Protective Effect of Shenmai Injection on Doxorubicin-induced Cardiotoxicity Via Regulation of Inflammatory Mediators

Overview

Journal BMC Complement Altern Med

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2019 Nov 21

PMID 31744501

Citations 20

Authors

Sheng Zhang

Zhen-Qiang You

Lin Yang

Li-Li Li

You-Ping Wu

Li-Qiang Gu

Yan-Fei Xin

Affiliations

Soon will be listed here.

Abstract

Background: Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be involved in DOX-related cardiotoxicity. Shenmai injection (SMI), which mainly consists of Panax ginsengC.A.Mey.and Ophiopogon japonicus (Thunb.) Ker Gawl, is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis in China. In this study, we investigated the protective effect of Shenmai injection on doxorubicin-induced acute cardiac injury via the regulation of inflammatory mediators.

Methods: Male ICR mice were randomly divided into seven groups: control, DOX (10 mg/kg), SMI (5 g/kg), DOX with pretreatment with SMI (0.5 g/kg, 1.5 g/kg or 5 g/kg) and DOX with post-treatment with SMI (5 g/kg). Forty-eight hours after the last DOX administration, all mice were anesthetized for ultrasound echocardiography. Then, serum was collected for biochemical and inflammatory cytokine detection, and heart tissue was collected for histological and Western blot detection.

Results: A cumulative dose of DOX (10 mg/kg) induced acute cardiotoxicity in mice manifested by altered echocardiographic outcome, and increased tumor necrosis factor, interleukin 6 (IL-6), monocyte chemotactic protein 1, interferon-γ, and serum AST and LDH levels, as well as cardiac cytoplasmic vacuolation and myofibrillar disarrangement. DOX also caused the increase in the expression of IKK-α and iNOS and produced a large amount of NO, resulting in the accumulation of nitrotyrosine in the heart tissue. Pretreatment with SMI elicited a dose-dependent cardioprotective effect in DOX-dosed mice as evidenced by the normalization of serum inflammatory mediators, as well as improve dcardiac function and myofibril disarrangement.

Conclusions: SMI could recover inflammatory cytokine levels and suppress the expression of IKK-α and iNOS in vivo, which was increased by DOX. Overall, there was evidence that SMI could ameliorate DOX-induced cardiotoxicity by inhibiting inflammation and recovering heart dysfunction.

Citing Articles

Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.

Zhang X, Li Y, Lyu S, Jia Q, Zhang J, Liu L Chin J Integr Med. 2025; 31(3):240-250.

PMID: 39809965 DOI: 10.1007/s11655-025-4005-8.

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

Quan L, Niu W, Yang F, Zhang Y, Ding R, He Z Chin J Integr Med. 2024; .

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The cardioprotective properties of and extracts against doxorubicin-induced cardiotoxicity in mice.

Mohammad Zaki M, Helmi El-Sayed I, Abdel-Mogib M, Abdel-Hameed El-Shehawy A, El-Khawaga O Avicenna J Phytomed. 2024; 14(4):455-469.

PMID: 38952773 PMC: 11179186. DOI: 10.22038/AJP.2024.24101.

Red ginseng prevents doxorubicin-induced cardiomyopathy by inhibiting cell death via activating the Nrf2 pathway.

Yoshikawa N, Hirata N, Kurone Y, Shimoeda S Cardiooncology. 2024; 10(1):39.

PMID: 38909271 PMC: 11193215. DOI: 10.1186/s40959-024-00242-0.

Neutrophil extracellular traps mediate cardiomyocyte ferroptosis via the Hippo-Yap pathway to exacerbate doxorubicin-induced cardiotoxicity.

Zhao P, Li Y, Xu X, Yang H, Li X, Fu S Cell Mol Life Sci. 2024; 81(1):122.

PMID: 38456997 PMC: 10923748. DOI: 10.1007/s00018-024-05169-4.

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