Deciphering the anthelmintic mechanisms of Operculina turpethum through integrated computational and in vitro approaches.

Abstract

Ethanobotanically, Operculina turpethum (O.T.) exhibits various therapeutic activities, including anti-inflammatory, hepatoprotective, anticancer, antiulcer, antidiabetic, and anthelmintic activity. However, the anthelmintic property lacks systematic investigation and exploration of mechanisms and responsible phytoconstituents. To elucidate the mechanistic basis of the anthelmintic activity of Operculina turpethum through in silico approaches, including ADMET profiling, molecular dynamics simulations, and KEGG pathway analysis. Additionally, to comprehensively evaluate the anthelmintic efficacy of its enriched extracts against Eisenia foetida through in vitro assays. Microwave-assisted extraction of Operculina turpethum with various solvents (petroleum ether, ethyl acetate, methanol, hydroalcoholic, and aqueous) was carried out to obtain numerous extracts. Evaluation of anthelmintic activity against Eisenia foetida earthworm using Piperazine citrate (PC) as a benchmark. Characterization of the most active extract (petroleum ether) using LC-MS. Furthermore, In silico analysis, ADMET, molecular docking, KEGG, and GO analysis of phytoconstituent with the target protein was carried out. Petroleum ether extract (PE) showed the most promising anthelmintic activity compared to other extracts and in comparison to the standard drug PC. LC-MS identified viniferifuran (VIN) and arbutin (ARB) in the PE extract. VIN exhibited the highest binding affinity (- 6.1 kcal/mol) compared to the standard PC (- 2.4 kcal/mol) and GABA ligand (- 2.9 kcal/mol) in docking studies. In silico ADMET analysis predicted VIN to be non-carcinogenic and non-mutagenic. KEGG analysis revealed Viniferifuran's involvement in cAMP, cholinergic, and calcium signaling pathways, indicating its multi-target potential in mediating anthelmintic effects. PE extract displayed significant anthelmintic activity, potentially due to VIN, which acts through a GABA-mimetic mechanism. Operculina turpethum (O.T.) holds promise as a potential source for anthelmintic drug development.