE-induced demyelination in the corpus callosum.</div><div>Mechanistically, VAL activated ACE2/Ang 1-7/MasR signaling pathway, stimulating the p-PI3K/p-Akt/p-CREB axis, and consequently elevating BDNF, its receptor TrkB and synapsin I, thereby establishing a cycle of neuroprotection. Furthermore, VAL mitigated EAE-induced neuroinflammation by reducing p-NFκB p65, TNF-α and IL-6 contents, while restoring redox balance by enhancing SOD and GPx activities, elevating GSH content and reducing MDA content. Collectively, these findings highlight the potential of VAL in preserving cognitive function in EAE by modulating key neuroprotective and anti-inflammatory pathways, offering valuable insights into novel therapeutic strategies for MS and related neuroinflammatory disorders. These conclusions are further supported by complementary bioinformatics analyses.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179146"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Casomorphins as opioid peptide modulators of tumor biology and immune signaling","authors":"Wojciech Kamysz,&nbsp;Krystian Małek,&nbsp;Patrycja Kleczkowska","doi":"10.1016/j.ejphar.2026.179082","DOIUrl":"10.1016/j.ejphar.2026.179082","url":null,"abstract":"<div><div>β-casomorphins (BCMs) are bioactive peptides generated from milk β-casein digestion, which interact with opioid and other receptors to affect both tumor cell proliferation and immune responses within the tumor microenvironment. This review is aimed at summarizing current evidence on the anti-proliferative and immunomodulatory activities of BCMs, in particular BCM-5 and BCM-7, and their relevance to cancer biology. Studies have shown that BCM-5 primarily inhibits cancer cell growth, whereas BCM-7, in addition, enhances anti-tumor immunity by promoting CD8⁺ T cell infiltration and reducing regulatory T cell populations. The review also discusses synthetic cyclic analogs designed to improve peptide stability and bioavailability, which demonstrate opioid-independent antiproliferative activities. By integration of mechanistic, <em>in vitro</em>, and <em>in vivo</em> data, this review emphasizes the potential of β-casomorphins and their derivatives as modulators of tumor progression and immune surveillance and identifies gaps in knowledge to guide future research in oncology.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179082"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of metformin on anti-Alzheimer activity of rivastigmine in aluminum chloride-induced Alzheimer's disease in rats: A behavioral, biochemical, immunohistopathological evidence of crosstalk between amyloid, tau, autophagy, and apoptosis","authors":"Raafat A. Abdel-Aal,&nbsp;Sara Abdelnabi,&nbsp;Dalia M. Badary,&nbsp;Abeer M.R. Hussein","doi":"10.1016/j.ejphar.2026.179087","DOIUrl":"10.1016/j.ejphar.2026.179087","url":null,"abstract":"<div><h3>Aim</h3><div>This study investigates how the anti-Alzheimer's effectiveness of rivastigmine (RIVA) is affected by the antidiabetic drug metformin (MET).</div></div><div><h3>Methodology</h3><div>Male rats were randomly divided into a control group, an Alzheimer's disease (AD) group receiving aluminum chloride (AlCl₃), a RIVA-treated group, a MET-treated group, and a RIVA + MET combination group. Cognitive performance was assessed using passive avoidance (PA), the radial arm maze (RAM), the Morris water maze (MWM), and novel object recognition (NOR) tests. Hippocampal microtubule-associated protein tau (MAPT), beta-site APP cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), and autophagy marker Sequestosome 1 (SQSTM1/p62) were measured, while amyloid-beta (Aβ) and caspase-3 expression were analyzed immunohistochemically. Histopathology and electron microscopy were used to assess neuronal integrity.</div></div><div><h3>Results</h3><div>MET, RIVA, and their combined treatment mitigated the neurodegenerative alterations induced by AlCl₃. The combination of MET + RIVA failed to yield significant differences in behavioral performance [PA, RAM, MWM, and NORT], MAPT levels, and AChE activity compared with the treatment with RIVA monotherapy. However, the combination therapy showed significant reductions in hippocampal BACE1, Aβ deposition, and SQSTM1/p62 levels, indicating enhanced suppression of amyloidogenic processing and improved autophagy. Although differences between MET + RIVA combination and RIVA monotherapy were not statistically significant for these markers, the combination markedly reduced caspase-3 immunoreactivity compared with the diseased group, indicating greater attenuation of apoptosis.