none 10.31254/phyto.2025.14505 BioMed Research Publishers BioMed Research Publishers 16195 187186656 316921 20251216133144430 10.31254 2025-12-16T13:31:48Z 2025-12-16T13:31:46Z 0 The Journal of Phytopharmacology J Phytopharmacol 2320480X 10.31254/phyto https://www.phytopharmajournal.com/ 11 30 2025 14 5 Faaizah Afsheen https://orcid.org/0009-0008-5284-2687 MR Srinivasan https://orcid.org/0000-0003-1627-7867 K Anbukumar https://orcid.org/0000-0003-3020-4867 K Vijayarani Background: Helminthiasis in humans and livestock causes nutritional deficiency, immunosuppression, and poor productivity. The emergence of resistance to conventional anthelmintic drugs such as ivermectin, albendazole, and oxantel necessitates alternative therapeutic strategies. Naaku Poochi Kolli Kudineer Chooranam (NPK), a traditional Siddha polyherbal formulation, is reputed for its worm-expelling properties, but its mechanism of action remains unexplored. Objective: This study aimed to investigate the in silico anthelmintic potential of NPK phytochemicals against key helminthic targets-glutamate-gated chloride ion channel (GluCl), β-tubulin, and nicotinic acetylcholine receptor (nAChR), and to assess their pharmacokinetic and toxicity profiles. Materials and Methods: Phytochemicals of NPK were retrieved from the IMPPAT database and screened for physicochemical suitability (PAINS = 0, logP 1.5–4.5). Homology models of Ascaris suum β-tubulin and nAChR ACR-16 were generated using MODELER, while the GluCl structure was obtained from PDB (3RIF). Molecular docking was performed using Discovery Studio 2020 with ivermectin, albendazole, and oxantel as reference drugs. ADMET and toxicity profiles were predicted using Discovery Studio modules. Results: Of the 1687 phytochemicals screened, 225 compounds met the selection criteria. Several, including ellagic acid, luteolin, silibinin, and butein showed higher binding affinities than the reference drugs. Ellagic acid exhibited multi-target activity, binding strongly to GluCl (-101.7 kcal/mol), β-tubulin (-95 kcal/mol), and nAChR (-117.1 kcal/mol). The top compounds interacted with key residues associated with anthelmintic activity. ADMET analysis revealed that butein, butin, 2-methyl-3-glucosyloxy-5-isopropyl phenol, acetyleugenol, acetovanillone, luteolin, nigellicine, and silibinin possessed good solubility, absorption, and non-carcinogenic profiles without predicted hepatotoxicity. Conclusion: The study provides molecular evidence supporting the traditional anthelmintic use of NPK. Its phytochemicals effectively target GluCl, β-tubulin, and nAChR, suggesting potential mechanisms involving neuromuscular paralysis of parasites. These findings identify several bioactive compounds as promising, safe candidates for further in vitro and in vivo validation as next-generation plant-derived anthelmintics. 11 30 2025 335 340 1 10.31254/biomed-crossmark-policy www.biomedresearch.org false 10.31254/phyto.2025.14505 https://phytopharmajournal.com/articles/abstracts/844/year=2025&vol=14&issue=5