β-Amyrin and Benzene-1,2,4-trimethyl from Euphorbia hirta L. and Nauclea latifolia (Smith) Leaves Induce Dauer Diapause via Antagonist Inhibition of daf-12 Receptor

Abstract

Drug development begins with medicinal plants as valuable materials. Euphorbia hirta (EH) and Nauclea latifolia (NL) are important medicinal plants having applications in the management of infectious diseases. This research aimed at evaluating EH and NL leaves for their anthelmintic property and establishment of probable dauer diapause effect induced via interaction with daf-12 nuclear receptor in worms using standard procedures. Powdered plant samples were extracted using cold maceration for 72h. Qualitative, quantitative phytochemicals and antioxidants were determined using standard procedures. Metal concentrations were determined using Atomic Absorption Spectrophotometer. Anthelmintic assay was done by observing paralysis and death times of worms. Molecular docking of compounds isolated from plants was done using PyRx-Virtual Screening Tool workspace. SwissADME of the most promising compound was done with online tool. Molecular Dynamics simulation done using UCSF Chimera and graphic processor unit (GPU) version of the PMEMD.CUDA having AMBER package. Different concentrations (10, 30, and 50 mg/mL) of methanol and hexane leaf extracts of EH and NL displayed appreciable anthelmintic activity against Pheritima pasthuma, Taenia solium and Fasciola gigantica in the following order, P. pasthuma >F. gigantica >T. solium. The antagonist effect of Beta amyrin and Benzene-1,2,4-trimethyl on the key Amino acid residues in the binding site of Daf-12 nuclear receptor confer a pronounced dauer diapause effect in EH and NL. In silico assay showed Beta-amyrin having promising activity and appreciable stability in the binding site of the target and low bioavailability. This study justifies the reasons behind EH and NL usage as anthelmintic drugs locally.