Andrographolide as a Promising Diterpenoid Scaffold Against the Neurotropic Nematode Angiostrongylus cantonensis

Background: Angiostrongylus cantonensis is a neurotropic nematode recognized as the leading cause of eosinophilic meningitis worldwide. Despite its growing medical importance, therapeutic options for angiostrongyliasis remain limited, highlighting the need for new anthelmintic agents. Methods: The anthelmintic activity of andrographolide, a diterpene lactone isolated from Cymbopogon schoenanthus, was evaluated against first-stage (L1) larvae, infective third-stage (L3) larvae, and adult worms of A. cantonensis using motility-based phenotypic assays. Toxicity was assessed in mammalian cell models and Caenorhabditis elegans, and drug-likeness and ADMET properties were evaluated using in silico approaches. Results: Andrographolide exhibited concentration-dependent activity across all developmental stages, with EC50 values of 12.5, 11.2, and 7.3 µM for L1, L3, and adult worms, respectively. These EC50 values were similar to those of albendazole, with no statistically significant differences detected for any developmental stage. No toxicity was detected at the highest concentrations tested in mammalian cell models (CC50 > 500 µM) or C. elegans (LD50 > 1000 µM), supporting a preliminary selectivity profile. The in silico analyses predicted compliance with major drug-likeness rules, absence of PAINS alerts, high gastrointestinal absorption, and low probabilities of hepatotoxicity, nephrotoxicity, and neurotoxicity. Conclusions: Andrographolide represents a promising in vitro anthelmintic hit against A. cantonensis and warrants further preclinical investigation.