Biomedicine & Pharmacotherapy最新文献

{"title":"Zolpidem suppresses cortical spreading depolarization and protects against ischemia/reperfusion injury and resulting neurological dysfunctions","authors":"Bartosz Pomierny ,&nbsp;Mateusz W. Kucharczyk ,&nbsp;Weronika Krzyżanowska ,&nbsp;Alicja Skórkowska ,&nbsp;Jakub Jurczyk ,&nbsp;Ewa Niedzielska-Andres ,&nbsp;Katarzyna Szafrańska ,&nbsp;Małgorzata Wolak ,&nbsp;Maria Walczak ,&nbsp;Maciej Gawlik ,&nbsp;Małgorzata Szafarz ,&nbsp;Katarzyna Przejczowska-Pomierny ,&nbsp;Elżbieta Wyska ,&nbsp;Marcin Kolaczkowski ,&nbsp;Lucyna Pomierny-Chamioło ,&nbsp;Monika Marcinkowska","doi":"10.1016/j.biopha.2025.118320","DOIUrl":"10.1016/j.biopha.2025.118320","url":null,"abstract":"<div><div>Building on clinical reports of symptomatic improvement in stroke patients following zolpidem administration, we investigated its neuroprotective efficacy and underlying mechanisms in a preclinical model of ischemia/reperfusion (I/R) injury. Pharmacokinetic analyses revealed that zolpidem preferentially accumulates in the hypothalamus and frontal cortex, with a notably prolonged half-life in the hypothalamus, suggesting region-specific drug retention. Early post-reperfusion administration of zolpidem (within 1.5 h) significantly reduced infarct volume, lowered glutamate levels, and improved motor recovery, underscoring a critical therapeutic window for intervention. Mechanistically, zolpidem enhanced phasic GABAergic signaling via α1 GABA-A receptors, reduced NKCC1 mRNA expression, and maintained neurochemical homeostasis without altering GABA transporter or receptor protein levels. Notably, zolpidem suppressed the frequency of cortical spreading depolarizations (CSDs), key propagators of secondary neuronal injury, without affecting wave dynamics, and modulated neurovascular coupling. Ischemic stroke outcomes are worsened by CSDs – waves of neuronal depolarization that propagate through compromised brain tissue and exacerbate secondary damage. These findings position zolpidem as a promising candidate for drug repurposing in stroke, uniquely targeting both early neuroprotection and longer-term functional recovery through selective modulation of GABAergic signaling and CSD suppression. Future clinical trials are warranted to define optimal therapeutic timing and maximize clinical benefit.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118320"},"PeriodicalIF":6.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting enhancer of zeste homolog 2: A novel therapeutic approach for head and neck cancer","authors":"Sarah Adriana Scuderi ,&nbsp;Laura Cucinotta ,&nbsp;Rossella Basilotta ,&nbsp;Deborah Mannino ,&nbsp;Nicoletta Palermo ,&nbsp;Emanuela Esposito ,&nbsp;Michela Campolo","doi":"10.1016/j.biopha.2025.118311","DOIUrl":"10.1016/j.biopha.2025.118311","url":null,"abstract":"<div><div>Head and neck cancer represents a diverse group of malignancies primarily affecting the oral cavity, pharynx, and larynx. Understanding the molecular mechanisms underlying head and neck cancer progression is crucial for developing targeted therapies. In the last years, great attention has been given to the role of Enhancer of Zeste Homolog 2 (EZH2), a key component of the Polycomb Repressive Complex 2 (PRC2), in cancer. EZH2 regulates critical pathways involved in cell proliferation, differentiation, and survival, which can contribute to the tumor microenvironment's dynamics. EZH2 overexpression has been implicated in the progression and metastasis of various cancers, including head and neck cancer, suggesting it could be used as a potential biomarker. EZH2 inhibitors are being explored in preclinical and clinical settings, aiming to enhance the efficacy of existing treatments. Understanding the role of EZH2 in head and neck cancer not only provides insights into the disease's biology but also paves the way for innovative therapeutic strategies that could improve patient outcomes. Thus, our review aims to deeply investigate the function of EZH2 in the pathological context of head and neck cancer, focusing on its potential as a molecular target for emerging therapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118311"},"PeriodicalIF":6.