Pharmacological and In-Silico Investigations of Anxiolytic-like Effects of Phyllanthus Fraternus: A Probable Involvement of GABA-A Receptor

Abstract

Background:: Phyllanthus fraternus Webster Linn (family, Euphorbiaceae) is used as a traditional medication for the treatment of various disorders and has therapeutic implications. Objective:: This study intends to investigate the anxiolytic potential of Phyllanthus fraternus standardized extract and prediction of the probable role of its marker phytoconstituents. Methods:: We tested the standardized hydro-ethanolic extract of Phyllanthus fraternus (whole plant) for the Elevated plus-maze model (EPM) and Light & Dark Exploration test as classical models for anxiety. Phyto-chemical HPTLC fingerprint analysis was performed for the detection of two classes of compounds lignans and tannins. HPTLC analysis of the standardized extract was performed using phyllanthin hypophyllanthin and corilagin as marker compounds. Additionally, GABA receptor antagonism was studied in other sets of experiments to assess the involvement of this receptor in the anxiolytic- like effects produced by Phyllanthus fraternus. Results:: The lower doses of the lignan and tannin-rich extract of the Phyllanthus fraternus possess significant anxiolytic-like activity compared to the standard diazepam. Additionally, the results of the present study suggested that high doses (400mg/kg) of Phyllanthus fraternus have exerted some sedative- like effects. Phytochemical screening and HPTLC fingerprint analysis indicate the presence of lignans and tannins, whereas HPLC analysis of the standardized extract revealed the presence of marker lignan (Hypophyllanthin) and Tannin (Corilagin). The anxiolytic-like effect of Phyllanthus fraternus observed in the mice models were blocked by Flumazenil indicating the involvement of GABAA receptors in the modulation of this effect. Our molecular docking studies also supported probable anxiolytic and sedative effects. Conclusion:: To summarize, results support the use of Phyllanthus fraternus in the anxiety-like symptoms/ disease condition and suggest its anxiolytic-like effect governed by the GABA-A receptors.