Unveiling the Neuroprotective Mechanisms of Centella Asiatica Extract Delivered via pEG Nanoparticles in TNF-α-Induced Cognitive Decline: An In Vivo Study

Introduction: Cognitive decline in the elderly is a pressing global health concern, affecting 65.6 million individuals worldwide and significantly diminishing quality of life. Elevated inflammatory markers, particularly Tumor Necrosis Factor-alpha (TNF-α), are strongly associated with neuronal damage and cognitive deterioration. Emerging evidence highlights the neuroprotective potential of natural compounds, such as those in Centella asiatica extract, known for its pharmaceutical benefits in addressing neurodegenerative diseases. Aim The research aims to evaluate the formulation’s impact on TNF-α expression and cognitive performance, focusing on its neuroprotective properties. By exploring this novel approach, the study seeks to contribute valuable insights into managing age-related cognitive decline, emphasizing TNF-α regulation as a potential therapeutic target. Results and Discussion The GC-MS analysis identified active compounds in Centella asiatica extract, including tryptamine (1.79%), γ-sitosterol, and β-sitosterol (each 7.22%), essential for cognitive improvement. These findings confirm the presence of neuroprotective agents prior to synthesis with PEG-400. On PSA, the 1:100 extract-to-PEG-400 ratio produced ideal nanoparticles (20–25 nm) optimal for blood-brain barrier (BBB) penetration. Smaller nanoparticles in this range demonstrate effective therapeutic delivery, minimizing immune clearance and degradation. T-maze tests revealed significant cognitive improvements in the 1:1 and 1:100 groups, with the latter showing the most consistent results. Flow cytometry indicated a dose-dependent reduction in TNF-α expression, with the 1:100 group achieving the greatest decrease (54.59%) compared to the control (74.65%). Conclusion The 1:100 (Centella:pEG) formulation demonstrated superior stability, bioavailability, and efficacy due to optimized nanoparticle size and consistent compound delivery, supporting Centella asiatica encapsulation as a promising neurotherapeutic strategy.