ABS 071: Therapeutic Potential of Gelsemium sempervirens and Koumine in Improving Social Interaction and Locomotion in a Preterm Birth Model

Saumik Das ¹

¹ Johns Hopkins University

Van Wickle (2025) Volume 1, ABS 071

Introduction: Each year, around 15 million infants are born premature, often resulting in birth defects that affect social interaction and motor skills. Premature birth is a leading cause of neurodevelopmental disorders, including anxiety, attention deficits, and impaired motor coordination. Despite its global prevalence, therapeutic strategies targeting behavioral and cognitive impairments associated with preterm birth remain limited.
The fruit fly, Drosophila melanogaster, serves as a powerful model organism for studying the effects of early developmental trauma, as it exhibits conserved neural pathways and behavioral phenotypes analogous to human conditions. When maternal flies are subjected to traumatic injury using a High Impact Trauma (HIT) device, their progeny display behavioral impairments such as reduced social interaction and impaired locomotion, providing a model for preterm birth-related deficits.
Social interaction in flies is assessed using a social space assay, where the distance to the nearest neighbor serves as a proxy for sociability. Locomotion is evaluated through a climbing assay that measures negative geotaxis. Gelsemium sempervirens (GS), a plant known for its anxiolytic and neuromodulatory effects, has demonstrated potential in alleviating behavioral impairments in animal models. Koumine, a primary alkaloid component of GS, is hypothesized to be the active compound responsible for these therapeutic effects.
This study investigates the impact of GS extract and koumine on social and motor behaviors in progeny of traumatically injured maternal flies. Results show that treatment with GS and koumine significantly improves both social interaction and locomotion in the offspring. These findings highlight the potential of koumine as a lead compound in drug discovery efforts targeting behavioral deficits associated with premature birth.

Methods: To model preterm birth-related behavioral deficits, Drosophila melanogaster maternal flies were subjected to traumatic injury using a High Impact Trauma (HIT) device. Injured females were then exposed to either Gelsemium sempervirens (GS) extract or varying concentrations of isolated koumine, administered via fly food. Offspring behavior was assessed 5–7 days post-eclosion. Social interaction was evaluated using a social space assay. Groups of ten flies were placed in a defined chamber, and images were captured to measure the average distance to each fly’s nearest neighbor. Reduced distance indicated greater social interaction. Locomotion was measured using a negative geotaxis climbing assay. Flies were tapped to the bottom of a vertical vial, and the number that climbed above a set threshold within ten seconds was recorded.

Results: Offspring of traumatically injured maternal flies displayed significantly reduced social interaction and impaired locomotion compared to uninjured controls. Maternal administration of Gelsemium sempervirens extract resulted in decreased average social space, indicating improved social behavior. Koumine-treated progeny showed similar reductions in inter-fly distance, confirming koumine’s role in enhancing social interaction. Climbing assay results demonstrated that offspring of treated maternal flies exhibited significantly improved negative geotaxis. Behavioral differences between control, trauma, and treatment groups were statistically analyzed using the Mann-Whitney U test, which confirmed significant improvements (p < 0.05) in both social and locomotor performance following GS and koumine treatment.

Discussion: This study demonstrates that maternal trauma in Drosophila melanogaster leads to offspring with impaired social interaction and locomotion, effectively modeling behavioral deficits seen in preterm birth. Treatment with Gelsemium sempervirens extract and koumine significantly improved these behaviors, identifying koumine as a promising candidate for neurobehavioral drug. The results validate the use of Drosophila as a high-throughput model for screening compounds targeting neurodevelopmental disorders. Future research will focus on elucidating the molecular mechanisms of koumine’s action and testing its efficacy across developmental stages and in mammalian models, bridging preclinical findings toward potential neonatal therapeutic applications.