Dataset Information

Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats.

ABSTRACT:

Objectives

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 anti-oxidant 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.

SUBMITTER: Sharma S

PROVIDER: S-EPMC10083836 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats.

Sharma Sumit S Iqubal Ashif A Khan Vasim V Sharma Kalicharan K Najmi Abul Kalam AK Haque Syed Ehtaishamul SE

Iranian journal of basic medical sciences 20230101 5

<h4>Objectives</h4>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; sildenaf ...[more]

PMID: 37051097

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Project description:Chronic kidney disease (CKD) is an increasing global public health problem, with high morbidity and mortality. Jian-Pi-Yi-Shen (JPYS) formula is a representative traditional Chinese medicine formula in the treatment of CKD, which is widely used in clinical practice in China. However, the underlying mechanism has not been well elucidated. In the present study, we measured the markers of apoptosis, inflammation, oxidative stress, and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to investigate the effects of JPYS formula on renal function and fibrosis and its molecular mechanism in an established animal model of 5/6 nephrectomized (5/6Nx) rats. The results demonstrated that the JPYS formula exerted a significant preventive effect on renal dysfunction and fibrosis, based on analysis of correlative parameters such as urinary protein, SCr, BUN, glomerular sclerosis index, and tubulointerstitial fibrosis score and renal histopathology and ultrastructural pathology of CKD rats. JPYS formula also induced downregulation of gene expression associated with fibrosis, such as TGF-β and type I, III, and IV collagen. Moreover, the JPYS formula showed a significant protective effect in suppressing cell apoptosis according to the results of apoptotic indexes, including increased gene expression of Bcl-2, decreased gene expression of Bax, caspase 3, caspase 9, and the number of TUNEL-positive cells. JPYS formula also ameliorated the activation of the NF-κB-mediated inflammatory pathway, as manifested by the downregulation of gene expression of TNF-α, IL-1β, IκBα, NF-κB p65, MCP-1, CXCL1, COX-2, and iNOS in the kidney. Our evidence also suggested that the JPYS formula ameliorates oxidative stress by promoting antioxidant function according to antioxidant index indicators as an indicator of GSH, SOD, CAT, and GPx and abating excessive accumulation of the reactive oxygen species biomarkers, including ROS, TBARS, 8-oxo-dG, and MDA. The data also suggested that the JPYS formula reversed the downregulation of HO-1 and Nrf2 level and upregulation of Keap1 expression. Together, our data highlighted that the JPYS formula relieved renal oxidative injury mediated by activation of Nrf2 signaling by inhibiting inflammation and apoptosis in CKD rats.

Project description:Introduction: Diabetes Mellitus is a major health problem characterized by hyperglycemia and disturbances in metabolism and implicated in causing oxidative stress. Treatment includes administration of oral hypoglycaemic agents with lifestyle modifications, these offer glycemic control, however, present limitations about availability, affordability and side effects. Traditional anti-diabetic plants are becoming popular in management of diabetes mellitus. This study was carried out to determine the efficacy of Leptadenaia hastata in treatment of diabetes.Materials and methodsDiabetes mellitus was induced in using a single injection of streptozotocin (50 mg kg- 1 i.p.). The rats were divided into four groups of 5 rats each. Groups 3-6 received olive oil, 100 mg kg- 1 extract, 200 mg.kg- 1 extract and insulin (6IU kg- 1), respectively. 10 non-diabetic rats were grouped into two group receiving olive oil and 200 mg kg- 1 extract for 28 days. All groups were sacrificed by injecting with ketamine hydrochloride, blood was collected by cardiac puncture and centrifuged. The serum was analyzed for biochemical parameters. The liver was removed and homogenized with the supernatant of the resultant homogenate collected and used for analysis of oxidative stress enzymes.ResultsThe extract significantly decreased serum AST (p < 0.05), ALP (p < 0.001), ALT (p < 0.05), TG (p < 0.01), TC (p < 0.001), creatinine (p < 0.001). It had no effect on SOD and CAT levels but it significantly increased (p < 0.001) GSH levels and reduced (p < 0.05) MDA level.ConclusionsThe n-hexane extract of Leptadenia hastata significantly decreased the levels of hepatic and renal serum biomarkers proving that it was beneficial in ameliorating diabetic related complications. The extract significantly increased GSH levels and reduced MDA level.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-022-01017-z.

Dataset Information

Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats.

Objectives

Materials and methods

Results

Conclusion

Publications

Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats.

Similar Datasets

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