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Exploring the protective effect of Wushen Decoction on adriamycin induced cardiac toxicity based on Keap1-Nrf2/ARE signaling pathway
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DOI   10.11656/j.issn.1672-1519.2026.04.14
Key Words   Wushen Decoction;adriamycin;Keap1-Nrf2/ARE signaling pathway;cardiac toxicity
Author NameAffiliationE-mail
LYU Lieyang Department of Oncology, Wuhan Traditional Chinese Medicine Hospital, Wuhan 430000, China  
LYU Jun Department of Oncology, Wuhan Traditional Chinese Medicine Hospital, Wuhan 430000, China e97xwz@163.com 
SHE Zhuocui Department of Oncology, Wuhan Traditional Chinese Medicine Hospital, Wuhan 430000, China  
WU Di Department of Oncology, Wuhan Traditional Chinese Medicine Hospital, Wuhan 430000, China  
LIN Na Department of Oncology, Wuhan Traditional Chinese Medicine Hospital, Wuhan 430000, China  
Abstract
    [Objective] Based on the Keap1-Nrf2/antioxidant response element(ARE) signaling pathway,investigation of the protective effect of Wushen Decoction on doxorubicin(DOX)-induced cardiotoxicity. [Methods] A DOX induced rat model(DOX group) was established,and the rats were assigned into control group,DOX group,Coenzyme Q10 group(Q10 group,orally administered 30 mg/kg Coenzyme Q10),Wushen Decoction low-dose group(WSD-L group,orally administered 12.2 g/kg Wushen decoction),Wushen Decoction high-dose group(WSD-H group,orally administered 24.4 g/kg Wushen decoction),and Wushen Decoction high-dose+Nrf2 inhibitor group(WSD-H+ML-385 group,orally administered 24.4 g/kg Wushen decoction+intraperitoneal injection of 30 mg/kg Nrf2 inhibitor). The left ventricular shortening rate(FS),left ventricular end diastolic diameter(LVIDd),and left ventricular ejection fraction(LVEF),left ventricular end systolic diameter(LVIDs) ultrasound indicators were measured. Serum cardiac troponin I(cTnI),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),and myocardial tissue superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and reactive oxygen species(ROS) were detected. Hematoxylin-eosin(HE) staining was performed to observe pathological changes in myocardial tissue. TUNEL staining was performed to measure myocardial cell apoptosis. Western blot was used to measure the Keap1,Nrf2,and heme oxygenase-1(HO-1) proteins in myocardial tissue. [Results] For the control group,the DOX group showed obvious myocardial cell necrosis and inflammatory cell infiltration,mitochondrial swelling in myocardial tissue,reduced or absent cristae,nuclear membrane shrinkage,and matrix dissolution within the membrane. The LVEF,FS,and the myocardial tissue SOD,GSH-Px,Nrf2,and HO-1 were clearly reduced,while the apoptosis rate,LVIDs,LVIDd,serum CK-MB,LDH,cTnI,myocardial tissue ROS,and Keap1 protein were clearly increased(P<0.05). For the DOX group,the Q10 group,WSD-L group,and WSD-H group showed reduced pathological damage to myocardial tissue. The LVEF,FS,and the myocardial tissue SOD,GSH-Px,Nrf2,and HO-1 were obviously increased,while the apoptosis rate,LVIDs,LVIDd,serum CK-MB,LDH,cTnI,myocardial tissue ROS,and Keap1 protein were obviously reduced(P<0.05). For the WSD-H group,the myocardial tissue pathological damage in the WSD-H+ML-385 group worsened. The LVEF,FS,and the myocardial tissue SOD,GSH-Px,Nrf2,and HO-1 were clearly reduced,while the apoptosis rate,LVIDs,LVIDd,serum CK-MB,LDH,cTnI,myocardial tissue ROS,and Keap1 protein were obviously increased(P<0.05). [Conclusion] Wushen Decoction regulates the Keap1-Nrf2/ARE signaling pathway and improves adriamycin-induced cardiac toxicity in rats.

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