Borneol enhances the antidepressant effects of asiaticoside by promoting its distribution into the brain.

Asiaticoside (AS) has antidepressant effects, with poor druggability characterized with inaccessibility into the brain. Here, we assessed AS distribution in the asiaticoside-borneol formula (FAB), with AS administrated orally. High performance liquid chromatography (HPLC) was applied for AS detection. The antidepressant effects of both FAB and AS were evaluated. Rats were subjected to behavioral despair paradigms and chronic unpredictable stress model (CUS) after acute and chronic drug administration, respectively. Hippocampal 5-HT, NE, BDNF, and TNF-α levels were detected, and pathological changes were observed by H&E staining. AS was detected in rat brain tissues after FAB administration, while AS was not detected when administered alone, indicating that borneol (BOR) promoted its distribution into the rat brain. Interestingly, FAB significantly reduced the immobility time in modified forced swimming test (FST) unlike AS used as a single therapy, also reversing sucrose intake more significantly compared with AS. Furthermore, FAB upregulated BDNF and 5-HT more significantly compared with AS, which revealed a possible multi-mechanism of action.