Simple SummaryThis article is mainly about the development of natural medicines against the zoonotic tapeworm (Hymenolepis nana), which is caused by tapeworm eggs in infected mice, through the isolation of the components of jumbay (Leucaena leucocephala). This study allowed for an understanding of the drug therapy through the testing of these isolated components in vitro and in vivo. The authors assessed the survival and motility, and they confirmed that the two components had good effects against tapeworm. One of these components has a promising therapeutic effect in tapeworm-infected mice in the response to egg production, worm numbers, and immune responses. This article highlights the immune-enhancing and therapeutic effects of 132-hydroxy-(132-S)-pheophytin a against tapeworms in infected mice.Background/Purpose: Hymenolepis nana is globally distributed. Leucaena leucocephala has been studied as a treatment, including the nematodes and protozoa, but no research results are related to cestodes. Therefore, the aim of this study was to target H. nana. Methods: The natural components of L. leucocephala were isolated and added to H. nana, which was cultured in vitro, to observe changes in the mortality, motility, and morphology. BALB/c male mice infected with H. nana were treated with effective components of L. leucocephala for 10 days, and the changes were recorded. After the mice were sacrificed, the spleen weight was measured, and a primary culture was performed for the subsequent cytokine and chemokine testing. Results: The experiment found that 132-hydroxy-(132-S)-pheophytin a and aristophyll-C have clear cestocidal effects in vitro. 132-hydroxy-(132-S)-pheophytin a has been shown to be effective at reducing parasite populations and eliciting host immune responses in vivo. IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, MCP-1, IFN-γ, TNF-α, MIP-1α, and GM-CSF in 132-hydroxy-(132-S)-pheophytin a were significantly increased after stimulation, while IL-1α, IL-1β, IL-3, IL-12p70, and RANTES were unchanged. Conclusions: The investigation shows that components of L. leucocephala have actual cestocidal activity against H. nana.