Hypericin Regulates Inflammation Levels and Improves Depressive Symptoms in Rats With Post-Stroke Depression Through the MEK/ERK/CREB Pathway.

OBJECTIVE

To investigate the effect of hypericin on ameliorating depressive behaviour in post-stroke depression (PSD) rats.

METHODS

Rats underwent a middle cerebral artery occlusion and chronic mild stress for 28 days to create a PSD model. Behavioural tests included the open field test (OFT) and the elevated plus maze test. Hypericin at a low (100 mg/kg) and a high (400 mg/kg) dose was administered via gavage. Lipopolysaccharide (LPS) was used to establish a microglia-injury model, with hypericin treatment at 0.25, 0.5, 1, and 2 μmol/L, and ELISA was used to measure serotonin (5-HT), interleukin (IL)-6 and IL-10 levels. Additionally, Western blot analysis and immunohistochemistry analysed protein levels and the expression of iNOS and Arg-1 in the hippocampus.

RESULTS

Following the PSD model preparation, the rats showed substantially reduced movement in the OFT and spent less time in the open arms of the elevated plus maze, whereas treatment with hypericin and fluoxetine improved depressive behaviour in these tests. In addition, hypericin decreased IL-6, increased IL-10 and 5-HT and enhanced p-MEK/MEK, p-ERK/ERK and p-CREB/CREB expression in the serum of the PSD rats and the LPS cell model. Hypericin also reduced iNOS but increased Arg-1 expression in the PSD rat hippocampus.

CONCLUSION

Hypericin promotes M2 microglial polarisation, reduces inflammation and improves depressive behaviour in PSD rats by activating the MEK/ERK/CREB pathway.