Extract of Sapindus saponaria L ., a Native Amazonian Plant, Impacts Germ Cell Development and Modulates Longevity

ABSTRACT Sapindus saponaria L. ( S. saponaria ), popularly known as “saboeiro” or “monkey soap,” is traditionally used in South America for inflammatory, infectious, and dermatological conditions. Despite its wide use, toxicological data remain limited, and the presence of triterpenoid saponins raises safety concerns. This study evaluated the toxicological and antioxidant effects of methanolic extracts from S. saponaria leaves (ESL) and fruit pericarp (ESF) using Caenorhabditis elegans as an in vivo model. ESL and ESF were chemically profiled by ESI‐MS/MS, and worms were exposed to 1, 5, and 10 mg/mL of each extract. Endpoints included lethality (LC 50 ), survival, development, reproduction, oxidative stress resistance, lifespan, and expression of antioxidant genes ( gst‐4 , ctl‐1/2/3 ). Both extracts contained triterpenoid saponins, while glycosylated sesquiterpenes were detected only in ESF. ESL showed higher acute toxicity (LC 50 = 10.47 mg/mL) than ESF (LC 50 = 32.76 mg/mL). Survival decreased in a dose‐ and time‐dependent manner, with stronger effects in L4 worms. Reproduction was impaired by ESL at all doses and by ESF from 5 mg/mL. Body size and pharyngeal pumping were slightly reduced but not statistically significant. Under oxidative stress, ESL conferred protection mainly in L4 worms, whereas ESF was more effective in L1s. Both extracts upregulated gst‐4 , but only ESL significantly induced ctl‐1/2/3 . ESL at 5–10 mg/mL extended lifespan. Overall, S. saponaria extracts exert distinct biological effects in C. elegans . ESL displayed stronger antioxidant and pro‐longevity activity but higher toxicity, while ESF was milder and safer. These findings support the ethnopharmacological relevance of S. saponaria and provide a basis for its therapeutic exploration, highlighting the importance of extract type and concentration.