Neuroprotective Properties of Oleanolic Acid-Computational-Driven Molecular Research Combined with In Vitro and In...

Area of Science:

• Pharmacology
• Neuroscience
• Computational Chemistry

Background:

• Oleanolic acid (OA) is a plant-derived compound with potential neuroprotective and neurotoxic effects.
• Acetylcholinesterase (AChE) is a key enzyme in cholinergic neurotransmission, making it a target for neurological disorder treatments.

Purpose of the Study:

• To investigate the mechanism of OA's AChE inhibitory potential.
• To evaluate the in vitro and in vivo effects of OA on neuronal cells and model organisms.

Main Methods:

• Molecular dynamic simulations (MD) and docking were employed to study OA-AChE interactions.
• Biomimetic tests, including TLC-bioautography, were performed to determine AChE inhibitory activity.
• In vitro studies utilized SH-SY5Y human neuroblastoma cells, and in vivo studies used a zebrafish model.

Main Results:

• OA demonstrated significant AChE inhibition with an IC50 value of 9.22 μM.
• Molecular simulations revealed crucial CH-π interactions between OA and AChE active site residues.
• In vitro, OA reduced SH-SY5Y cell viability in a dose-dependent manner (IC50 = 714.32 ± 32.40 μg/mL).
• In vivo zebrafish studies showed no significant differences in mortality or morphology compared to controls (p > 0.05).

Conclusions:

• OA possesses notable AChE inhibitory properties mediated by specific molecular interactions.
• OA exhibits differential effects, with in vitro cytotoxicity but no observable in vivo toxicity in zebrafish.
• Further research is warranted to elucidate the complex neuropharmacological profile of OA.