Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

{"title":"Calcium handling abnormalities increase arrhythmia susceptibility in DMSXL myotonic dystrophy type 1 mice.","authors":"Michael Cupelli, Vamsi Krishna Murthy Ginjupalli, Jean-Baptiste Reisqs, Yvonne Sleiman, Nabil El-Sherif, Geneviève Gourdon, Jack Puymirat, Mohamed Chahine, Mohamed Boutjdir","doi":"10.1016/j.biopha.2024.117562","DOIUrl":"10.1016/j.biopha.2024.117562","url":null,"abstract":"<p><strong>Background: </strong>Myotonic dystrophy type 1 (DM1) is a multiorgan disorder with significant cardiac involvement. ECG abnormalities, including arrhythmias, occur in 80 % of DM1 patients and are the second-most common cause of death after respiratory complications; however, the mechanisms underlying the arrhythmogenesis remain unclear. The objective of this study was to investigate the basis of the electrophysiological abnormalities in DM1 using the DMSXL mouse model.</p><p><strong>Methods: </strong>ECG parameters were evaluated at baseline and post flecainide challenge. Calcium transient and action potential parameters were evaluated in Langendorff-perfused hearts using fluorescence optical mapping. Calcium transient/sparks were evaluated in ventricular myocytes via confocal microscopy. Protein and mRNA levels for calcium handling proteins were evaluated using western blot and RT-qPCR, respectively.</p><p><strong>Results: </strong>DMSXL mice showed arrhythmic events on ECG including premature ventricular contractions and sinus block. DMSXL mice showed increased calcium transient time to peak without any change to voltage parameters. Calcium alternans and both sustained and non-sustained ventricular tachyarrhythmias were readily inducible in DMSXL mice. The confocal experiments also showed calcium transient alternans and increased frequency of calcium sparks in DMSXL cardiomyocytes. These calcium abnormalities were correlated with increased RyR2 phosphorylation without changes to the other calcium handling proteins.</p><p><strong>Conclusions: </strong>The DMSXL mouse model of DM1 exhibited enhanced arrhythmogenicity associated with abnormal intracellular calcium handling due to hyperphosphorylation of RyR2, pointing to RyR2 as a potential new therapeutic target in DM1 treatment.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117562"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic value of tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: A systematic review and meta-analysis.","authors":"Meri Torri, Adam Sandell, Ahmed Al-Samadi","doi":"10.1016/j.biopha.2024.117544","DOIUrl":"10.1016/j.biopha.2024.117544","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is experiencing a rising incidence and mortality worldwide, emphasizing the need for reliable prognostic markers. Tumor-infiltrating lymphocytes (TILs) have emerged as a promising biomarker for predicting HNSCC prognosis, yet no systematic reviews have exclusively focused on hematoxylin and eosin (H&E)-stained formalin-fixed paraffin-embedded (FFPE) samples, which are routinely used in clinical practice. This systematic review and meta-analysis followed the PRISMA guidelines to examine the prognostic value of TILs in HNSCC using H&E-stained FFPE samples. Data were pooled from 43 studies, including 26 studies in a meta-analysis, analyzing 5037 HNSCC samples. We found that a high TIL count associated with a significantly improved overall survival (OS) (HR 0.47, 95 % CI 0.41-0.55, p < 0.0001), disease-free survival (DFS) (HR 0.55, 95 % CI 0.41-0.55, p < 0.0001), and disease-specific survival (DSS) (HR 0.58, 95 % CI 0.46-0.73, p < 0.0001). The heterogeneity was moderate for the pooled analysis (OS: I² = 40 %; DFS: I² = 39 %; DSS: I² = 51 %), but low for the subgroup analysis based on tumor site in oral, oropharyngeal, laryngeal, and nasopharyngeal cancer (OS and DFS: I² = 0-14 %). This review is the first to systematically evaluate TILs in HNSCC using H&E-stained samples, confirming their prognostic value. A high TIL count is associated with improved survival outcomes, suggesting their potential as prognostic biomarkers in clinical settings.