**Huiling Chen 1, Qing Huang 1,2, Shunjia Zhang 1,3, Kaiqiang Hu 1, Wenxiang Xiong 1, Lingyun Xiao 4, Renhuai Cong 4, Qingfei Liu 1,\* and Zhao Wang 1,\***


Received: 11 March 2019; Accepted: 12 April 2019; Published: 16 April 2019

**Abstract:** Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using *Panax ginseng, Angelica Sinensis, Polygala tenuifolia* Willd, and *Ziziphi spinosae* Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.

**Keywords:** major depressive disorder; Chinese herbal formula; corticosterone; BDNF; oxidative stress
