For example, catalpol attenuates depression-like behaviour in pathological hyperglycaemic states, and its antidepressant mechanism is attributed to the upregulation of PI3K/AKT/Nrf2/HO-1 signalling pathway by reversing the abnormal phosphorylation of PI3K and Akt, as well as the abnormal levels of Nrf2 protein, HO-1 and superoxide dismutase, glutathione peroxidase, glutathione transferase, and reducing glutathione (Zhao et al., 2012). Here, HMOX1 is linked to major depressive disorder.