Pycnogenol attenuates thioacetamide-induced neurobehavioral impairment and hepatotoxicity via multi-target molecular modulation.

BACKGROUND

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with liver dysfunction and remains a major cause of mortality among patients with advanced liver disease. This study aimed to evaluate the protective effects of Pycnogenol in a rat model of thioacetamide-induced hepatic encephalopathy.

METHODS

Thirty-two rats were assigned to four groups: control, HE (TAA), and two treatment groups receiving Pycnogenol at 5 mg/kg and 10 mg/kg. HE was induced by intraperitoneal administration of TAA at 200 mg/kg for three consecutive days. Pycnogenol was administered orally for 14 days prior to and during TAA exposure. Behavioral tests (locomotor activity, elevated plus maze), histopathological evaluations, biochemical parameters, immunohistochemical staining, and gene expression analyses (qPCR) were performed.

RESULTS

Pycnogenol administration resulted in significant improvements in locomotor activity, reductions in oxidative stress markers, and decreased expression of IL-1β, TNF-α, NF-κB, and caspase-3. Histopathological examination revealed alleviation of hepatic and neuronal degeneration. Immunohistochemistry confirmed reduced GFAP and iNOS staining in brain tissues.

CONCLUSIONS

Pycnogenol demonstrated neuroprotective and hepatoprotective effects in this experimental model, likely through modulation of oxidative stress and inflammatory pathways. Although these findings highlight the potential translational relevance of Pycnogenol as a supportive strategy for hepatic encephalopathy, further studies in chronic models and clinical settings are required to confirm its therapeutic applicability.