Biomedicine & Pharmacotherapy最新文献

{"title":"Sodium-glucose co-transporters (SGLT2) inhibitors prevent lipid droplets formation in vascular inflammation or lipid overload by SGLT2-independent mechanism","authors":"Natalia Chorazy ,&nbsp;Kamila Wojnar-Lason ,&nbsp;Anna M. Gdula ,&nbsp;Diane Bakker ,&nbsp;Coert J. Zuurbier ,&nbsp;Stefan Chlopicki ,&nbsp;Marta Z. Pacia","doi":"10.1016/j.biopha.2025.117967","DOIUrl":"10.1016/j.biopha.2025.117967","url":null,"abstract":"<div><h3>Background</h3><div>The formation of vascular lipid droplets (LDs) induced by vascular inflammation or lipid overload contributes to vascular pathophysiology in diabetes and cardiometabolic diseases, while sodium-glucose co-transporter 2 inhibitors (SGLT2-I) are beneficial in treating these conditions. Thus, we hypothesized that SGLT2-I would directly modify vascular LDs formation during vascular inflammation or lipid overload, and explored underlying mechanisms.</div></div><div><h3>Methods</h3><div>LDs formation in isolated murine aorta from wild-type or SGLT2-KO animals was induced by either treatment with tumour necrosis factor (TNF) to induce vascular inflammation or using oleic acid (OA) to mimic lipid overload. Vascular LDs and markers of vascular inflammation were monitored through fluorescence microscopy. Pharmacological inhibitors of sodium-hydrogen exchanger 1 (NHE1), endothelial sodium channels (EnNaC), sodium-calcium exchanger (NCX), protein kinase C (PKC), and NOX1/4 were used to test their role in empagliflozin’s effects on vascular LDs.</div></div><div><h3>Results</h3><div>Empagliflozin, dapagliflozin or ertugliflozin inhibited LDs formation in aorta exposed to TNF or OA. Empagliflozin reduced vascular inflammation (based on ICAM-1) and TNF/OA-induced LDs formation. These effects persisted in SGLT2-KO mice. Inhibition of NHE1, PKC or NOX1/4 recapitulated empagliflozin’s effects on TNF-induced vascular inflammation, without additional effects of empagliflozin. However, NHE1 inhibition was not involved in the SGLT2-independent reduction of OA-induced LDs formation by empagliflozin.</div></div><div><h3>Conclusions</h3><div>This is the first report demonstrating that SGLT2-I prevent the formation of LDs in the vasculature. Empagliflozin downregulates LDs formation in vascular inflammation or lipid overload <em>via</em> an SGLT2-independent mechanism. Empagliflozin’s protective effects involve the NHE1/PKC/NOX pathway in the TNF response but not in the OA response.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117967"},"PeriodicalIF":6.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of keratinocyte proliferation and differentiation by secoiridoid oleacein in monoculture and fibroblast co-culture models","authors":"Juhee Cho ,&nbsp;Meriem Bejaoui ,&nbsp;Hiroko Isoda","doi":"10.1016/j.biopha.2025.117985","DOIUrl":"10.1016/j.biopha.2025.117985","url":null,"abstract":"<div><div>Aberrant differentiation of keratinocytes is closely associated with both pathological skin disorders and non-pathological skin conditions, making the maintenance of normal differentiation process essential for skin integrity and homeostasis. This study investigated the effect of olive-derived secoiridoid oleacein (OC) on keratinocyte proliferation and differentiation <em>in vitro</em> and further validated it in a co-culture model with fibroblasts mimicking a skin-like environment. OC was compared with oleuropein (OP) as a reference compound having similar chemical structure and reported effects on skin barrier formation and wound healing. Notably, OC significantly increased the proliferation makers <em>KRT5</em> and <em>KRT14</em> and demonstrated wound healing effect under low-calcium condition, reflecting characteristics of the basal layer. Under high-calcium condition, OC markedly upregulated differentiation markers <em>KRT10</em>, <em>IVL</em>, <em>FLG</em>, and <em>TGM1</em>, along with differentiation characteristics such as cytoplasmic extensions and cell adhesion. Transcriptomic analysis revealed that OP and OC shared a common upstream pathway, Integrin/E-cadherin-Rho-MAPK, at the cytoplasm, while they showed distinct regulatory mechanisms within the nucleus. OP induced differentiation by suppressing stemness genes through epigenetic regulation, whereas