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
http://www.doi.org/10.26538/tjnpr/v7i7.38
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 PyRxVirtual 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 Betaamyrin 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
Keywords: Anthelmintic, daf-12 receptor, Dauer diapause, Euphorbia hirta, Nauclea latifolia
quadrifida
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