ETHNOPHARMACOLOGICAL RELEVANCE: Yizhi Decoction (YZD) is used in clinical medicine for the treatment of pediatric attention deficit hyperactivity disorder (ADHD).
AIM OF THE STUDY: This study aimed to determine the neuroprotective actions of YZD in the modulation of the PTEN-induced kinase 1 (PINK1)/Parkin mitophagy pathway.
MATERIALS AND METHODS: Thirty male spontaneously hypertensive rats (SHRs) were randomly allocated into five groups: an untreated group, a methylphenidate group (2 mg/kg), and three YZD treatment groups receiving low (7.5 g/kg), medium (15 g/kg), or high (30 g/kg) doses of YZD. An additional six male Wistar-Kyoto (WKY) rats constituted the control group. Prefrontal cortex neuronal morphology and quantity, apoptotic cells, mitochondrial functional integrity, and cell ultrastructural details were evaluated. Protein expression profiles related to PINK1/Parkin-driven mitophagy were analyzed by western blotting. Oxidative stress parameters, including malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG), and the GSH/GSSG ratio, were determined using commercial assay kits.
RESULTS: YZD administration resulted in a dose-dependent suppression of hyperactive and impulsive behaviors in SHRs. It mitigated neuronal injury and restored mitochondrial integrity and functional capacity in the prefrontal cortex. Additionally, YZD enhanced SOD activity, GSH content, and the GSH/GSSG ratio, while reducing MDA and GSSG levels, indicating attenuated oxidative stress and apoptosis. Notably, these protective effects correlated with decreased expression of PINK1, Parkin, LC3-II/I, and Beclin-1, alongside increased p62 expression in the prefrontal cortex.
CONCLUSION: YZD alleviates neuronal oxidative stress and damage in ADHD rat models by limiting excessive PINK1/Parkin-mediated mitophagy.
