Simha, P. K.; Mukherjee, C.; Gupta, V. K. G. K.; Sapariya, N. M.; Nagar, P.; Nazeer, A.; Godbole, A.; Sahu, B. S.; Upadhyay, S.

Background and aim: Huntington\'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 cordifolia and Acorus calamus are 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 procedure: We used two models, the nematode Caenorhabditis elegans and a transgenic mouse neuroblastoma cell line, both expressing mutant huntingtin proteins with elongated polyglutamines. We assessed the effect of Sida cordifolia and Acorus calamus on 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 conclusion: Here, we show that an extract of Sida cordifolia inhibits aggregation of mutant huntingtin proteins. In the C. elegans model, the extract prolonged life span and improved motility of the nematode by reducing aggregation of the mutant huntingtin protein. Acorus calamus did 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 of Sida cordifolia and its promise as a source for novel medications.