</div></div><div><h3>Conclusion</h3><div>These results highlight the crosstalk among the amyloid, tau, autophagy, and apoptotic pathways in AD and suggest that the MET + RIVA combination showed promising molecular improvements but no clear behavioral superiority, indicating the need for further optimization.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179087"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico prediction of gallic acid binding to Zika virus NS3/RdRp proteins and in vitro confirmation of its antiviral activity","authors":"Jun-Ho Heo,&nbsp;Nalae Kang,&nbsp;Yeon-Ji Lee,&nbsp;Eun-A Kim,&nbsp;Soo-Jin Heo","doi":"10.1016/j.ejphar.2026.179088","DOIUrl":"10.1016/j.ejphar.2026.179088","url":null,"abstract":"<div><div>The global health threat posed by the Zika virus (ZIKV), characterized by its association with severe neurological sequelae and congenital malformations, is exacerbated by the current lack of clinically approved antiviral interventions. This study aimed to identify a benzoic acid–derived anti-ZIKV candidate through in silico–in vitro screening of derivatives and to characterize the selected lead compound. Gallic acid (GA), a naturally occurring phenolic compound, emerged as the most suitable candidate and was selected for further analyses. Molecular docking and 100 ns molecular dynamics (MD) simulations demonstrated that GA formed stable interactions with the catalytic domains of ZIKV NS3 and RdRp, with conformational perturbations in RdRp. This suggests that GA inhibits protein activation through active-site occlusion and/or structural destabilization. Treatment with non-cytotoxic concentrations of GA significantly suppressed viral replication in ZIKV-infected Vero E6 cells, with &gt;98% inhibition of plaque formation and NS1 mRNA expression at concentrations of 100–200 μM, and modulated the expression of innate immune response genes including TNF-α, IFIT, IFITM, OAS, and PKR. Collectively, these findings indicate that GA exerts potent antiviral activity through the direct inhibition of viral non-structural proteins, underscoring its potential as a promising lead compound for the development of anti-ZIKV therapeutics.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179088"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338332","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":"Repeated ethanol exposure in female rats impairs cerebral endothelial function and increases cerebrovascular stiffness","authors":"Emily J. Baumoel,&nbsp;Madison C. Heitkamp,&nbsp;Anduela Thaqi,&nbsp;Jared Luchetta,&nbsp;Gianna M. DeMarco,&nbsp;Anushree N. Karkhanis,&nbsp;Abbie C. Chapman","doi":"10.1016/j.ejphar.2026.179104","DOIUrl":"10.1016/j.ejphar.2026.179104","url":null,"abstract":"<div><div>There are several lifestyle factors known to increase the risk for age-related cognitive decline and dementia, including chronic alcohol consumption and alcohol use disorder. Chronic alcohol use in adulthood causes decreased gray matter and atrophy in brain regions central to learning and memory, including the hippocampus. Further, people with alcohol use disorder have a high incidence of cerebral white matter hyperintensities, the hallmark of cerebral small vessel disease, suggesting a link between alcohol consumption and cerebrovascular disease. However, how ethanol exposure impacts the cerebral circulation remains unclear. Here, we investigated the effects of a single ethanol vapor exposure (12 h), repeated ethanol exposures (12 h/day for 10 days) or air exposure (controls; n = 8/group) on cerebrovascular function and structure in adult female Wistar rats, as women are more sensitive to alcohol-related brain injury. Endothelial function and myogenic reactivity of isolated and pressurized posterior cerebral arteries (PCAs), the pial artery responsible for perfusing the hippocampus, were assessed ex-vivo using pressure myography. Both single and repeated ethanol exposure impaired PCA endothelial function, however, had a differential effect on myogenic tone. Repeated ethanol exposure caused oxidative stress, vascular inflammation and reduced myogenic tone of PCAs compared to a single exposure. Further, PCAs from rats repeatedly exposed to ethanol were stiffer than arteries from controls and a single ethanol exposure, which commonly occurs with aging. These findings demonstrate that ethanol exposure rapidly impairs endothelial function in the cerebrovasculature of females and suggest that repeated exposures may result in disrupted hemodynamics and accelerated vascular aging.