OC secured differentiation stability by suppressing proliferative gene <em>ESR1</em> and activating the DNA damage response from DNA damage or mechanical stress occurring during differentiation. Our study is the first to elucidate the dual regulatory effects of OC on keratinocyte proliferation and differentiation stage-dependently as well as its underlying molecular mechanisms, suggesting that the divergent regulatory mechanisms may be due to their structural differences. These findings highlight OC as a skin protective agent for maintaining skin health and suggest its therapeutic potential for skin disorders related to abnormal differentiation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117985"},"PeriodicalIF":6.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “A novel missense mutation Smad4 V354L enhances the efficacy of docetaxel in non-small cell lung cancer” [Biomed. Pharmacother. 184 (2025) 117899]","authors":"Xia Xue ,&nbsp;Yongjia Zhou ,&nbsp;Huiping Liu ,&nbsp;Yan Gao ,&nbsp;Xinyu Ma ,&nbsp;Zhaohua Xiao ,&nbsp;Wenhao Zhang ,&nbsp;Peichao Li ,&nbsp;Zhongxian Tian ,&nbsp;Yun Luan ,&nbsp;Xiaogang Zhao","doi":"10.1016/j.biopha.2025.117970","DOIUrl":"10.1016/j.biopha.2025.117970","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117970"},"PeriodicalIF":6.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the mechanisms of PARP inhibitor resistance in prostate cancer: Implications for precision medicine","authors":"Cheng Wang ,&nbsp;Xiaoran Han ,&nbsp;Shaoqiu Kong ,&nbsp;Shanhua Zhang ,&nbsp;Hao Ning ,&nbsp;Fei Wu","doi":"10.1016/j.biopha.2025.117955","DOIUrl":"10.1016/j.biopha.2025.117955","url":null,"abstract":"<div><div>Prostate cancer is a leading malignancy among men. While early-stage prostate cancer can be effectively managed, metastatic prostate cancer remains incurable, with a median survival of 3–5 years. The primary treatment for advanced prostate cancer is androgen deprivation therapy (ADT), but resistance to ADT often leads to castrationresistant prostate cancer (CRPC), presenting a significant therapeutic challenge. The advent of precision medicine has introduced promising new treatments, including PARP inhibitors (PARPi), which target defects in DNA repair mechanisms in cancer cells. PARPi have shown efficacy in treating advanced prostate cancer, especially in patients with metastatic CRPC (mCRPC) harboring homologous recombination (HR)-associated gene mutations. Despite these advancements, resistance to PARPi remains a critical issue. Here, we explored the primary mechanisms of PARPi resistance in prostate cancer. Key resistance mechanisms include homologous recombination recovery through reverse mutations in BRCA genes, BRCA promoter demethylation, and non-degradation of mutated BRCA proteins. The tumor microenvironment and overactivation of the base excision repair pathway also play significant roles in bypassing PARPi-induced synthetic lethality. In addition, we explored the clinical implications and therapeutic strategies to overcome resistance,emphasizing the need for precision medicine approaches. Our findings highlight the need for comprehensive strategies to improve PARPi sensitivity and effectiveness,ultimately aiming to extend patient survival and improve the quality of life for those with advanced prostate cancer. As our understanding of PARPi resistance evolves, more diverse and effective individualized treatment regimens will emerge.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117955"},"PeriodicalIF":6.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mineralocorticoid receptor antagonism improves corneal integrity in a rat model of limbal stem cell deficiency","authors":"Daniela Rodrigues-Braz ,&nbsp;Clémence Bonnet ,&nbsp;Linxin Zhu ,&nbsp;Nilufer Yesilirmak ,&nbsp;Emmanuelle Gélizé ,&nbsp;Laurent Jonet ,&nbsp;Frédéric Jaisser ,&nbsp;Jean-Louis Bourges ,&nbsp;Francine Behar-Cohen ,&nbsp;Min Zhao","doi":"10.1016/j.biopha.2025.117979","DOIUrl":"10.1016/j.biopha.2025.117979","url":null,"abstract":"<div><div>Limbal stem cell deficiency (LSCD) is a sight-threatening condition caused by the loss and/or dysfunction of limbal stem cells (LSCs), which are essential for corneal epithelial regeneration and homeostasis and are critical for maintaining corneal transparency. We