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117544"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice.","authors":"Mohaddeseh Abouhosseini Tabari, Masoumeh Houshyar, Atefeh Araghi, Navideh Mirzakhani, Giuseppe Crescenzo, Roberta Cardone, Claudia Zizzadoro","doi":"10.1016/j.biopha.2024.117541","DOIUrl":"10.1016/j.biopha.2024.117541","url":null,"abstract":"<p><p>The present study was carried out to evaluate and compare the protective potential of two well-known antioxidants of herbal origin in a mouse model of acute DIC-induced nephro- and hepatotoxicity. The tested antioxidants included lemongrass essential oil (LO) and its predominant bioactive constituent citral (CIT). A third herbal product, silymarin (SILY), was used as a reference hepato-renal protective agent. DIC administration led to elevated serum urea and creatinine levels, and prompted oxidative stress along with histopathological changes in the kidney tissue. In parallel, DIC administration increased serum liver enzyme activity, decreased total protein, albumin, and globulin levels, and caused oxidative stress with associated histopathological changes in the liver tissue. Pre-treatment with LO or CIT mitigated DIC-induced alterations in all serum biochemical markers of kidney and liver health (except albumin). High-dose LO, like SILY, within kidney and liver tissues, counteracted DIC-induced oxidative stress and histomorphological alterations. By contrast, CIT failed to mitigate DIC-induced oxidative stress in the kidneys and provided only partial control of DIC-induced oxidative stress in the liver, resulting in less efficient preservation of kidney function and liver structural integrity than LO. Besides confirming the efficacy of SILY at protecting kidneys and liver against the toxicity of DIC in a rodent species different from the one tested so far (rat), this study demonstrated the preventive properties of LO and, to a lesser extent, of CIT against DIC-induced hepato-renal toxicity in mice, supporting their developmental potential as therapeutics.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117541"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3.","authors":"Maitane Asensio, Oscar Briz, Elisa Herraez, Laura Perez-Silva, Ricardo Espinosa-Escudero, Diego Bueno-Sacristan, Ana Peleteiro-Vigil, Helen Hammer, Oliver Pötz, Onat Kadioglu, Jesus M Banales, Maria L Martinez-Chantar, Matias A Avila, Rocio I R Macias, Thomas Efferth, Jose J G Marin, Elisa Lozano","doi":"10.1016/j.biopha.2024.117533","DOIUrl":"10.1016/j.biopha.2024.117533","url":null,"abstract":"<p><strong>Aims: </strong>Drug export through ABC proteins hinders cancer response to chemotherapy. Here, we have evaluated the relevance of MRP3 (ABCC3) in cholangiocarcinoma (CCA) as a potential target to overcome drug resistance.</p><p><strong>Methods: </strong>Gene expression was analyzed in silico using the TCGA-CHOL database and experimentally (mRNA and protein) in resected CCA tumors. The effect of manipulating MRP3 function/expression was evaluated in vitro and in vivo.</p><p><strong>Results: </strong>High MRP3 expression at the plasma membrane of human CCA cells was found. MRP3 overexpression in HEK293T cells selectively impaired the cytotoxic effect of etoposide, cisplatin, SN-38, and mitoxantrone. Reduced MRP3 activity with shRNAs or pan-MRP blockers enhanced the sensitivity to these drugs. MRP3 interaction with natural and semisynthetic compounds (≈40,000) was evaluated by virtual drug screening and molecular docking. Two identified potential MRP3 inhibitors (EM-114, EM-188), and sorafenib impaired MRP3 transport activity and enhanced sensitivity of CCA cells to etoposide and cisplatin. The antitumor effect of cisplatin in the mouse xenograft model was enhanced by co-treatment with sorafenib, which was accompanied by a higher intratumor accumulation of cisplatin.</p><p><strong>Conclusions: </strong>Genetic and pharmacological MRP3 inhibition enhances the anti-CCA effect of several drugs, which constitutes a promising strategy to improve the response to chemotherapy in CCA patients.