%0 Journal Article %T Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats %J Iranian Journal of Basic Medical Sciences %I Mashhad University of Medical Sciences %Z 2008-3866 %A Sharma, Sumit %A Iqubal, Ashif %A Khan, Vasim %A Sharma, Kalicharan %A Najmi, Abul Kalam %A Haque, Syed Ehtaishamul %D 2023 %\ 05/01/2023 %V 26 %N 5 %P 517-525 %! Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats %K Epimedium %K heart failure %K NF-kappaB %K Oxidative stress %K Sildenafil %R 10.22038/ijbms.2023.66481.14589 %X Objective(s): Cardiovascular diseases are widespread across the globe, and heart failure (HF) accounts for the majority of heart-associated deaths. Target-based drug therapy is much needed for the management of heart failure. We have designed this study to evaluate icariin for its cardioprotective activity in the isoproterenol (ISO) induced postinfarction model. We have randomly distributed Wistar rats into seven groups, i.e., vehicle control; isoproterenol-treated; icariin per se; sildenafil per se; ISO + icariin 5; ISO + icariin 10; and ISO + sildenafil groups. ISO (85 mg/kg, subcutaneous) was administered at 24 hr for two consecutive days to produce cardiac injury, followed by icariin administration at 5 mg/kg and 10 mg/kg orally for 56 days.Materials and Methods: Rats were subjected to hemodynamic measurements biweekly. After 24 hr of the completion of dosing, animals were sacrificed, and markers for oxidative stress, fibrosis, inflammation, and cell death were measured. Transmission electron microscopy (TEM), histopathology, and MT staining of cardiac tissue were also done to assess the pathological and fibrotic architectural damage. Results: A significant decline in hemodynamics and an antioxidant collapse were found in ISO-intoxicated rats. Alterations in the levels of cyclic guanosine monophosphate (cGMP), interleukin-10 (IL-10), Tumor necrosis factor (TNF-α), and brain natriuretic peptide (BNP) were also observed in serum. Up-regulation of caspase-3, nuclear factor (NF-ĸB), and decline in expression of nuclear factor (NrF-2) contribute to cardiac damage. The treatment with icariin and sildenafil considerably reversed the toxic changes toward normal.Conclusion: Increased cGMP and Nrf2 expression and suppressed NF-ĸB-caspase-3 signaling play a pivotal role in icariin-mediated cardioprotection.  %U https://ijbms.mums.ac.ir/article_22004_e2d905ee9f4ce1e4dc7a012a7134c4f4.pdf