have previously shown that specific inactivation of the endothelial mineralocorticoid receptor (MR) inhibits corneal neovascularization (CN) and that MR antagonists (MRA) improve corneal epithelial wound healing. This study investigated the therapeutic potential of MRA in LSCD and their mechanisms of action. Using a rat model of LSCD, systemic administration of spironolactone (SPL) or a more specific MRA, eplerenone, similarly reduced CN and corneal oedema, demonstrating MR-specific effects. SPL further limited inflammation, enhanced the corneal epithelial barrier, reduced corneal conjunctivalization and promoted nerve regeneration, highlighting its potential to improve corneal integrity. Transcriptomic analysis revealed that SPL upregulated genes associated with LSC maintenance (<em>Tp63</em>, <em>Wnt6</em>), corneal epithelial differentiation (<em>Vdr</em>, <em>Fermt1</em>, <em>Ehf</em>) and nerve regeneration (<em>Sprr1a</em>, <em>Anxa1</em>), while downregulating genes associated with angiogenesis (<em>Kdr</em>, <em>Scube2</em>), inflammation (<em>Ccl2</em>, <em>Cxcl1</em>) and fibrosis (<em>Fbln1</em>, <em>Snai1</em>). Conversely, transgenic rats overexpressing human <em>NR3C2</em> encoding MR showed corneal epithelial irregularities and dysregulation of genes related to extracellular matrix remodeling and fibrosis (<em>Matn3</em>, <em>Serpine2</em>, <em>Fmod</em>, <em>Bgn</em>, <em>Ddr2</em>), angiogenesis (<em>Nrp2</em>, <em>Scube1</em>) and limbal cell function (<em>Ifitm3</em>). These findings demonstrate that activation of the MR pathway disrupts limbal and corneal homeostasis and that SPL effectively modulates critical mechanisms in LSCD, offering promising therapeutic potential to reduce CN and improve corneal epithelial barrier integrity.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117979"},"PeriodicalIF":6.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streptococcus thermophilus CNCM I-5570 lysate counteracts the aging process in human dermal fibroblast cells by neutralizing harmful free radicals and impacting antioxidant and anti-inflammatory pathways, thus restoring their physiological functions","authors":"Francesca Rosaria Augello ,&nbsp;Francesca Lombardi ,&nbsp;Alessia Ciafarone ,&nbsp;Serena Altamura ,&nbsp;Massimiliano Marazzato ,&nbsp;Serena Artone ,&nbsp;Benedetta Cinque ,&nbsp;Paola Palumbo","doi":"10.1016/j.biopha.2025.117975","DOIUrl":"10.1016/j.biopha.2025.117975","url":null,"abstract":"<div><div>Previous studies have highlighted the <em>in vitro</em> and <em>in vivo</em> anti-aging potential of <em>Streptococcus thermophilus</em> prompting us to investigate the biomolecular mechanisms underlying its effects. We evaluated the reparative ability of <em>S. thermophilus</em> lysate in a hydrogen peroxide (H₂O₂)-induced senescence model of human dermal fibroblasts (HDFs). Cell proliferation, cell number, and senescence level were evaluated by IncuCyte® Live Cell Imager system, trypan blue dye exclusion test and β-galactosidase activity, respectively. We analyzed p21, prolyl 4-hydroxylase A1, intracellular collagen I, nuclear factor E2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB) and heme oxygenase-1 expression through western blot. Extracellular levels of collagen I, interleukin-1β, and IL-6 were assessed by ELISA. The oxidative stress markers were assayed using standard methods. The direct antioxidant activity of probiotic was quantified using multiple techniques. The presence of antioxidant genes in probiotic was detected via PCR assay. Probiotic lysate exposure increased the proliferation rate, counteracted the aging by reducing β-galactosidase activity and p21 levels, promoted collagen I synthesis and neutralized oxidative stress by activating Nrf2. The probiotic lysate inhibited the NF-κB pathway with pro-inflammatory marker downregulation. Notably, we revealed that probiotic exhibited strong free radical scavenging ability, iron-chelating properties, and significant ferric reducing power in a concentration-dependent manner. We identified seven genes with antioxidant function in its genome. Our results show that <em>S. thermophilus</em> lysate is efficacious in suppressing the biomolecular events associated with H₂O₂-induced cellular aging, thus supporting the reparative action of <em>S. thermophilus</em>, helpful in treating skin aging.