From Kitchen Spice to Neuroprotector: The Role of 6-Shogaol in Parkinson's Disease Management

6-Shogaol (6S), the major bioactive component of ginger, exhibits diverse pharmacological properties. This study investigated the therapeutic potential of 6S against α-synuclein (α-Syn), a key pathological marker in Parkinson's disease (PD), using an in vivo methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and an in vitro lipopolysaccharide (LPS)-stimulated neuronal cell model. In vivo results showed that 6S significantly alleviated the behavioral deficits in PD mice, increased the count of tyrosine hydroxylase (TH)-positive neurons, and reduced α-Syn accumulation. Mechanistically, 6S exerted its effects by downregulating PI3K, p-Akt/Akt, and mTOR levels while upregulating LC3-II/LC3-I expression, thereby promoting autophagic activity. In vitro studies further confirmed that 6S directly interacted with the upstream protein VEGFR2, silencing VEGFR2-abrogated 6S-mediated inhibition of PI3K and α-Syn. Collectively, these findings highlight 6S as a promising functional food component for managing Parkinson's disease (PD) symptoms and targeting key pathological processes.