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of estrogens and steroid sulfatase inhibition in platinum resistance, proliferation, migration, and cell death in high-grade serous ovarian cancer cells","authors":"Nika Marolt ,&nbsp;Barry V.L. Potter ,&nbsp;Tea Lanišnik Rižner","doi":"10.1016/j.biopha.2025.118278","DOIUrl":"10.1016/j.biopha.2025.118278","url":null,"abstract":"<div><div>The high mortality rate associated with chemoresistance in high-grade serous ovarian cancer (HGSOC) underscores the urgent need for effective treatment strategies. This study explores the role of estrogens in six HGSOC cell lines differing in carboplatin sensitivity, estrogen receptor expression, and the ability to convert estrone sulfate (E1S) into active estrogens. We assessed the effects of the steroid sulfatase (STS) inhibitor STX64 and the estrogen agonists equilin (EQ) and ethinylestradiol (EE2) on cell viability, cell death and migration, as well as their interaction with carboplatin. STX64 IC₅₀ values for cell viability varied widely—from 18.21 µM (COV362) to over 90 µM in most lines. Significant viability reductions generally occurred at ≥ 50 µM, except in Kuramochi cells that were sensitive at 10 µM, and in OVSAHO and OVCAR-4 that responded at ≥ 0.01 µM. At higher concentrations, STX64 reduced viability in all cell lines, including ERα-negative cells. Combination treatment outcomes varied: STX64 reduced carboplatin efficacy in OVSAHO and COV362 but enhanced it in Caov-3. EQ and EE2 decreased viability in several cell lines, except in OVSAHO, where EQ promoted proliferation. Both enhanced the antimigratory effects of carboplatin in cell lines with moderate <em>ESR1:ESR2</em> ratios. Moreover, STX64 induced apoptosis, carboplatin triggered necrosis, and E1S potentiated both, indicating distinct cell death mechanisms. These findings emphasize the role of estrogen signaling in modulating the chemotherapy response in HGSOC. Although STX64 may not consistently enhance carboplatin effects, its strong pro-apoptotic activity and selective efficacy in ER-positive cells, highlight its promise as a potential standalone or maintenance therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118278"},"PeriodicalIF":6.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective strategies against doxorubicin-induced cardiotoxicity: A review from standard therapies to emerging mitochondrial transplantation","authors":"Kanako Ito-Hagiwara ,&nbsp;Jun Hagiwara ,&nbsp;Yusuke Endo ,&nbsp;Lance B. Becker ,&nbsp;Kei Hayashida","doi":"10.1016/j.biopha.2025.118315","DOIUrl":"10.1016/j.biopha.2025.118315","url":null,"abstract":"<div><div>Doxorubicin (DOX), a widely used chemotherapeutic agent, is effective against a broad spectrum of malignancies but is limited by its dose-dependent and potentially irreversible cardiotoxicity. DOX-induced cardiomyopathy can lead to progressive cardiac dysfunction and heart failure, significantly impacting patient survival and quality of life. The pathogenesis of this cardiotoxicity is multifactorial, involving excessive reactive oxygen species production, mitochondrial dysfunction, calcium dysregulation, ferroptosis, DNA damage, impaired autophagy, inflammation, and cardiomyocyte death. Current cardioprotective strategies—including β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and dexrazoxane—provide only partial protection and are insufficient to fully prevent long-term cardiac damage. In recent years, mitochondria-targeted therapies have gained attention due to the central role of mitochondrial injury in DOX cardiotoxicity. Therapeutic interventions aimed at modulating mitophagy, mitochondrial dynamics, oxidative stress, and inflammation have shown promise in preclinical studies. Among these, mitochondrial transplantation (MTx) represents an innovative and emerging strategy that directly restores mitochondrial function in injured cardiomyocytes. Preclinical studies demonstrate that MTx improves cardiac function, attenuates oxidative stress, reduces apoptosis, and enhances metabolic recovery in models of this cardiotoxicity. However, several critical challenges remain, including the long-term fate of transplanted mitochondria, immune compatibility, delivery methods, and safety. This narrative review provides a comprehensive overview of the molecular mechanisms underlying anthracycline-induced cardiac injury, evaluates current and emerging therapeutic approaches, and highlights the potential of MTx as a novel, mechanistically targeted therapy. Further research is needed to overcome translational barriers and evaluate clinical efficacy in human studies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118315"},"PeriodicalIF":6.