Studies on hyperglycemia-induced depression showed that catalpol (5, 10, and 20 mg/kg) reversed pathological phosphorylation of PI3K and Akt and restored Nrf2 and HO-1 levels, attributed to the upregulation of the PI3K/Akt/Nrf2/HO-1 signaling pathway [101]. The gene discussed is HMOX1; the disease is major depressive disorder.