Abstract
Introduction In recent years, a growing number of clinical and biological
studies have shown that patients with type 2 diabetes mellitus (T2DM) are at
increased risk of developing Parkinson’s disease (PD). Prolonged exposure to
hyperglycemia results in abnormal glucose metabolism, which in turn causes
pathological changes similar to PD, leading to selective loss of dopaminergic
neurons in the compact part of the substantia nigra. Dihydromyricetin (DHM) is a
naturally occurring flavonoid with various biological activities including
antioxidant and hepatoprotective properties. In this study, the effect of DHM on
high glucose-induced dopaminergic neuronal damage was investigated.
Methods The potential modulatory effects of DHM on high glucose-induced
dopaminergic neuronal damage and its mechanism were studied.
Results DHM ameliorated high glucose-induced dopaminergic neuronal damage
and autophagy injury. Inhibition of autophagy by 3-methyladenine abrogated the
beneficial effects of DHM on high glucose-induced dopaminergic neuronal damage.
In addition, DHM increased levels of p-AMP-activated protein kinase (AMPK) and
phosphorylated UNC51-like kinase 1. The AMPK inhibitor compound C eliminated
DHM-induced autophagy and subsequently inhibited the ameliorative effects of DHM
on high glucose-induced dopaminergic neuronal damage.
Discussion DHM ameliorates high glucose-induced dopaminergic neuronal
damage by activating the AMPK-autophagy pathway.
Keywords
dihydromyricetin - AMPK - autophagy - dopaminergic neuronal - high glucose