Therapeutic Potential of Lappula patula Extracts on Germline Development and DNA Damage Responses in C. elegans

Background: Lappula patula (L. patula) is a plant with known medicinal properties, and its extracts have shown promise as potential anti-cancer agents. This study aimed to evaluate the nematocidal effects of L. patula extracts and investigate their impact on germline development, DNA damage responses, and apoptosis in Caenorhabditis elegans (C. elegans), a model organism for studying these processes. Methods: C. elegans was exposed to L. patula extracts to assess survival, development, and incidence of male phenotype. Germline abnormalities were examined using microscopy at different developmental stages. The DNA damage response was evaluated through the expression of the atm-1, atl-1 and pCHK-1. Apoptosis was quantified by monitoring cell death during the pachytene stage. LC-MS was used to identify bioactive compounds within the extracts. Results: Exposure to L. patula extracts resulted in a dose-dependent reduction in worm survival and larval developmental progress, with no significant impact on the male incidence. Germline defects were observed, including increased nuclear spacing at premeiotic and pachytene stages, altered number of bivalents during diakinesis. These defects correlated with a significant decrease in brood size. Also, L. patula extracts activated the DNA damage response pathway, marked by increased expression of atm-1 and atl-1. Moreover, the extracts induced apoptosis in the germline in a pCHK-1-independent manner. LC-MS analysis revealed 31 potential anti-tumor compounds, supporting the extract’s cytotoxic properties. Conclusions: Lappula patula extracts exhibit potent nematocidal and cytotoxic properties, suggesting their potential for cancer therapy. The observed DNA damage and apoptosis in C. elegans emphasize the extract’s promising role in anti-cancer drug development. Further studies are needed to explore the therapeutic potential of these compounds in clinical settings.