Emodin, a Potent Anthraquinone Mitigates MPTP-Induced Parkinsons' Disease Pathology by Regulating Nrf2 and Its Downstream Targets: In Silico and In Vivo Approach

Abstract

Parkinson's disease (PD) is marked by neurodegeneration that follows the destruction of dopaminergic neurons, mainly localized to the substantia nigra. It results in debilitating motor as well as non-motor symptoms. The current study investigated the neuroprotective potential of emodin, a naturally occurring anthraquinone derivative, in a well-established model of PD in mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The key focus is the Nrf2 signaling pathway, the major defense mechanism of the cells against oxidative damage and neuroinflammation, both exacerbated in the pathology of PD. Using molecular docking, the binding affinity of emodin to Nrf2 was predicted, revealing strong interactions that suggest emodin's potential to activate Nrf2. Subsequently, in vivo experiments were conducted where MPTP-induced PD mice were treated with emodin, and additional groups received Nrf2 modulators: dimethyl fumarate (DMF) as an agonist and all-trans retinoic acid (ATRA) as an antagonist. Emodin treatment led to a significant upregulation of Nrf2 expression, a reduction in oxidative stress markers such as malondialdehyde, and notable improvements in motor and cognitive behavior. DMF co-administration enhanced emodin's neuroprotective effects, whereas ATRA diminished them, highlighting the central role of Nrf2. These findings suggest that emodin effectively targets PD pathology via the Nrf2 pathway.