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117975"},"PeriodicalIF":6.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of protein glycation by vasodilatory β-blockers – In vitro studies and in silico analyses","authors":"Szymon Drygała ,&nbsp;Małgorzata Żendzian-Piotrowska ,&nbsp;Michał Radzikowski ,&nbsp;Anna Zalewska ,&nbsp;Mateusz Maciejczyk","doi":"10.1016/j.biopha.2025.117976","DOIUrl":"10.1016/j.biopha.2025.117976","url":null,"abstract":"<div><div>Glycation is defined as a non-enzymatic reaction wherein reducing sugars interact with amino acid residues present in proteins, resulting in the formation of advanced glycation end-products (AGE). This biochemical phenomenon is linked to several pathological conditions, particularly cardiovascular disease (CVD) and diabetes, as it significantly contributes to the onset of endothelial dysfunction and inflammation. Given these connections, vasodilatory β-blockers (VBB) have garnered interest due to their multifaceted pharmacological effects that extend beyond traditional β-adrenergic blockade. These agents not only enhance endothelial function but also exhibit notable antioxidant and anti-inflammatory properties, which may be associated with their capacity to inhibit glycation processes. In our study, we examined these properties through an in vitro and in silico study utilizing bovine serum albumin (BSA) as a model with multiple carbohydrates and aldehydes as glycation agents. Furthermore, we evaluated the binding affinity of VBB to BSA and pro-inflammatory proteins via molecular docking. The results indicated that while VBB were effective in diminishing the rates of protein glycation their effectiveness was generally lower than that of aminoguanidine, a recognized anti-glycation agent. In contrast, molecular docking analyses suggested that the anti-inflammatory properties of VBB may be due to their competition with glycation agents for binding sites on BSA, as well as their interactions with proteins integral to the activation of pro-inflammatory signaling pathways.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117976"},"PeriodicalIF":6.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organelle interplay in cardiovascular diseases: Mechanisms, pathogenesis, and therapeutic perspectives","authors":"Han Wu ,&nbsp;Hongtao Diao ,&nbsp;Feng Zhang,&nbsp;Weitao Jiang,&nbsp;Tengfei Pan,&nbsp;Yu Bian","doi":"10.1016/j.biopha.2025.117978","DOIUrl":"10.1016/j.biopha.2025.117978","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) are the leading cause of rising morbidity and mortality among humans worldwide; however, our approach to the pathogenesis, exploration, and management of CVDs still remains limited. As the heart consists of cardiomyocytes, cardiac fibroblasts, endothelial cells, smooth muscle cells, and several types of cells, different types of dysfunction in the interplay between organelles play an important damaging role, resulting in cardiac pathologies. The interplay between cellular organelles is intricate and vital for maintaining cellular homeostasis, as highlighted by multiple diseases linked to the dysfunction of both organelles. Many studies have revealed the potential mechanisms by which organelles communicate with each other and regulate the pathological processes of CVDs together. However, gaps remain in fully understanding the complexity of these interactions and translating these insights into therapeutic approaches. In this review, we summarized how the interplay between cellular organelles in the cardiomyocytes alters in various heart diseases. We find underexplored areas, such as the crucial signaling pathways governing organelle communication, and discuss their implications for disease future progression. Furthermore, we evaluate emerging potential medicines aimed at restoring organelle interactions. Finally, we propose future directions for researching to advance the development of novel medicines and therapies, addressing current gaps and providing a theoretical basis for improved clinical outcomes in CVDs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117978"},"PeriodicalIF":6.