Sida cordifolia, a medicinal plant, is efficacious in models of Huntington’s disease by reducing ER stress

Abstract

ABSTRACTBackground and aimHuntington’s Disease is a severe neurodegenerative disorder caused by misfolded mutant huntingtin proteins with expanded stretches of polyglutamines aggregating and destroying cells in the nervous system.Sida cordifoliaandAcorus calamusare medicinal plants used in traditional Ayurvedic medicine to treat neurological disorders. Here, we tested the effectiveness of extracts of both medicinal plants in decreasing aggregation of mutant huntingtin protein in models of Huntington’s Disease and explored the mode of action.Experimental procedureWe used two models, the nematodeCaenorhabditis elegansand a transgenic mouse neuroblastoma cell line, both expressing mutant huntingtin proteins with elongated polyglutamines. We assessed the effect ofSida cordifoliaandAcorus calamuson mutant huntingtin protein aggregation in both models, and additionally used the cell line for mechanistic studies to identify cellular pathways underlying the effects of treatment.Results and conclusionHere, we show that an extract ofSida cordifoliainhibits aggregation of mutant huntingtin proteins. In theC. elegansmodel, the extract prolonged life span and improved motility of the nematode by reducing aggregation of the mutant huntingtin protein.Acorus calamusdid not exhibit these effects. In the transgenic mouse neuroblastoma cell line, the extract decreased aggregation of the mutant huntingtin protein by suppressing key pathways in the ER stress response caused by the mutant protein. Our results highlight the potential therapeutic value ofSida cordifoliaand its promise as a source for novel medications.HighlightsSida cordifoliaextract reduces aggregates in HD model of transgenic wormsReduction in aggregates leads to improved motility and longevitySida cordifoliaextract reduces ER stress in cells expressing mHTT proteinFirst report on the pharmacology ofSida cordifoliain neurodegeneration