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Myocardial infarction (MI) is a leading cause of death worldwide. Reperfusion is considered as an optimal therapy following cardiac ischemia. However, the promotion of a rapid elevation of O levels in ischemic cells produces high amounts of reactive oxygen species (ROS) leading to myocardial tissue injury. This phenomenon is called ischemia reperfusion injury (IRI). We aimed at identifying new and effective compounds to treat MI and minimize IRI. We previously studied heart regeneration following myocardial injury in zebrafish and described each step of the regeneration process, from the day of injury until complete recovery, in terms of transcriptional responses. Here, we mined the data and performed a deep in silico analysis to identify drugs highly likely to induce cardiac regeneration. Fisetin was identified as the top candidate. We validated its effects in an in vitro model of MI/IRI in mammalian cardiac cells. Fisetin enhances viability of rat cardiomyocytes following hypoxia/starvation - reoxygenation. It inhibits apoptosis, decreases ROS generation and caspase activation and protects from DNA damage. Interestingly, fisetin also activates genes involved in cell proliferation. Fisetin is thus a highly promising candidate drug with clinical potential to protect from ischemic damage following MI and to overcome IRI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031222 | PMC |
http://dx.doi.org/10.1038/s41598-020-59894-4 | DOI Listing |
Chemistry
December 2024
Wroclaw Medical University: Uniwersytet Medyczny im Piastow Slaskich we Wroclawiu, Department of Pharmacognosy and Herbal Medicines, Borowska 211A, 50-556, Wroclaw, POLAND.
Targeting senescent cells and the factors that accelerate this pathological state has recently emerged as a novel field in medicinal chemistry. As attention shifts to synthetic substances, studies on natural agents are often overlooked. In this paper, we present a detailed computational modeling study that encompasses quantum mechanics and molecular dynamics to elucidate the senotherapeutic activity of fisetin.
View Article and Find Full Text PDFUltrason Sonochem
December 2024
Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address:
Ischemia brain injury is closely associated with the gut microbiota. Polysaccharides, as a typical prebiotic, have been extensively employed in stroke treatment. In our previous study, Pueraria lobata polysaccharide (PLP-3) with antioxidant activity was prepared via water extraction and alcohol precipitation combined with ultrasonic degradation.
View Article and Find Full Text PDFNat Aging
December 2024
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Cellular senescence is an aging mechanism characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP). Preclinical studies demonstrate that senolytic drugs, which target survival pathways in senescent cells, can counteract age-associated conditions that span several organs. The comparative efficacy of distinct senolytic drugs for modifying aging and senescence biomarkers in vivo has not been demonstrated.
View Article and Find Full Text PDFTree Physiol
December 2024
Research Institute of Tropical Forestry, Chinese Academy of Forestry, Guangzhou, China.
Drought has been found to affect the size and color of precious heartwood of Dalbergia odorifera, but the mechanism remains unclear. For this purpose, we performed the measurement of heartwood size, color, and flavonoid content and composition in a 15-year-old mixed plantation of D. odorifera and Santalum album that had been subjected to two levels of rainfall exclusion and control treatments for seven years, and carbon isotope labeling and anatomical observation in 2-year-old potted D.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Department of Pharmacy, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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