Salidroside Protects Against Simazine-Induced Neurotoxicity by Activating PINK1/Parkin Mitophagy

Area of Science:

• Environmental toxicology
• Neuroscience
• Pharmacology

Background:

• Simazine (SIM), a triazine herbicide, is linked to neurotoxicity, but mechanisms are unclear.
• Salidroside (SAL), a natural antioxidant, may mitigate SIM-induced neuronal damage.
• Understanding SIM's neurotoxic pathways and SAL's protective role is crucial.

Purpose of the Study:

• To investigate SIM's neurotoxic mechanisms and SAL's protective effects using integrated network toxicology and pharmacology.
• To elucidate the role of mitophagy and apoptosis in SIM-induced neurotoxicity.
• To validate the protective potential of SAL against SIM neurotoxicity in vitro.

Main Methods:

• Integrated network toxicology and pharmacology approach.
• Bioinformatics analysis of SIM- and SAL-related targets.
• In vitro experiments using SH-SY5Y cells to assess mitochondrial function, mitophagy, and apoptosis.
• Investigation of PINK1/Parkin signaling pathway.

Main Results:

• SIM induced mitochondrial damage, metabolic dysfunction, and apoptosis in SH-SY5Y cells.
• SIM inhibited PINK1/Parkin-mediated mitophagy, leading to neurotoxicity.
• SAL restored PINK1/Parkin signaling, enhanced mitophagy, and suppressed apoptosis, protecting against SIM-induced neurotoxicity.
• SIM- and SAL-related targets were enriched in apoptosis and autophagy pathways.

Conclusions:

• SIM induces Parkinson's disease-like neurotoxicity in vitro by inhibiting mitophagy.
• SAL demonstrates significant neuroprotective effects against SIM-induced toxicity by restoring mitophagy.
• This study provides a theoretical basis for understanding SIM neurotoxicity and highlights SAL's potential therapeutic role.