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117533"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel [¹⁸F]FPG-interleukin-2 conjugate for monitoring immune checkpoint therapy with positron emission tomography.","authors":"Pragalath Sadasivam, Siddesh V Hartimath, Shivashankar Khanapur, Boominathan Ramasamy, Peter Cheng, Chin Zan Feng, David Green, Julian L Goggi, Edward G Robins, Ran Yan","doi":"10.1016/j.biopha.2024.117617","DOIUrl":"10.1016/j.biopha.2024.117617","url":null,"abstract":"<p><p>¹⁸F-interleukin-2 based PET imaging of activated T cells serves as a potential tool for non-invasive response prediction, treatment evaluation, and patient stratification in cancer immune checkpoint therapy. Herein, we report the radiolabelling of interleukin-2 (IL-2) with a novel arginine selective bioconjugation reagent, 4-[¹⁸F]fluorophenylglyoxal ([¹⁸F]FPG). Good non-decay corrected bioconjugation efficiencies of 29 ± 4 % (n = 5) were obtained for the [¹⁸F]FPG-IL-2. [¹⁸F]FPG-IL-2 uptake by the phytohemagglutinin-activated Jurkat cells (50.5 ± 1.2 %, n = 3) was significantly higher compared to the non-activated Jurkat cells (12.9 ± 1.1 %, n = 3). The [¹⁸F]FPG-IL-2 uptake was blocked by the pre-treatment of activated Jurkat cells with excess native IL-2 (22.3 ± 2.2 %, n = 3). Dynamic PET imaging and ex vivo biodistribution study of [¹⁸F]FPG-IL-2 in healthy and CT26 tumour bearing mice demonstrated hepatobiliary and renal clearance with minimal uptake in other organs and CT26 tumours. [¹⁸F]FPG-IL-2 PET imaging was applied to non-invasively monitor immune checkpoint therapy in CT26 tumour bearing mice, treated with IgG (control), ⍺PD-1 (monotherapy), and ⍺PD-1+⍺CTLA-4 (combination therapy). Significant uptake was observed in the spleens and tumours of the mice in the combination therapy group, which was associated with increased cytotoxic CD8+ T-cell infiltration and reduced tumour volumes. [¹⁸F]FPG-IL-2 based PET imaging has the potential to monitor immune checkpoint therapy.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117617"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a novel P-glycoprotein inhibitor and pairing it with oral paclitaxel liposomes for enhanced cancer therapy.","authors":"Sikai Deng, Weiwei Li, Qiyu Chen, Jianqun Shao, Junbo Zhang, Yuji Wang, Yinghuan Li","doi":"10.1016/j.biopha.2024.117577","DOIUrl":"10.1016/j.biopha.2024.117577","url":null,"abstract":"<p><p>The mucus layer and intestine epithelium pose challenges to the bioavailability of orally administered paclitaxel (PTX). A novel P-glycoprotein inhibitor, (S)-2-decanoylamino-3-(1-naphthyl)propionyl-leucyl-valine (PgpI), was synthesized in this study. Its structure was characterized using ¹H NMR, ¹³C NMR, ESI-MS and IR spectroscopies. The efficacy and in vivo toxicity of PgpI were comprehensively evaluated by R8-PEG@PLs&PgpI, i.e., the oral combination of PgpI and octaarginine R8-PEG-DSPE modified PTX liposomes (R8-PEG@PLs), for lung cancer treatment. The joint forms between PgpI and R8-PEG@PLs were investigated and the affinity of PgpI for intestinal P-glycoprotein remained unaffected when combined externally with R8-PEG@PLs (R8-PEG@PLs&PgpI), compared to the diminished affinity for internal combination. The primary endocytic pathway for R8-PEG@PLs&PgpI in Caco-2 cells was the lipid raft, with increased percentage of macropinocytosis compared to unmodified PTX liposomes (PLs). The established physiology-based cellular kinetic models revealed that the net internalization rate of PTX was 2.3 times higher in R8-PEG@PLs&PgpI than in PLs, correlating with in vivo 2.2 times of antitumor rate. R8-PEG@PLs&PgpI may address the deficits of PLs in human lung A549 tumor-bearing mice due to the lower drug concentration than in normal mice. The external combination of R8-PEG@PLs&PgpI, offering maximal efficacy and security of PgpI, is promising for oral PTX delivery.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117577"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agmatine attenuates the severity of immunometabolic disorders by suppressing macrophage polarization: an in vivo study using an ulcerative colitis mouse model.","authors":"Suyue Zhang, Zhen Sun, Yajuan Li, Xinjian Du, Kun Qian, Le Yang, Guangyan Jia, Jiye Yin, Sha Liao, Zhe Zhou","doi":"10.1016/j.biopha.2024.117549","DOIUrl":"10.1016/j.biopha.2024.117549","url":null,"abstract":"<p><p>Agmatine, an endogenous polyamine generated by the gut microbiota, positively affects host lifespan by regulating mononuclear cell or macrophage function. Although the regulatory pathways governing