Oleuropein modulates behavioral changes, apoptosis, autophagy, inflammation, oxidative stress-associated PI3K/Akt/mTOR pathways in TAA-Induced hepatic encephalopathy

Hepatic encephalopathy (HE), which develops as a result of liver failure, is an important neurological disorder involving inflammation and oxidative damage, with apoptosis and autophagy supported mainly by experimental evidence. In the current research, we researched the protective effects of oleuropein (OLE) in a thioacetamide (TAA)-induced HE model, particularly through the PI3K/Akt/mTOR signalling pathway. To execute the planned experimental design, Sprague Dawley rats (n = 28) were divided into four groups: Control, OLE, TAA, and TAA + OLE. OLE was administered orally (50 mg/kg) during a 14-day period, followed by intraperitoneal TAA (50 mg/kg) for 14 days in the TAA groups. Behavioral tests (open field and Y-maze) were used to determine cognitive and anxiety-like disorders in the rats. Oxidative stress indicators (MDA, SOD, and GSH), pro-inflammatory cytokines (IL-1 beta, IFN-gamma, and TNF-alpha), autophagic and apoptotic processes (Caspase-3, Bcl-2, Beclin-1, LC3), PI3K/Akt/mTOR pathway proteins, and AQP4 levels were analyzed in the serum and tissue. Histopathological evaluation was used to evaluate tissue damage in the liver and brain. The results indicated that the TAA-activated PI3K/Akt/mTOR pathway was suppressed by OLE, oxidative damage, autophagy, apoptosis, and inflammation were reduced, and behavioral and histological improvements were achieved. These results suggest that OLE offers hepatoprotective effects and ameliorates HE-associated brain injury via the PI3K/Akt/mTOR pathway.

Journal

METABOLIC BRAIN DISEASE

Year

2026

Volume

41

Issue

1

ISSN

0885-7490

eISSN

1573-7365

DOI

10.1007/s11011-025-01760-1

WoS UID

WOS:001652517600001