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179104"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367621","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":"Longifolene mitigates amyloid beta induced neurotoxicity by acting on PI3K/AKT/NFκB pathway: Comprehensive in vitro, in vivo pharmacokinetics and pharmacodynamic studies for Alzheimer's disease","authors":"Ami Thakkar,&nbsp;Chandrashekhar Mote,&nbsp;Amruta Gadade,&nbsp;Vikas Dighe,&nbsp;Ginpreet Kaur,&nbsp;Amisha Vora","doi":"10.1016/j.ejphar.2026.179119","DOIUrl":"10.1016/j.ejphar.2026.179119","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a multifactorial disease characterized with deposition of Amyloid-β peptide leading to oxidative stress and neuroinflammation. Terpenes are a broad class of natural compounds known to possess anti-oxidant and anti-inflammatory effects. Longifolene (LNF), a major constituent of pine resin is a non -polar sesquiterpene possessing promising anti-oxidant and anti-inflammatory activity. Oxidative stress and neuroinflammation are pathological drivers of AD. The current work is focused on evaluating the neuroprotective potential of LNF using <em>in vitro</em> cell line-based and <em>in vivo</em> animal-based model for AD. Pre-treatment with LNF at 1, 10 and 100 μM displayed significant neuroprotective potential in Aβ_1-42 induced neurotoxicity in SH-SY5Y cell-line. Additionally, 0.5 and 1 μM of LNF significantly prevented ROS generation, mitochondrial dysfunction and apoptosis in SH-SY5Y cell-line. Pharmacokinetic studies in rats showed that LNF achieved the therapeutic concentrations in brain. Further, in pharmacodynamic studies, 20 days pre-treatment and 30 days post-treatment with LNF at 10, 50 and 100 mg/kg resulted in dose-dependent improvements in behavioral, biochemical and histopathological parameters in Aβ_1-42 induced AD in rats. Functional assays demonstrated that LNF brought about significant reduction in levels of AChE, TNF-α and IL-6 levels and elevation in BDNF in the rat brain. Histopathological examination of the cortex and hippocampus showed that LNF at doses of 50 and 100 mg/kg markedly attenuated neuronal swelling and cortical atrophic changes, while preserving the pyramidal layer thickness in the hippocampus. Protein expression studies using Western blot analysis showed that LNF displays anti-AD activity by acting on PI3K/AKT/NFκB pathway. These findings highlight LNF as a potential neuroprotective agent for AD intervention.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179119"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSC-derived exosomes delivery of miR-714 protect mouse BV2 microglial cells from OGD/R injury by directly targeting ITGAM","authors":"Xiao-xia Yang,&nbsp;Yong-jie Wang,&nbsp;Ai-ying Xue,&nbsp;Xia Xue,&nbsp;De-qing Sun","doi":"10.1016/j.ejphar.2026.179148","DOIUrl":"10.1016/j.ejphar.2026.179148","url":null,"abstract":"<div><div>MicroRNAs have been widely demonstrated to participate in the pathogenesis of cerebrovascular diseases. In this study, an <em>in vitro</em> cellular oxygen-glucose deprivation/reoxygenation (OGD/R) model was established in mouse BV2 microglial cells, and differentially expressed microRNAs (DEMs) were screened by small RNA sequencing. The significant downregulation of miR-714 during OGD/R process was confirmed and its effects was verified by CCK-8 and apoptosis assays. MSC-derived exosomes (MSC-exo) were used to transport miR-714, and the mRNA expression level and cellular uptake of miR-714 were detected by qRT-PCR and fluorescence microscopy, respectively. The effects of MSC-exo-miR-714 on the proliferation and apoptosis of OGD/R BV2 cells were evaluated by CCK-8, Annexin V-FITC/PI double staining and TUNEL assays. In addition, bioinformatics analysis was performed to predict the target genes of miR-714. qRT-PCR and Western blotting were used to verify the regulatory effects of MSC-exo-miR-714 on ITGAM (integrin subunit alpha M) at mRNA and protein levels. The potential anti-inflammatory mechanism was further explored using gene enrichment analysis and Western blotting. The results showed that MSC-exo-miR-714 could significantly promote proliferation, inhibit apoptosis, and reduce protein expression of IL-6, IL-1β, TNF-α, NF-κB, and p-NF-κB in OGD/R-injured BV2 cells by directly targeting ITGAM. In conclusion, miR-714 is significantly down-regulated under <em>in vitro</em> OGD/R injury and serves as a key regulator in BV2 microglial injury. MSC-exo-miR-714 protects glial cells against OGD/R damage <em>in vitro</em> by directly targeting ITGAM and inhibiting inflammatory signaling. These findings are limited to the <em>in vitro</em> setting, and further <em>in vivo</em> validation is required.