Parasitic nematodes, such as the zoonotic rat lungworm Angiostrongylus cantonensis, pose a significant global health burden, with current anthelmintics like albendazole showing limited efficacy. Here, we report the isolation of piplartine from Piper truncatum Vell. (Piperaceae) and its potent in vitro activity against A. cantonensis larvae. Piplartine demonstrated superior efficacy to albendazole, with EC₅₀ values of 8.3 µM for first-stage larvae (L1) and 10.4 µM for infective third-stage larvae (L3), compared to 14.2 µM (L1) and 15.6 µM (L3) for albendazole. Notably, piplartine exhibited no toxicity in the Caenorhabditis elegans model at therapeutic concentrations, underscoring its selective antiparasitic action. In silico profiling further revealed favorable drug-likeness and pharmacokinetic properties, including high gastrointestinal absorption and blood–brain barrier permeability, which are critical for targeting neurotropic infections. As the first study to characterize the activity of piplartine against A. cantonensis, our work highlights its potential as a structurally novel anthelmintic lead. Based on the obtained results, piplartine may be considered a promising and accessible candidate for combating angiostrongyliasis and related helminthic infections.

Neglected tropical diseases (NTDs) remain a major global health burden, disproportionately affecting low‐ and middle‐income regions and demanding innovative therapeutic strategies. This review summarizes current evidence on piplartine (piperlongumine), a naturally occurring amide from Piper species with broad antiparasitic and immunomodulatory properties. Studies on Schistosoma mansoni , Angiostrongylus cantonensis , Leishmania spp., Trypanosoma cruzi , Trypanosoma brucei , Plasmodium falciparum , and Toxoplasma gondii demonstrate potent activity at micromolar levels, associated with disruption of parasite redox homeostasis. In host immune cells, piplartine modulates NF‐κB and Nrf2 signaling, inhibits the immunoproteasome, and promotes antioxidant and anti‐inflammatory responses. These dual properties suggest that piplartine may influence both parasite survival and host immunopathology through redox‐sensitive mechanisms, although direct cause–effect relationships during parasitic infection remain to be experimentally established. The compound’s favorable drug‐likeness, oral bioavailability, and selective toxicity profile highlight its potential as a multitarget scaffold for the development of next‐generation therapeutics against neglected tropical and immune‐related diseases.

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.

Introduction: Schistosomiasis, caused by trematodes of the genus Schistosoma, remains a major neglected tropical disease affecting over 240 million people, mainly in low-income regions

Angiostrongylus cantonensis is the leading cause of eosinophilic meningitis worldwide, but therapeutic options remain limited. This study investigated the anthelmintic activity and preliminary selectivity of licarin A, a neolignan isolated from Nectandra oppositifolia. The compound was evaluated in vitro against first-stage (L1) larvae, infective third-stage (L3) larvae, and adult worms, using albendazole as the reference drug. Cytotoxicity was assessed in mammalian kidney epithelial, keratinocyte, and neuronal cell models, while whole-organism toxicity was examined in Caenorhabditis elegans. Physicochemical, pharmacokinetic, drug-likeness, and toxicological properties were also predicted computationally. Licarin A was active against L1 and L3 larvae, with EC₅₀ values of 16.8 and 36.4 µM, respectively. Its activity was comparable to albendazole against L1 but lower against L3, and no relevant effect was observed against adult worms (EC₅₀ > 100 µM). No detectable cytotoxicity or lethality was observed in the mammalian cell lines or C. elegans at concentrations up to 500 µM. Computational analyses indicated favorable drug-likeness, high gastrointestinal absorption, blood–brain barrier permeation, lack of recognition as a P-glycoprotein substrate, and generally low predicted toxicity. These findings identify licarin A as a selective, stage-dependent anthelmintic hit and provide a foundation for optimization of its scaffold against parasitic nematodes.