monocyte/macrophage differentiation have been well studied, the influence of the microbiome and its metabolites on monocyte/macrophage function have not been fully elucidated. To address this, we aimed to investigate the mechanisms whereby agmatine inhibits immunometabolic disorders using the colon of ulcerative colitis (UC) model mice. Agmatine (10 mM) attenuated pathological damage to colonic tissue and significantly improved the survival rate of UC model mice. In particular, treatment of UC model mice with 0.4, 2, and 10 mM agmatine resulted in mortality rates of 70 %, 20 %, 10 %, and 0 %, respectively. In a macrophage-depletion model, agmatine regulated the inflammatory microenvironment by affecting macrophages: it reduced the proportion of M1 macrophages and increased that of M2 macrophages in UC model mice. In cultured macrophages, agmatine inhibited lipopolysaccharide-induced inflammatory cytokine and NO secretion, as detected by enzyme-linked immunosorbent assay and the Griess assay, respectively. Agmatine partially reduced inflammatory factor production by inhibiting histone deacetylase, as detected by fluorometric assay. These findings provide evidence that agmatine efficiently suppresses macrophage polarization in UC mice, highlighting its potential as an anti-inflammatory agent against UC.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117549"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Gastrodin against neurotoxicity based on network pharmacology, molecular docking and experimental verification.","authors":"Han Guo, Chenyang Li, Jiaojiao Zhao, Tianyuan Guo, Siruan Chen, Xia Qin, Kangsheng Zhu, Wei Zhang","doi":"10.1016/j.biopha.2024.117611","DOIUrl":"10.1016/j.biopha.2024.117611","url":null,"abstract":"<p><strong>Background: </strong>Disorders of glutamate metabolism and excessive release participat in multiple neuronal pathologies including ischemic stroke (IS), Alzheimer's disease (AD), or Parkinson's disease (PD). Recently, herbal medicines have been widely used and have shown satisfactory results in the treatment of neurological disorders. Gastrodin is a traditional Chinese medicine (TCM) used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. This research examines the neuroprotective effects of Gastrodin against glutamate-induced neurotoxicity in neuronal cells.</p><p><strong>Methods: </strong>The HERB database was used to explore the active ingredients and target genes of Gastrodia Elata. The STRING database and Cytoscape software were used to screen and construct the Protein-Protein Interaction (PPI). Furthermore, we used molecular docking to predict the potential targets of Gastrodin. The effects of Gastrodin were revealed by western blot, calcium imaging, membrane clamp, CCK8 and flow cytometry. Neuronal oxidative stress and damage were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Neuronal morphology was examined using Golgi-Cox staining. Finally, animal behavior was examined using novel object recognition and fear conditioning tests.</p><p><strong>Results: </strong>We have obtained 22 components such as TM10, TM17, TM25 (Gastrodin), and 281 targets such as AKT, EGFR, and CDK1 through network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed these genes were significantly enriched in protein phosphorylation, protein serine/threonine/tyrosine kinase activity, apoptosis and HIF-1 signaling pathways, etc. A higher affinity between Gastrodin and AKT was revealed by PPI analysis and molecular docking. Further, Gastrodin significantly inhibited Ca²⁺ influxes and excitatory synaptic transmission in cortical neurons. In addition, Gastrodin effectively alleviated neuron apoptosis, oxidative stress and damage.</p><p><strong>Conclusion: </strong>Gastrodin has neuroprotective effects against glutamate-induced neurotoxicity.