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic strategies targeting synovial cells to treat osteoarthritis","authors":"Fanfan Li,&nbsp;Jagadeesh Kumar Venkatesan,&nbsp;Henning Madry,&nbsp;Magali Cucchiarini","doi":"10.1016/j.biopha.2025.118317","DOIUrl":"10.1016/j.biopha.2025.118317","url":null,"abstract":"<div><div>Osteoarthritis is a chronic degenerative joint disorder that significantly impairs the quality of life of millions of patients and for which there is no reliable cure to date, showing the crucial need for new, effective treatments capable of alleviating this disease. Numerous studies have evidenced the critical roles played by synovial cells during the progression of the disease, including synovial macrophages and synovial fibroblasts. In response to the altered osteoarthritic environment, synovial macrophages undergo polarization towards a pro-inflammatory M1 phenotype with the secretion of inflammatory mediators and cartilage-degrading enzymes (<em>versus</em> an anti-inflammatory M2 phenotype) while synovial fibroblasts become inappropriately activated, producing inflammatory mediators and undergoing abnormal cell proliferation and migration that contribute to synovial fibrosis, aggravate inflammation, and promote angiogenesis, all exacerbating the disease. Regulating the polarization of synovial macrophages and preventing the abnormal activation of synovial fibroblasts may therefore provide adapted strategies to counteract the progression of osteoarthritis. This review recapitulates the roles of synovial cells in the disease and describes the potential of classical and more highly innovative treatments to target synovial cells <em>in vivo</em> as a means to manage the progression of osteoarthritis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118317"},"PeriodicalIF":6.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mildly uncoupling mitochondria reduces myocardial cell injury caused by hypoxia/reoxygenation","authors":"Yejing Zheng ,&nbsp;Lingxin Zheng ,&nbsp;Mengting Dai ,&nbsp;Xiaojian Tong ,&nbsp;Ziwei Wang ,&nbsp;Li Jia ,&nbsp;Yan Chen ,&nbsp;Meng Gao ,&nbsp;Guohua Gong","doi":"10.1016/j.biopha.2025.118310","DOIUrl":"10.1016/j.biopha.2025.118310","url":null,"abstract":"<div><div>Ischemia<img>reperfusion is a common cause of myocardial injury, and there are currently no clinically approved drugs for its treatment. Oxidative stress caused by mitochondrial ROS is the main cause of cell damage in ischemia<img>reperfusion (I/R). Therefore, exploring methods to reduce mitochondrial ROS during I/R is essential. Here, we investigated the effects of a low concentration of the uncoupler FCCP on hypoxia/reoxygenation (H/R) injury in myocardial cells. An in vitro myocardial I/R model was constructed by using sodium sulfite (Na₂SO₃) to induce hypoxia and then reoxygenation. We found that after hypoxia, treatment with 5 nM FCCP induced the expression of UCP1, which uncouples mitochondria, thereby decreasing ATP production, ROS levels, and mitophagy, ultimately reducing myocardial injury. In vivo experiments further revealed that 1 mg/kg body weight FCCP has a protective effect against myocardial I/R injury. These data indicated that mildly uncoupling mitochondria via a low concentration of FCCP attenuated I/R-triggered cardiac injury.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118310"},"PeriodicalIF":6.