Mechanistic Insights Into the Chemopreventive Potential of Echinops spinosus Extract and Its Butanol Fraction Against Methyl Methanesulfonate‐Induced Oxidative Stress, Genotoxicity, and Distribution in DNA Repair Gene Expression

The present work aimed to explore the protective mechanisms by which the crude extract of Echinops spinosus (CEES) and its butanol fraction (BFES) counteract methyl methanesulfonate (MMS)-induced mutagenesis. Male mice were treated orally with CEES or BFES (300 and 600 mg/kg for 7 days) with or without an intraperitoneal injection with MMS (150 mg/kg for 24 h). The findings showed that MMS treatment increased liver enzymes (ALT, AST, ALP, GGT, and LDH), serum malondialdehyde (MDA), chromosomal damage (chromosomal aberrations and micronuclei) in bone marrow and DNA damage (comet assay) in bone marrow, liver, and kidney; decreased serum glutathione S transferase (GST); and upregulated APEX1 and MGMT, without change in GADD45A expression in mouse liver. Comparable chemopreventive effects were observed when CEES or BFES (300 and 600 mg/kg) was given before MMS treatment in most biological bioassays. However, BFES, particularly low dose, was more effective than CEES in restoring APEX1 mRNA to the baseline level. In conclusion, intermediate-polarity constituents are primarily responsible for the chemopreventive activity of E. spinosus extracts through multiple cellular mechanisms, including hepatoprotective, antioxidant, genoprotective activities, and modulation of the DNA repair pathway.