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117611"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting hypoxia in combination with paclitaxel to enhance therapeutic efficacy in breast and ovarian cancer.","authors":"Laura Svajda, Ivan Ranđelović, Sára Eszter Surguta, Marcell Baranyi, Mihály Cserepes, József Tóvári","doi":"10.1016/j.biopha.2024.117601","DOIUrl":"10.1016/j.biopha.2024.117601","url":null,"abstract":"<p><p>The poor vascularization of solid tumors results in oxygen-deprived areas within the tumor mass. This phenomenon is defined as tumor hypoxia and is considered to be a major contributor to tumor progression in breast and ovarian cancers due to hypoxia-cascade-promoted increased metastasizing capacity. Hence, targeting hypoxia is a strategic cancer treatment approach, however, the hypoxia-modulating drugs face several limitations in monotherapies. Here, we investigated the impact of the potent hypoxia-inducible factor inhibitory compound acriflavine on tumor cell proliferation, migration, and metabolism under hypoxic conditions. We identified that acriflavine inhibited the proliferation of breast and ovarian tumor cells. To model the potential benefits of additional hypoxia response inhibition next to standard chemotherapy, we combined acriflavine with a frequently used chemotherapeutic agent, paclitaxel. In most breast and ovarian cancer cell lines used, we identified additive effects between the two drugs. The most significant findings were detected in triple-negative breast cancer cell lines, where we observed synergism. The drug combination effectively impeded tumor growth and metastasis formation in an in vivo orthotopic triple-negative breast cancer model as well. Additionally, we demonstrated that an epithelial-mesenchymal transition inhibitory drug, rolipram, combined with acriflavine and paclitaxel, notably reduced the motility of hypoxic triple-negative breast cancer cells. In conclusion, we identified novel drug combinations that can potentially combat triple-negative breast cancer by inhibiting hypoxia signaling and hindering cell migration and metastasis formation.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117601"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cardioprotective effects of Fruitflow® against Doxorubicin-induced toxicity in rat cardiomyoblast cells H9c2 (2-1) and high-fat diet-induced dyslipidemia and pathological alteration in cardiac tissue of Wistar Albino rats.","authors":"Diptimayee Das, Ganesan Jothimani, Antara Banerjee, Asim K Duttaroy, Surajit Pathak","doi":"10.1016/j.biopha.2024.117607","DOIUrl":"10.1016/j.biopha.2024.117607","url":null,"abstract":"<p><strong>Background: </strong>Natural compounds offer promising targets for cardioprotection, which could lead to enhanced clinical outcomes. We aimed to determine the cardioprotective effects of Fruitflow®, a water-soluble tomato extract known for its anti-platelet effects in doxorubicin-induced toxicity in rat cardiomyoblast cell line pathological alteration in heart tissue of high fat-fed Wistar Albino rats.</p><p><strong>Methods: </strong>The cardioprotective effect of Fruitflow® was investigated using H9c2 (2-1) cells (rat cardiomyoblast cell line) and high-fat diet-fed Wistar Albino rats. We evaluated morphological changes, cell proliferation, cell migration, antioxidant activity, cell cycle progression, and mitochondrial membrane potential after the Fruitflow® treatment in the Doxorubicin-injured H9c2 (2-1) cell line. We studied lipid profiles, inflammation, oxidative stress, and cardiac function regulatory enzyme activity in the rat model.</p><p><strong>Results: </strong>Fruitflow® dose-dependently stimulated cell proliferation and migration in Doxorubicin-injured H9c2 (2-1) cells, potentially promoting cardiac regeneration and supporting tissue repair. Fruitflow® modulated the cell cycle, improved mitochondrial function, and reduced oxidative stress. Furthermore, it significantly improved lipid profiles and enzyme activities and reduced inflammation and oxidative stress in high-fat-fed rats. Fruitflow® also modulated the expression of genes involved in cardiac remodeling, mitochondrial biogenesis, inflammation, and vascular function.</p><p><strong>Conclusion: </strong>Our findings suggest Fruitflow® may have cardioprotective effects, making it a potential treatment option for cardiac ailments. Larger-scale clinical trials were recommended further to determine the efficacy and safety of Fruitflow® as a potential therapeutic agent for cardiac diseases, potentially in combination with other cardioprotective medications.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117607"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}