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive ocular delivery of adalimumab-loaded nanostructured lipid carriers for targeted retinitis pigmentosa therapy","authors":"Sheyla Velasco ,&nbsp;Idoia Gallego ,&nbsp;Lorena Olivares-González ,&nbsp;Gustavo Puras ,&nbsp;Ma Carmen Castro ,&nbsp;David Salom ,&nbsp;José Luis Pedraz ,&nbsp;Regina Rodrigo","doi":"10.1016/j.biopha.2025.117962","DOIUrl":"10.1016/j.biopha.2025.117962","url":null,"abstract":"<div><div>Retinitis pigmentosa is a genetically heterogeneous retinal degeneration process. There is hardly any treatment available. It is associated with extensive chronic inflammation and the release of proinflammatory cytokines such as TNFα. The blockade of TNFα through systemic or intraocular routes slows retinal degeneration. They are invasive routes with possible side effects. Herein, we propose a noninvasive approach to address the inflammatory component of retinitis pigmentosa. This approach is based on the development of eye drops of nanostructured lipid carriers (NLCs) loaded with the monoclonal antibody against TNFα, adalimumab (ADA). We physicochemically characterized NLC–ADA. We evaluated retinal and corneal toxicity; corneal permeation; diffusion to the retina; and effects on retinal dysfunction, degeneration and inflammation. These results prove that NLC–ADA eye drops exhibit excellent corneal permeation, no toxicity and high retinal distribution in mice. These compounds improve retinal function, reduce retinal degeneration and ameliorate the inflammatory process. In particular, NLC–ADA eye drops reduce M1 microglial activation, macrophage infiltration and the levels of some components of the NLRP3 inflammasome in <em>rd10</em> mice, a model of retinitis pigmentosa. This strategy offers a noninvasive route that circumvents the blood<img>retinal barrier in a safe and efficient manner. Hence, this approach could offer a promising therapeutic option for treating retinitis pigmentosa regardless of genetic defects. This approach could be useful for other inflammation-related retinal diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117962"},"PeriodicalIF":6.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Ibuprofen on glycerophospholipids and sphingolipids in context of Alzheimer´s Disease","authors":"Juliane Radermacher ,&nbsp;Vincent Konrad Johannes Erhardt ,&nbsp;Oliver Walzer ,&nbsp;Elodie Christiane Haas ,&nbsp;Konstantin Nicolas Kuppler ,&nbsp;Jill Sven René Zügner ,&nbsp;Anna Andrea Lauer ,&nbsp;Tobias Hartmann ,&nbsp;Heike Sabine Grimm ,&nbsp;Marcus Otto Walter Grimm","doi":"10.1016/j.biopha.2025.117969","DOIUrl":"10.1016/j.biopha.2025.117969","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a multifactorial disorder associated with neuroinflammation, elevated oxidative stress, lipid alterations as well as amyloid-deposits and the formation of neurofibrillary tangles. Ibuprofen, a globally used analgesic, is discussed to influence disease progression due to its anti-inflammatory effect. However, changes in lipid-homeostasis induced by Ibuprofen have not yet been analyzed. Here we investigate the effect of Ibuprofen on lipid classes known to be associated with AD. Ibuprofen treatment leads to a significant increase in phosphatidylcholine, sphingomyelin and triacylglyceride (TAG) species whereas plasmalogens, which are highly susceptible for oxidation, were significantly decreased. The observed alterations in phosphatidylcholine and sphingomyelin levels in presence of Ibuprofen might counteract the reduced phosphatidylcholine- and sphingomyelin-levels found in AD brain tissue with potential positive aspects on synaptic plasticity and ceramide-induced apoptotic effects. On the other hand, Ibuprofen leads to elevated TAG-level resulting in the formation of lipid droplets which are associated with neuroinflammation. Reduction of plasmalogen-levels might accelerate decreased plasmalogen-levels found in AD brains. Treatment of Ibuprofen in terms of lipid-homeostasis reveals both potentially positive and negative changes relevant to AD. Therefore, understanding the influence of Ibuprofen on lipid-homeostasis may help to understand the heterogeneous results of studies treating AD with Ibuprofen.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117969"},"PeriodicalIF":6.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}