Depression has huge social risks of high incidence, disability, and suicide. Its prevalence and harm in people with hyperglycemia are 2–3 times higher than in normal people. However, antidepressants with precise curative effects and clear mechanisms for patients with hyperglycemia are currently lacking. Prescriptions containing Radix Rehmannia glutinosa Libosch., a traditional medicinal herb with a wide range of nutritional and medicinal values, are often used as antidepressants in Chinese clinical medicine. Catalpol is one of the main effective compounds of Radix R. glutinosa, with multiple biological activities such as hypoglycemia. Here, the antidepressant effect of catalpol on the pathological state of streptozotocin (STZ)-induced hyperglycemia and the underlying molecular mechanisms were analyzed. Results showed that administering catalpol orally to hyperglycemic mice for 21 consecutive days significantly reversed the abnormalities in tail suspension, forced swimming, and open field tests. Catalpol also reversed the abnormal phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the abnormal levels of nuclear factor erythroid 2-related factor 2 (Nrf2) protein, heme oxygenase-1 (HO-1), and antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and malondialdehyde in the hippocampus and frontal cortex of STZ-induced hyperglycemic mice. Thus, catalpol attenuates depressive-like behavior in pathological hyperglycemic state, and the antidepressant mechanism could at least be partly attributed to the upregulation of the PI3K/AKT/Nrf2/HO-1 signaling pathway in both brain regions, thus restoring the balance between oxidative and antioxidant damage. These data expanded the scientific understanding of catalpol and provided preclinical experimental evidence for its application.

抑郁症具有高发、致残、自杀等巨大社会风险。它在高血糖人群中的患病率和危害比正常人群高2-3倍。然而，目前缺乏针对高血糖患者疗效确切、机制明确的抗抑郁药。含地黄的方剂是一种具有广泛营养和药用价值的传统药材，在中医临床中常被用作抗抑郁药。梓醇是楸树的主要有效化合物之一，具有多种生物活性，如低血糖。在这里，我们分析了梓醇对链脲佐菌素 (STZ) 诱导的高血糖病理状态的抗抑郁作用及其潜在的分子机制。结果表明，连续 21 天给高血糖小鼠口服梓醇可显着逆转悬尾、强迫游泳和野外试验的异常。梓醇还逆转了磷酸肌醇 3-激酶 (PI3K) 和蛋白激酶 B (AKT) 的异常磷酸化以及核因子红细胞 2 相关因子 2 (Nrf2) 蛋白、血红素加氧酶-1 (HO-1) 的异常水平和抗氧化剂，包括超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽-s转移酶、还原型谷胱甘肽，STZ 诱导的高血糖小鼠海马和额叶皮层中的丙二醛。因此，梓醇减轻病理性高血糖状态下的抑郁样行为，其抗抑郁机制至少部分归因于两个大脑区域 PI3K/AKT/Nrf2/HO-1 信号通路的上调，从而恢复了氧化应激之间的平衡。和抗氧化损伤。这些数据扩大了对梓醇的科学认识，并为其应用提供了临床前实验证据。