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of lncRNAs and mRNAs in bone marrow-derived mesenchymal stem cells under continuous and intermittent teriparatide treatment","authors":"Lucija Ana Vrščaj ,&nbsp;Janja Marc ,&nbsp;Barbara Ostanek","doi":"10.1016/j.biopha.2025.118293","DOIUrl":"10.1016/j.biopha.2025.118293","url":null,"abstract":"<div><div>A deeper understanding of how teriparatide exerts its anabolic effects on bone tissue may open new avenues for osteoanabolic treatment. Our study aimed to identify long non-coding RNAs and messenger RNAs (mRNAs) regulated by teriparatide. Bone marrow mesenchymal stem cells (MSCs) were treated with teriparatide during osteogenic differentiation, and long RNA sequencing was performed. We identified 7 622 differentially expressed lncRNAs in both continuous and intermittent treatment groups compared to untreated MSCs. In intermittent treatment, the most upregulated lncRNAs were VCP, EMP1, OXA1L, LPP, and SCARB2, while in continuous treatment, they were XLOC_055533, SCARB2, HNRNPC, VCP, and CALM3. The most downregulated lncRNAs in intermittent treatment were KRTAP4–11, DUBR, MEG3, DIABLO, and ABI3BP, while in continuous treatment, they were XLOC_055164, SLC2A3, COPG1, and SMTN. Among mRNAs, the most upregulated in intermittent treatment were DNAJC25-GNG10, ZBTB4, SLC2A6, TMEM189-UBE2V1, and BDP1, whereas SLC2A6, ZBTB4, MX1, BDP1, and RSAD2 were the most upregulated in continuous treatment. The most downregulated mRNAs in intermittent treatment were PIP4K2B, GFI1B, ISY1-RAB43, AC010422.5, SESN2 and ISY1-RAB43, whereas ZDBF2, KLKB1, RPS10-NUDT3, and XLOC_055092 were the most downregulated mRNAs in continuous treatment. AC008622.2, MED17, and RNF213 emerged as the most critical lncRNAs for elucidating the mechanism of intermittent teriparatide therapy, while XLOC_055533, SPG7, and HOOK3 were highlighted as the most important lncRNAs in the continuous treatment. Additionally, we identified novel lncRNAs (KRTAP4–11, CEBPZOS, and CDC42SE2) that may have a role in teriparatide effects on MSCs. Identified lncRNAs and mRNAs could serve as therapeutic targets or diagnostic markers to improve osteoanabolic treatments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118293"},"PeriodicalIF":6.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From mechanism to therapy: How EIPA modulates dendritic cell-mediated allergic responses via IL-12b and TIM4","authors":"Yan Feng ,&nbsp;Jinna Yang ,&nbsp;Le Liu ,&nbsp;Hanqing Zhang ,&nbsp;Bailing Xie ,&nbsp;Haiyang Han ,&nbsp;Yun Liao ,&nbsp;Lihua Mo ,&nbsp;Xiangqian Luo ,&nbsp;Pingchang Yang ,&nbsp;Hui Huangfu","doi":"10.1016/j.biopha.2025.118285","DOIUrl":"10.1016/j.biopha.2025.118285","url":null,"abstract":"<div><div>Th2 polarization is a key factor in the pathogenesis of allergic diseases, particularly airway allergy (AA). However, the mechanisms underlying the regulation of Th2 remain to be fully elucidated. Ethylisopropylamiloride (EIPA) has been shown to attenuate immune inflammation. This study aims to investigate the efficacy of EIPA in suppressing AA and to elucidate its underlying mechanisms. A mouse model of airway allergy was established to evaluate the effects of EIPA on AA. Additionally, bone marrow-derived dendritic cells (BMDCs) were generated to explore how EIPA modulates the properties of dendritic cells (DCs). We observed that administration of EIPA significantly alleviated experimental airway allergy. The expression of IL-12b in airway DCs was positively correlated with the suppressive effects of EIPA. Specifically, EIPA increased the levels of TRAF binding domain-containing protein (Trabid), a deubiquitinase, and Jmjd2d, a demethylase, at the IL-12b promoter region of DCs. These changes actively upregulated the expression of IL-12b. The elevated IL-12b subsequently led to the degradation of T cell immunoglobulin molecule domain-4 (TIM4) in DCs. Consequently, the Th2 response and airway allergy were mitigated. In conclusion, EIPA attenuates the allergic response by upregulating IL-12b production, reducing TIM4 expression in DCs, and suppressing the Th2 response.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118285"},"PeriodicalIF":6.