Pharmacological repositioning of Achyranthes aspera as an antidepressant using pharmacoinformatic tools PASS and PharmaExpert: a case study with wet lab validation

Abstract

Traditional knowledge guides the use of plants for restricted therapeutic indications, but their pharmacological actions may be found beyond their ethnic therapeutic indications employing emerging computational tools. In this context, the present study was envisaged to explore the novel pharmacological effect of Achyranthes aspera (A. aspera) using PASS and PharmaExpert software tools. Based on the predicted mechanisms of the antidepressant effect for all analysed phytoconstituents of A. aspera, one may suggest its significant antidepressant action. The possible mechanism of this novel pharmacological effect is the enhancement of serotonin release, in particular caused by hexatriacontane. Therefore, pharmacological validation of the methanolic extract, hexatriacontane rich (HRF) and hexatriacontane lacking fraction (HLF) of A. aspera was carried out using the Forced Swimming Test and Tail suspension test in mice. The cortical and hippocampal monoamine and their metabolite levels were measured using high performance liquid chromatography (HPLC). A. aspera methanolic extract, HRF treatments showed a significant antidepressant effect comparable to imipramine. Further, the corresponding surge in cortical and hippocampal monoamine and their metabolite levels was also observed with these treatments. In conclusion, A. aspera has shown a significant antidepressant effect, possibly due to hexatriacontane, by raising monoamine levels.

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

“…The PASS and PASS Online (version 2022) databases predict antidepressant effects with the invariant accuracy of prediction (IAP, equivalent to an area-under-the-curve/AUC value and calculated by the leave-one-out cross-validation (LOO CV) procedure) of 0.897, yielding 90 related mechanisms of actions with the mean accuracy of prediction of ~0.977 (Supplementary Table S1). Evaluation by the PASS software of pharmacological potential of phytocomponents from St John's wort (Hypericum perforatum) and chaff-flower (Achyranthes aspera), the two well-known medicinal plants with established antidepressant effect, has also been performed [218,219]. Computational analyses of St John's wort extract activity assessed the predicted biological activity spectra for 93 phytocomponents, revealing several likely phytocomponents that may be responsible for its pharmacological (e.g., antidepressant) effects [210].…”

A comprehensive review on phytochemistry of Achyranthes aspera Linn.: An Indian medicinal plant

“…Carbohydrates namely D-glucose, D-glucuronic acid, L-rhamnose and rhamnose were identified [21]. Long chain alkanes namely 1-tritriacontanol, 17-penat triacontanol, N-hexacos-14-enoic acid, stigmasta-5,22-dien-3-ol, tritriacontane, hentriacontane, 10-tricosanone, 3-tritriacontanone, 2-octacosanone, hexatriacontane were identified [27,33]. The structures of miscellaneous compounds from A. aspera are given in Fig.…”

Therapeutic and Pharmacological Efficacy of Achyranthes aspera Linn.: An Updated Review

“…The ethanolic extract showed significant activity and triterpenoid saponins A and B played a greater role in exhibiting the pharmacological actions 85 . Due to the presence of long-chain alkanes namely hexatriacontane, the methanolic root extract of A. aspera showed greater antidepressant activity by increasing the monoamine levels 86 .…”