Evaluation of Rhus Tox, a homeopathic formulation for treatment of Parkinson’s and Alzheimer’s disease: a network pharmacology and ex-vivo approach

Abstract

Rhus toxicodendron, commonly known as Rhus tox, is a potent homeopathic medication widely used in the treatment of rheumatoid arthritis and is claimed to have potential benefits for neurodegenerative disorders. Given the ability of homeopathic medications to address the root causes of diseases, our study aimed to evaluate Rhus tox for Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) using in-silico, ex-vivo, and network pharmacology approaches to obtain comprehensive information on its multi-component and multi-target effects. Phytoconstituents of Rhus tox were collected from PubMed and screened for ADMET properties. Targets for these constituents were predicted using the Binding Database and DisGeNET, resulting in 61 targets for Parkinsonism and 85 targets for alzhiemer’s disease. Protein-protein interactions (PPIs) were analysed using the STRING database. A Venn diagram was constructed for all these targets, and 5 out of 13 common targets were selected for docking studies. From these analyses, kaempferol and quercetin were identified as promising neuroprotective agents with good blood-brain barrier (BBB) permeation. The docking studies validated these predictions as most of the constituents showed good binding affinity with EGFR, SNCA and MAO-B. It was further validated using MAO inhibition assay, in which Quercetin was found to be highly efficacious, with an IC50 value of 32.69 μg/mL among the other flavonoids studied for MAO inhibition assay. The Rhus Tox also showed MAO inhibition assay similar to the standard seligiline. To conclude, we can propose that Rhus Tox primarily acts on the dopaminergic pathway, serotonergic pathway, and EGFR signaling pathway. Further in vitro and in vivo studies are needed to confirm the mechanism action and efficacy of Rhus Tox for treatment of neurodegenerative diseases.