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Planta Med
DOI: 10.1055/a-2731-9622
DOI: 10.1055/a-2731-9622
Original Papers
Genotoxicity Studies of Milk Thistle Fruit (Silybum marianum fructus) Dry Extracts: No Hints of Mutagenicity
Authors
The authors would like to thank Kooperation Phytopharmaka GbR for supporting this study.
Abstract
Herbal medicinal products (HMPs) prepared from the fruit of Silybum marianum are mainly used in the treatment of liver diseases and dyspeptic symptoms. Despite its long-standing use and good clinical safety profile, the safety assessment of such HMPs requires special attention to toxicological aspects that are difficult to detect clinically, especially genotoxic effects. The genotoxic potential of certain S. marianum extracts has been evaluated previously; however, some in vitro assays gave inconsistent results, which is why an EU list entry was not recommended by the Herbal Medicinal Product Committee (HMPC) of the European regulatory agency EMA. To provide a more comprehensive dataset for the evaluation of the genotoxic potential, six dry extracts covering the entire polarity range of extraction solvents were chosen in accordance with the “bracketing and matrixing” approach recommended by the HMPC. These extracts were subjected to the bacterial reverse mutation test, as specified in the OECD test guideline 471, which was performed both as a pre-incubation and plate incorporation assay. When testing up to 5 mg per plate or up to the solubility or cytotoxicity limits, none of the extracts showed signs of mutagenicity, suggesting that extracts of S. marianum fruit have no genotoxic potential. Within reasonable limits, these results may be extrapolated to other extracts based on the aforementioned “bracketing and matrixing” approach.
Keywords
Silybum marianum - Carduus marianus - Asteraceae - milk thistle - genotoxicity - Ames test - bracketing and matrixing - herbal medicinal products† Passed away on the 29th of August 2025
Supporting Information
- Supporting Information (PDF) (opens in new window)
The summary statistics of the individual bacterial reverse mutation tests are provided as Supplementary Tables 1S(a – l). A summary of the qualitative results of previous bacterial reverse mutation assays of S. marianum extracts, as well as silybin, taxifolin, quercetin, and kaempferol, in comparison to the results of this study may be found in Supplementary Table 2S.
Publication History
Received: 22 May 2025
Accepted after revision: 17 October 2025
Article published online:
14 January 2026
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