Emodin ameliorates dopaminergic neuron loss in the MPP+ induced parkinson's disease model: significant inhibition of ferroptosis by activating UQCRC1 protein.

Abstract

Emodin, a naturally occurring compound derived from anthraquinone, demonstrates notable efficacy in combating oxidative stress, protecting neural tissues, and inhibiting malignant cell proliferation. This bioactive phytochemical has garnered significant scientific attention due to its multifaceted therapeutic potential, particularly in the context of oncological interventions and neurodegenerative disorder management. The neuroprotective capacity of emodin in preventing dopaminergic neuronal demise through ferroptosis modulation requires further exploration. Our experimental approach employed Erastin and MPP⁺-activated cellular systems to systematically evaluate this anthraquinone's therapeutic potential in counteracting iron-dependent programmed cell death mechanisms. Experimental data revealed that emodin effectively suppressed iron-dependent cell death through upregulation of mitochondrial complex III component UQCRC1. In MPP⁺-challenged Parkinsonian models, this compound substantially reduced degeneration of dopamine-producing neurons. Mechanistic investigations demonstrated that ferroptotic pathway activation contributes to MPP⁺-mediated neurotoxicity, while emodin counteracts this process via UQCRC1-mediated cytoprotection. These findings establish a novel regulatory axis linking UQCRC1 activation with ferroptosis inhibition, proposing emodin as a dual-function agent capable of both attenuating neuronal demise and modulating programmed cell death pathways. The pharmacological profile of emodin suggests clinical potential for intervening in ferroptosis-associated neurodegeneration.