Catalpol improved OFT, FST CUMS-induced abnormalities; ↑ Hippoc PI3K, Akt, Nrf2, HO-1, TrkB, and BDNF (↓ in CUMS-rats); ↑ the Hippoc SOD, catalase, GPX, GSTs; ↑ glutathione levels, ↓ in thiobarbituric acid reactive substances level in CUMS-induced depression. This evidence concerns the gene AKT1 and major depressive disorder.