Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i>
<b>Background:</b> Herbal medicine represents a rich yet complex source of bioactive compounds, offering both therapeutic potential and toxicological risks. <b>Methods:</b> In this study, we systematically evaluated the biological effects of three traditional herbal extracts—...
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2025-07-01
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| author | Anna Hu Qinghao Meng Robert P. Borris Hyun-Min Kim |
| author_facet | Anna Hu Qinghao Meng Robert P. Borris Hyun-Min Kim |
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| description | <b>Background:</b> Herbal medicine represents a rich yet complex source of bioactive compounds, offering both therapeutic potential and toxicological risks. <b>Methods:</b> In this study, we systematically evaluated the biological effects of three traditional herbal extracts—<i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i>—using <i>Caenorhabditis elegans</i> as an in vivo model. <b>Results:</b> 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 (<i>atm-1</i>, <i>atl-1</i>), 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-<i>O</i>-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-<i>O</i>-rutinoside contributed to antioxidant activity. Notably, <i>S. orientalis</i> and <i>E. biebersteinii</i> shared 11 of 14 major constituents (79%), correlating with their similar phenotypic outcomes, while <i>M. longifolia</i> exhibited a more distinct chemical profile, possessing seven unique compounds. <b>Conclusions:</b> 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-<i>O</i>-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. |
| format | Article |
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| spelling | doaj-art-52f73cf4df4b43098f5e67093bcdfe582025-08-20T03:07:58ZengMDPI AGPharmaceuticals1424-82472025-07-01187103010.3390/ph18071030Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i>Anna Hu0Qinghao Meng1Robert P. Borris2Hyun-Min Kim3Division of Natural and Applied Sciences, Duke Kunshan University, Kunshan 215316, ChinaSchool of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, ChinaSchool of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, ChinaDivision of Natural and Applied Sciences, Duke Kunshan University, Kunshan 215316, China<b>Background:</b> Herbal medicine represents a rich yet complex source of bioactive compounds, offering both therapeutic potential and toxicological risks. <b>Methods:</b> In this study, we systematically evaluated the biological effects of three traditional herbal extracts—<i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i>—using <i>Caenorhabditis elegans</i> as an in vivo model. <b>Results:</b> 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 (<i>atm-1</i>, <i>atl-1</i>), 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-<i>O</i>-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-<i>O</i>-rutinoside contributed to antioxidant activity. Notably, <i>S. orientalis</i> and <i>E. biebersteinii</i> shared 11 of 14 major constituents (79%), correlating with their similar phenotypic outcomes, while <i>M. longifolia</i> exhibited a more distinct chemical profile, possessing seven unique compounds. <b>Conclusions:</b> 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-<i>O</i>-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.https://www.mdpi.com/1424-8247/18/7/1030<i>Mentha longifolia</i><i>Scrophularia orientalis</i><i>Echium biebersteinii</i>DNA repairmeiosisgermline development |
| spellingShingle | Anna Hu Qinghao Meng Robert P. Borris Hyun-Min Kim Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i> Pharmaceuticals <i>Mentha longifolia</i> <i>Scrophularia orientalis</i> <i>Echium biebersteinii</i> DNA repair meiosis germline development |
| title | Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i> |
| title_full | Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i> |
| title_fullStr | Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i> |
| title_full_unstemmed | Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i> |
| title_short | Herbal Extract-Induced DNA Damage, Apoptosis, and Antioxidant Effects of <i>C. elegans</i>: A Comparative Study of <i>Mentha longifolia</i>, <i>Scrophularia orientalis</i>, and <i>Echium biebersteinii</i> |
| title_sort | herbal extract induced dna damage apoptosis and antioxidant effects of i c elegans i a comparative study of i mentha longifolia i i scrophularia orientalis i and i echium biebersteinii i |
| topic | <i>Mentha longifolia</i> <i>Scrophularia orientalis</i> <i>Echium biebersteinii</i> DNA repair meiosis germline development |
| url | https://www.mdpi.com/1424-8247/18/7/1030 |
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