Malvidin-3-O-Glucoside Mitigates α-Syn and MPTP Co-Induced Oxidative Stress and Apoptosis in Human Microglial HMC3 Cells

Parkinson's disease (PD) is a widespread age-related neurodegenerative disorder characterized by the presence of an aggregated protein, α-synuclein (α-syn), which is encoded by the <i>SNCA</i> gene and localized to presynaptic terminals in a normal human brain. The α-syn aggregation is induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mitochondrial neurotoxin and is therefore used to mimic PD-like pathology in various in vitro and in vivo models. However, in vitro PD-like pathology using α-syn and MPTP in human microglial cells has not yet been reported. Malvidin-3-O-glucoside (M3G) is a major anthocyanin primarily responsible for pigmentation in various fruits and beverages and has been reported to possess various bioactivities. However, the neuroprotective effects of M3G in humanized in vitro PD-like pathologies have not been reported. Therefore, individual and co-treatments of α-syn and MPTP in a human microglial (HMC3) cell line were used to establish a humanized PD-like pathology model in vitro. The individual treatments were significantly less cytotoxic when compared to the α-syn and MPTP co-treatment. This study examined the neuroprotective effects of M3G by treating HMC3 cells with α-syn (8 μg/mL) and MPTP (2 mM) individually or in a co-treatment in the presence or absence of M3G (50 μM). M3G demonstrated anti-apoptotic, anti-inflammatory, and antioxidative properties against the α-syn- and MPTP-generated humanized in vitro PD-like pathology. This study determined that the cytoprotective effects of M3G are mediated by nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling.