According to the experiment, catalpol significantly increased PI3K, Akt, Nrf2, HO-1, TrkB, BNDF, and other gene and protein expression in rats modeled by CUMS, and confirmed that PI3K/Akt/Nrf2/HO-1 signaling pathways were upregulated by catalpol’s antidepressant mechanism on depression, improving hippocampal neuroprotection and antioxidant levels (Wang J et al., 2021). This evidence concerns the gene AKT1 and depressive disorder.