Trans-ferulic acid, a dietary phenolic compound, attenuates thioacetamide-induced hepatic encephalopathy by modulating oxidative stress and inflammasome signaling.

Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver failure associated with hyperammonemia, oxidative stress, and neuroinflammation. This study investigated the hepatoprotective and neuroprotective effects of trans-ferulic acid (TFA), a dietary phenolic compound, administered alone or in combination with lactulose, in a thioacetamide-induced rat model of HE. TFA treatment significantly improved liver function, reduced serum ammonia, and restored hepatic and cerebral histoarchitecture. TAA-induced motor dysfunction and altered behavioral performance were also ameliorated by TFA and lactulose, with the combination treatment producing greater overall improvement. However, these behavioral effects were interpreted in the context of concomitant locomotor impairment, particularly for spatial learning and exploratory behavior. Mechanistically, TFA enhanced antioxidant defense by activating the Nrf2/HO-1 pathway, while suppressing hepatic and cerebral inflammation through inhibition of the TLR-4/NF-κB/NLRP3 inflammasome axis. These findings demonstrate that TFA exerts dual antioxidant and anti-inflammatory actions and enhances lactulose efficacy, highlighting its potential as a functional food-derived adjunctive strategy for HE management.