Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 10;23(1):88.
doi: 10.1186/s12935-023-02936-4.

A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity

Mandeep Singh  1 , Mustafa M Kadhim  2   3 , Abduladheem Turki Jalil  4 , Shamam Kareem Oudah  5 , Zafar Aminov  6   7 , Fahad Alsaikhan  8 , Zanko Hassan Jawhar  9   10 , Andrés Alexis Ramírez-Coronel  11   12   13 , Bagher Farhood  14
Affiliations
Review

A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity

Mandeep Singh et al. Cancer Cell Int. .

Abstract

Purpose: Although doxorubicin chemotherapy is commonly applied for treating different malignant tumors, cardiotoxicity induced by this chemotherapeutic agent restricts its clinical use. The use of silymarin/silibinin may mitigate the doxorubicin-induced cardiac adverse effects. For this aim, the potential cardioprotective effects of silymarin/silibinin against the doxorubicin-induced cardiotoxicity were systematically reviewed.

Methods: In this study, we performed a systematic search in accordance with PRISMA guideline for identifying all relevant studies on "the role of silymarin/silibinin against doxorubicin-induced cardiotoxicity" in different electronic databases up to June 2022. Sixty-one articles were obtained and screened based on the predefined inclusion and exclusion criteria. Thirteen eligible papers were finally included in this review.

Results: According to the echocardiographic and electrocardiographic findings, the doxorubicin-treated groups presented a significant reduction in ejection fraction, tissue Doppler peak mitral annulus systolic velocity, and fractional shortening as well as bradycardia, prolongation of QT and QRS interval. However, these echocardiographic abnormalities were obviously improved in the silymarin plus doxorubicin groups. As well, the doxorubicin administration led to induce histopathological and biochemical changes in the cardiac cells/tissue; in contrast, the silymarin/silibinin co-administration could mitigate these induced alterations (for most of the cases).

Conclusion: According to the findings, it was found that the co-administration of silymarin/silibinin alleviates the doxorubicin-induced cardiac adverse effects. Silymarin/silibinin exerts its cardioprotective effects via antioxidant, anti-inflammatory, anti-apoptotic activities, and other mechanisms.

Keywords: Cancer; Cardiotoxicity; Doxorubicin; Silibinin; Silymarin; Systematic review.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there are no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram illustrating the selection process of studies
Fig. 2
Fig. 2
The molecular mechanisms of cardiac damage induced by doxorubicin. The doxorubicin administration leads to induction of oxidative damage, mitochondria damage, apoptosis, inflammation, and other mechanisms in the cardiac cell. In contrast, the silymarin/silibinin co-administration, through an opposite pattern, alleviates the doxorubicin-induced cardiac cell injury. ↓decreased by doxorubicin; ↑increased by doxorubicin; MDA, malondialdehyde; TBARS, thiobarbituric acid reactive substances; SOD, superoxide dismutase; POD, peroxidase; CAT, catalase; GR, glutathione reductase; GSH, glutathione; GPx, glutathione peroxidase; γ-GT, gamma-glutamyl transferase; GST, glutathione-S-transferase; NO, nitric oxide; ROS, reactive oxygen species; NF-κB, nuclear factor kappa B; IL, interleukin; iNOS, inducible nitric oxide synthase; TNF-α, tumor necrosis factor-alpha; TGF-β, transforming growth factor-beta; COX-2, cyclooxygenase-2; BAX, Bcl-2-associated X protein; AIF, apoptosis-inducing factor; PARP, poly (ADP-ribose) polymerase
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mortezaee K, Narmani A, Salehi M, Bagheri H, Farhood B, Haghi-Aminjan H, Najafi M. Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer. Life Sci. 2021;269:119020. doi: 10.1016/j.lfs.2021.119020. - DOI - PubMed
    1. Sheikholeslami S, Khodaverdian S, Dorri-Giv M, Mohammad Hosseini S, Souri S, Abedi-Firouzjah R, Zamani H, Dastranj L, Farhood B. The radioprotective effects of alpha-lipoic acid on radiotherapy-induced toxicities: a systematic review. Int Immunopharmacol. 2021;96:107741. doi: 10.1016/j.intimp.2021.107741. - DOI - PubMed
    1. Sheikholeslami S, Aryafar T, Abedi-Firouzjah R, Banaei A, Dorri-Giv M, Zamani H, Ataei G, Majdaeen M, Farhood B. The role of melatonin on radiation-induced pneumonitis and lung fibrosis: a systematic review. Life Sci. 2021;281:119721. doi: 10.1016/j.lfs.2021.119721. - DOI - PubMed
    1. Abdi Goushbolagh N, Abedi Firouzjah R, Ebrahimnejad Gorji K, Khosravanipour M, Moradi S, Banaei A, Astani A, Najafi M, Zare MH, Farhood B. Estimation of radiation dose-reduction factor for cerium oxide nanoparticles in MRC-5 human lung fibroblastic cells and MCF-7 breast-cancer cells. Artif Cells Nanomed Biotechnol. 2018;46(sup3):S1215–s1225. doi: 10.1080/21691401.2018.1536062. - DOI - PubMed
    1. Ashrafizadeh M, Farhood B, Eleojo Musa A, Taeb S, Najafi M. Damage-associated molecular patterns in tumor radiotherapy. Int Immunopharmacol. 2020;86:106761. doi: 10.1016/j.intimp.2020.106761. - DOI - PubMed