Post-operative cognitive dysfunction (POCD) occurs after major surgery in elderly patients and affects the quality of patients’ lives. The present study aims to explore the protective effects and possible mechanisms of compound K in old mice with POCD caused by partial hepatectomy.

Sixteen month-old mice were administered different doses of compound K from the 8th day to 14th day after partial hepatectomy. Cognitive function was subsequently measured with a Morris water-maze (MWM) test. Serum inflammatory cytokine levels were measured by magnetic bead panel; levels of cytokines in the hippocampus were analyzed using immunohistochemistry and immunoblotting. The mRNA levels of target genes were measured using real-time PCR.

Compared with the model group, MWM scores were significantly attenuated at days 10 and 14 post-surgery in mice receiving compound K (10, 30 mg/kg) in a dose-dependent manner. Both systemic and local cytokine levels were reduced after treatment of compound K. The alterations in serum lipids were independent of the attenuation of POCD syndrome. An inhibitor of liver X receptor-α (LXRα), GGPP, reversed the effects of compound K.

The results provide evidence for an alleviation of POCD by compound K via local inflammation inhibition in hippocampus tissue; furthermore, the data suggests the mechanism involves the LXRα pathway. The present study supports further evaluation of compound K as a potential effective modulator for POCD.