Phytochemical Profiling and Anthelmintic Activity of Manilkara zapota L. (Chiku) Extracts: An Integrated In-vitro and In-silico Approaches

Manilkara zapota is an evergreen tree known for its medicinal value against several diseases. The current investigation was designed to assess the phytoconstituents present in hydro-ethanolic and petroleum ether extracts derived from a combination of seeds and leaves of M. zapota. Additionally, the study aimed to explore the potential free radical scavenging and the anthelmintic activities exhibited by these extracts. Phytochemical screening showed the presence of alkaloids, flavonoids, and phenolic compounds. The hydro-ethanolic extract exhibited higher concentrations of total phenolic and flavonoid contents. Specifically, the total flavonoid content in the hydro-ethanolic extract derived from a mixture of leaves and seeds was determined to be 433.6±6.62 mg of quercetin equivalent per gram of extract. In contrast, the total phenolic content was measured at 170.3±5.55 mg of gallic acid equivalent per gram of extract. In assessing antioxidant activity using the DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging assay), the hydro-ethanolic extract demonstrated notable antioxidant efficacy, surpassing the activity observed in the petroleum ether extract. Conversely, the petroleum ether extract displayed no significant antioxidant activity. The obtained hydro-ethanolic extract demonstrated notable anthelmintic properties against adult earthworm Pheretima posthuma, exhibiting a mortality rate that was highly promising when compared to the standard drug Albendazole. In parallel, a docking study was conducted, elucidating the binding interactions of all optimized compounds with various amino acid residues situated in the active site of 4MS3, identified as a GABA (gamma-aminobutyric acid) receptor in humans. Remarkably, compounds exhibiting favorable docking scores with 4MS3 demonstrated experimental anthelmintic activity comparable to their in-silico predictions. ProTox calculated and examined the toxicity prediction of the most favorable compound.