[Targets and Molecular Mechanisms of Salidroside in Improving High-Altitude Cognitive Function]

Area of Science:

• Pharmacology
• Neuroscience
• Altitude Physiology

Context:

• High-altitude environments pose significant challenges to cognitive function due to hypoxia.
• Salidroside, a natural compound, has shown potential in mitigating these effects.
• Understanding its molecular mechanisms is crucial for therapeutic development.

Purpose:

• To elucidate the molecular targets and mechanisms of salidroside in improving high-altitude cognitive function.
• To integrate network pharmacology, molecular docking, and experimental validation.
• To identify key pathways and proteins involved in salidroside's therapeutic action.

Summary:

• Network pharmacology identified 52 common targets between salidroside and high-altitude cognitive function.
• Key targets include VEGFA, GAPDH, MMP-9, HRAS, FGF-2, HSP90AA1, and MAPK1, primarily involving PI3K-Akt, MAPK, and VEGF signaling pathways.
• Molecular docking confirmed strong binding of salidroside with GAPDH, MMP-9, and VEGFA. Experimental validation showed salidroside regulates apoptosis, autophagy, and inflammation markers in hippocampal tissues.

Impact:

• Identifies specific molecular targets and pathways through which salidroside improves cognitive function under hypoxia.
• Provides a multi-faceted approach combining computational and experimental methods for drug discovery.
• Offers potential therapeutic insights for preventing or treating cognitive deficits associated with high-altitude exposure.