Nephroprotective Effects of Silymarin: A Systematic Review and Meta-Analysis

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Negin Frounchi^1,a#, Fariba Mahmoodpoor^1,2,b#, Seyed Sina Zakavi^3,c, Kamala Eyvazova^4,d, Samira Yagubova^5,e, Mohammadreza Ardalan^1,f, Elham Ahmadian^1,g*, Ilgiz Gareev^6,h, Ozal Beylerli^6,i, and Sergey Roumiantsev^7,j

¹Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, 51665118, Iran

²Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, 33342178, Iran

³Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran

⁴Department of Surgical Diseases, Azerbaijan Medical University, Baku, 370022, Azerbaijan

⁵Department of Pathological Anatomy, Azerbaijan Medical University, Baku, 370022, Azerbaijan

⁶Educational and Scientific Institute of Neurosurgery, People’s Friendship University of Russia (RUDN University), 117198 Moscow, Russia

⁷Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia

^* To whom correspondence should be addressed.

^# These authors contributed equally to the work.

Received: March 4, 2025; Revised: April 16, 2025; Accepted: July 28, 2025

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Kidney dysfunction could impose a heavy burden on patients and society by progressing to chronic kidney disease (CKD) and end-stage renal disease, which emphasizes the importance of a search for novel agents capable of slowing down kidney disease progression or ameliorating disease outcome in patients. One of the candidates for nephroprotective agents is silymarin, a flavonoid with the anti-oxidant and anti-inflammatory properties from the milk thistle plant. We performed a systematic review of articles from Scopus, PubMed, and Web of Science that compared the nephroprotective effects of silymarin in treated and control groups (studies conducted in animals or cells were excluded). We also performed a meta-analysis of changes in the serum creatinine level and ran a subgroup analysis on the silymarin dosage, treatment duration, patients’ age, and type of kidney disease. Quality assessment of the articles was performed with the ROB2 tool. We identified 10 relevant clinical trials; meta-analysis was performed on 7 studies and showed a significant effect of silymarin on the reduction of serum creatinine levels (Hedges’ g, −1.23; 95% CI, −2.02 to −0.43; p = 0.0024; I² = 93.40%). Analysis of the subgroups revealed a significant creatinine reduction in patients with the drug-induced acute kidney injury (AKI) (p = 0.003), but not with CKD (p = 0.3065). The daily silymarin dose of 280 mg was ineffective (p = 0.2375) in reducing the creatinine levels. Despite the limitations, such as a small number of analyzed articles and their heterogeneity, we found that silymarin administration in the drug-induced AKI could provide a nephroprotective effect by lowering the serum levels of creatinine.

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KEY WORDS: silymarin, milk thistle, nephroprotective, meta-analysis, systematic review

DOI: 10.1134/S0006297925600565

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