Safety evaluation of ethanolic extract from aerial flowering part of spiny globe thistle (Echinops spinosus) in mice: Phytochemical screening and genotoxicity

Echinops spinosus is widely used by the population due to its therapeutic potential; however, there is no evidence in the literature that substantiates its safety. Therefore, this study aimed to identify the chemical constituents of E. spinosus extract via GC/MS analysis and evaluate its cytotoxicity and genotoxicity. Male mice were orally given three doses of E. spinosus extract (250, 500, and 1000 mg/kg) for four weeks. Blood and tissue samples were collected after the end of treatment. GC–MS results revealed 73 compounds in the E. spinosus extract, including sugars, sugar alcohols, fatty acids, organic acids, amino acids, and nitrogenous compounds. In vitro experiments revealed that E. spinosus was not cytotoxic to human colon, prostate, or breast cancer cells. In vivo experiments showed that E. spinosus extract did not significantly induce chromosomal damage in the bone marrow, primary spermatocyte, or sperm morphology abnormalities at doses up to 1000 mg/kg/day. This extract also did not induce DNA damage at doses ≤ 500 mg/kg/day in the bone marrow, spleen, testis, or spermatozoa and at 250 mg/kg/day in the liver or kidney. However, treatment with a high dose of E. spinosus caused significant disturbances in liver and kidney functions, oxidative stress indicators, comet tail formation, and histological architecture of the liver, kidney, and testis. In conclusion, E. spinosus extract is nontoxic, with an oral LD₅₀ > 5000 mg/kg. The extract showed negative genotoxicity within the safety threshold of ≤ 500 mg/kg/day and positive genotoxicity at a dose of 1000 mg/kg/day.