Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of C. elegans: A Comparative Study of Mentha longifolia, Scrophularia orientalis, and Echium biebersteinii

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 18; no. 7; p. 1030
• Main Authors: Hu, Anna, Meng, Qinghao, Borris, Robert P., Kim, Hyun-Min
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.07.2025; MDPI
• Subjects: Antioxidants; Apoptosis; Biological activity; Cancer; Causes of; Chemical properties; DNA damage; DNA repair; E coli; Echium biebersteinii; Genetic aspects; Genotype & phenotype; germline development; Health aspects; Males; Materia medica, Vegetable; Medicine, Botanic; Medicine, Herbal; meiosis; Mentha longifolia; Mints (Plants); Physiological aspects; Plant extracts; Scrophularia orientalis; Sex chromosomes; Solvents; Toxicity; Worms; China; Europe; Turkey; Mentha longifolia; meiosis; Scrophularia orientalis; Echium biebersteinii; germline development; medicinal plants; DNA repair
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph18071030

Background: Herbal medicine represents a rich yet complex source of bioactive compounds, offering both therapeutic potential and toxicological risks. Methods: In this study, we systematically evaluated the biological effects of three traditional herbal extracts—Mentha longifolia, Scrophularia orientalis, and Echium biebersteinii—using Caenorhabditis elegans as an in vivo model. Results: All three extracts significantly reduced worm survival, induced larval arrest, and triggered a high incidence of males (HIM) phenotypes, indicative of mitotic failure and meiotic chromosome missegregation. Detailed analysis of germline architecture revealed extract-specific abnormalities, including nuclear disorganization, ectopic crescent-shaped nuclei, altered meiotic progression, and reduced bivalent formation. These defects were accompanied by activation of the DNA damage response, as evidenced by upregulation of checkpoint genes (atm-1, atl-1), increased pCHK-1 foci, and elevated germline apoptosis. LC-MS profiling identified 21 major compounds across the extracts, with four compounds—thymol, carvyl acetate, luteolin-7-O-rutinoside, and menthyl acetate—shared by all three herbs. Among them, thymol and carvyl acetate significantly upregulated DNA damage checkpoint genes and promoted apoptosis, whereas thymol and luteolin-7-O-rutinoside contributed to antioxidant activity. Notably, S. orientalis and E. biebersteinii shared 11 of 14 major constituents (79%), correlating with their similar phenotypic outcomes, while M. longifolia exhibited a more distinct chemical profile, possessing seven unique compounds. Conclusions: These findings highlight the complex biological effects of traditional herbal extracts, demonstrating that both beneficial and harmful outcomes can arise from specific phytochemicals within a mixture. By deconstructing these extracts into their active components, such as thymol, carvyl acetate, and luteolin-7-O-rutinoside, we gain critical insight into the mechanisms driving reproductive toxicity and antioxidant activity. This approach underscores the importance of component-level analysis for accurately assessing the therapeutic value and safety profile of medicinal plants, particularly those used in foods and dietary supplements.