Alchemilla vulgaris cytoprotection against methyl methanesulfonate by experimental and molecular docking approaches

Methyl methanesulfonate (MMS) is a chemical compound that exerts an alkylating effect on DNA and proteins. Alchemilla vulgaris L. is a medicinal plant known for its rich bioactive composition and pharmacological potential. This study investigated the cytoprotective activity of A. vulgaris extract (AVE) against MMS-induced toxicity in Allium cepa L. bulbs. For this purpose, A. cepa bulbs were divided into groups (n = 50 per group) and treated with tap water (control), AVE (250 mg/L and 500 mg/L), MMS (4000 µM), or combinations of MMS (4000 µM) with AVE (250 mg/L and 500 mg/L) for 72 h. A comprehensive analysis was conducted to ascertain the impact of the solutions on physiological parameters (rooting percentage, root elongation, and weight gain), cytogenetic endpoints (mitotic index, micronucleus formation, and chromosomal aberrations), biochemical markers (malondialdehyde, superoxide dismutase, catalase, chlorophyll a and b), and meristematic tissue integrity. Molecular docking was employed to elucidate the potential interactions between MMS and key cellular targets, including and tubulins, topoisomerases, glutamate-1-semialdehyde aminotransferase and protochlorophyllide reductase. A targeted LC-MS/MS analysis was carried out to determine the main phenolic compounds that may underlie the observed biological effects. The analysis showed that the extract predominantly contained rosmarinic acid, catechin, p-coumaric acid, rutin, and gentisic acid. MMS administration resulted in a decline in rooting percentage, weight gain, root elongation, mitotic index and chlorophyll content. MMS exposure increased frequencies of micronuclei, chromosomal aberrations, malondialdehyde levels, and the activities of superoxide dismutase and catalase. Meristematic tissue damage in the MMS group included epidermal cell deformation, flattened nuclei, cortical damage, and thickened cortex cell walls. Co-application of AVE significantly alleviated MMS-induced toxicity in a dose-dependent manner. These findings suggest that AVE exhibits notable antigenotoxic and antioxidant properties. However, further in vivo studies are needed to support its potential use in therapeutic or dietary contexts.