Background: Bile duct ligation (BDL) is used for evaluating the protective effects of different agents with anti-inflammatory and antioxidant properties against the liver and brain damages. Naringenin (N) and melatonin (M) are used as protectants in various models of diseases.

Aims: In the current research, the combinational effects of these well-known anti-inflammatory and antioxidants agents were investigated against cerebral injuries induced by BDL in male rats.

Methods: The animals were distributed into the following groups: Sham, BDL + Vehicle and BDL+ N + M. Neuronal damages were evaluated using biochemical, motor behavioral tasks and morphological assessments.

Results: Based on the data, BDL resulted in decreasing locomotor activity, which was reversed by N and M. Morphological study confirmed that BDL led to neurodegeneration in the cortex of the rats, and the N and M treatment preserved cortical neurons. In addition, immunohistochemical (IHC) study of the rat cortex showed that BDL resulted in increasing the activated astrocytes, and the N and M treatment reduced the number of activated cells.

Conclusion: These results obviously depicted combinational therapy with N and M to exert positive effects in the BDL rats, probably due to their synergistic anti-inflammatory and antioxidant activities.