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paeoniflorin exercise-mimetic potential regulates the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways to reduce cognitive impairments and neuroinflammation in amnesic mouse model","authors":"Jae-Won Choi ,&nbsp;Ji-Hye Im ,&nbsp;Rengasamy Balakrishnan","doi":"10.1016/j.biopha.2025.118299","DOIUrl":"10.1016/j.biopha.2025.118299","url":null,"abstract":"<div><div>Microglia-mediated neuroinflammation plays a crucial role in memory and cognitive deficits and the development of early mild cognitive impairment (MCI) associated with Alzheimer’s disease (AD). Paeoniflorin (PF) has been established as an effective antioxidant and anti-apoptotic agent. This study investigated the protective effects of PF on neuroinflammation, amyloidogenesis, and memory impairments in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and a C57BL/6 J amnesic mouse model. In BV-2 microglial cells, PF treatment inhibited LPS-stimulated nitric oxide (NO) production, attenuated microglial overactivation, and suppressed the excessive release of inflammatory mediators (iNOS and COX-2) in a concentration-dependent manner. More crucially, PF regulated the LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs)—including p38, ERK, and JNK—while also suppressing NF-κB nuclear transport and inhibiting IκB-α phosphorylation. In the <em>in vivo</em> study, PF (10 or 20 mg/kg) treatment significantly improved spatial learning memory and cognitive function and ameliorated memory deficits. Furthermore, PF administration upregulated BDNF, p-CREB, Nrf2, and HO-1 expression, which are biomarkers of neuroprotective and antioxidant effects. This was accompanied by a reduction in markers of neuroinflammation (iNOS and COX-2), the inhibition of microglia and astrocytes overactivation, and decreased expression of amyloidogenic protein markers APP and BACE-1 in the hippocampus and cerebral cortex. Further, PF inhibited the LPS-promoted phosphorylation of MAPK signaling, thereby reducing the phosphorylation level of IκB-α and inhibiting NF-κB activation in the hippocampus and cerebral cortex. Our results suggest that PF confers neuroprotective effects in an LPS model of Alzheimer-associated MCI by regulating the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118299"},"PeriodicalIF":6.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parietin from lichen: extraction, characterization, and in silico, in vitro, and in vivo evaluation of its protective effects against inflammation, oxidative stress, and neutrophil infiltration in diabetic rat tissues","authors":"Faiza I.A. Abdella ,&nbsp;Tahani Y.A. Alanazia ,&nbsp;Maha Awjan Alreshidi ,&nbsp;Hessah Difallah A Al-Enazy ,&nbsp;Hissah Khashman Alshammari ,&nbsp;Khaled Hamden","doi":"10.1016/j.biopha.2025.118277","DOIUrl":"10.1016/j.biopha.2025.118277","url":null,"abstract":"<div><div>Lichen-derived Phenolic parietin (PNT) demonstrates promising anti-inflammatory and antioxidant properties with potential applications as a therapeutic agent. This study investigates, for the first time, the protective effects of PNT against obesity-induced inflammation, type 2 diabetes, oxidative stress, and tissues damages. <em>In vitro</em> and <em>in silico</em> analyses revealed strong interactions of PNT with key enzymes such as lipase, α-amylase, myeloperoxidase (MPO), phospholipase A2 (PLA2), 5-lipoxygenase (5-LO), and elastase (ELA), supported by favorable binding energies and low IC50 values. In obese rats, PNT at a dose of 100 mg/kg bw significantly reduced α-amylase and lipase activities, leading to a 19 % decrease in body weight, a 42 % reduction in blood glucose levels, and a 112 % increase in liver glycogen content, as well as oral glucose tolerance test (OGTT). Furthermore, this pigment prevents the dysregulation of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and total lipids (TL) levels in tissues and serum. PNT also suppressed immune cell infiltrationin the pancreas evidenced by histological analysis and reductions in MPO activity (and inflammatory enzyme activity (PLA2, 5-LO, and ELA). Additionally, PNT reduced stress oxidant level, as shown by decreased hydrogen peroxide (H₂O₂), thiobarbituric acid reactive substances (TBARS), and total oxidant status (TOS), while enhancing total antioxidant status (TAS). Histological analysis confirmed reduced necrosis and neutrophil infiltration in the pancreas, of PNT-treated rats. These findings highlight the potent anti-inflammatory and antioxidant properties of PNT, offering therapeutic potential for mitigating tissue damage and improving organ function in obesity and type 2 diabetes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"189 ","pages":"Article 118277"},"PeriodicalIF":6.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}