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179148"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peimisine ameliorates allergic asthma by suppressing Th2-associated inflammation and oxidative stress","authors":"Shu-Chen Cheng,&nbsp;Chian-Jiun Liou,&nbsp;Yun-Yi Guo,&nbsp;Po-Ting Lin,&nbsp;Wen-Chung Huang","doi":"10.1016/j.ejphar.2026.179085","DOIUrl":"10.1016/j.ejphar.2026.179085","url":null,"abstract":"<div><div><em>Fritillaria thunbergii</em> Miq. has been traditionally used to treat respiratory disorders in Chinese medicine. Peimisine, a major <em>F. thunbergii</em> alkaloid, has anti-inflammatory and antioxidant effects, but its role in allergic asthma and mucus-driven airway remodeling remains unclear.</div><div>This study investigated whether peimisine could attenuate asthmatic phenotypes and explored its mechanistic links to Th2 inflammation, epithelial activation, and oxidative stress. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) and treated with peimisine. Airway hyperresponsiveness (AHR) and lung function were measured, and lung tissues were evaluated for inflammatory infiltration, goblet cell hyperplasia/mucus hypersecretion, and remodeling. Inflammatory mediators and oxidative stress indices were determined in bronchoalveolar lavage fluid (BALF) and lung homogenates. In vitro, BEAS-2B bronchial epithelial cells were used to assess inflammatory activation, intracellular reactive oxygen species (ROS) generation, and monocyte–epithelial adhesion. Peimisine significantly improved AHR and reduced airway inflammatory cell infiltration. It also suppressed goblet cell expansion, mucus hypersecretion, and collagen deposition. Mechanistically, peimisine attenuated Th2-skewed inflammation, reducing BALF eosinophils, Th2 cytokines, eotaxins, and OVA-specific IgE/IgG1 while increasing Th1-associated markers and OVA-specific IgG2a. Peimisine restored redox balance and inhibited NF-κB activation in lung tissue. Consistently, peimisine downregulated epithelial eotaxins, ICAM-1, and pro-inflammatory cytokines in BEAS-2B cells, concomitant with reduced ROS production and diminished monocyte adhesion. Overall, peimisine alleviated allergic asthma by reducing airway inflammation and oxidative stress and by limiting Th2 immune activation, thereby decreasing epithelial inflammatory responses, mucus hypersecretion, and airway remodeling. These results suggest that peimisine may be a promising therapeutic candidate for allergic asthma.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179085"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148316369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of phytochemicals on statin efficacy and safety: A review","authors":"Pooya Vatankhah,&nbsp;Vahab Alamdari-Palangi,&nbsp;Mehdi Kian,&nbsp;Fatemeh Hosseinpour-Soleimani,&nbsp;Amir Savardshtaki,&nbsp;Amir Tajbakhsh,&nbsp;Mohammad Hashem Hashempur","doi":"10.1016/j.ejphar.2026.179129","DOIUrl":"10.1016/j.ejphar.2026.179129","url":null,"abstract":"<div><div>Statins are widely prescribed lipid-lowering agents but are associated with adverse effects such as myopathy and, less commonly, cognitive disturbances. Increasing evidence suggests that plant-derived phytochemicals can interact with statins, producing both beneficial and potentially harmful effects. Preclinical and limited clinical evidence suggests that selected phytochemicals may enhance certain therapeutic effects of statins and may contribute to adverse effect mitigation; however, their potential to support statin dose reduction requires confirmation in well-designed clinical trials. Phytochemicals may reduce inflammation and oxidative stress, potentially enabling lower statin doses. By elucidating these interactions, healthcare providers can develop personalized treatment strategies that enhance therapeutic outcomes of statins while minimizing risks. This review aims to clarify the intricate relationship between specific phytochemicals and statins, emphasizing the need for further investigation into their combined effects on cardiovascular health. The strength of evidence varies considerably across the available literature, ranging from randomized controlled trials to preclinical <em>in vitro</em> and animal studies. Consequently, the translational applicability of many reported phytochemical–statin interactions remains uncertain and warrants further clinical investigation. In addition to potentially beneficial effects, several phytochemicals may pose clinically relevant safety concerns through mechanisms, such as CYP3A4 inhibition, leading to increased statin exposure and toxicity; OATP inhibition, potentially reducing hepatic statin uptake and therapeutic efficacy; and hERG channel blockade, which may increase the risk of QT prolongation. These interactions may contribute to adverse outcomes, including statin-associated myopathy and, in rare cases, rhabdomyolysis.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1030 ","pages":"Article 179129"},"PeriodicalIF":5.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}