**5. Conclusions**

In summary, a modified TCM formula (PAPZ) protected HT22 cells from CORT-induced apoptosis. PAPZ ameliorated behavioral changes induced by chronic CORT injections in the TST, NOR, and MWM tests. The essential mechanism involved in the protective effects of PAPZ in vivo included augmentation of the BDNF level and SOD activity in the hippocampal tissue. These findings provide scientific evidence for the neuroprotective and antidepressant effects of PAPZ, which suggest potential benefits of using PAPZ in the treatment or rehabilitation of MDD patients.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2072-6643/11/4/859/s1. Figure S1: Effects of different concentrations of CORT on TH22 cell viability determined by CCK-8 assay; Table S1: Effects of different concentrations of CHFs on CORT-induced HT22 cell viability determined by CCK-8 assay.

**Author Contributions:** H.C., W.X., and Q.L. designed the experiments; Q.H. and S.Z. performed the experiments; R.C. and L.X. analyzed references and traditional medical literature; and H.C., K.H., and Z.W. wrote the manuscript.

**Acknowledgments:** This study was financially supported by grants from the National Key R&D Program of China (2018YFD0400204), the Key International S&T Cooperation Program of China (2016YFE113700), the National Key R&D Program of China (2018YFC2000304), the European Union's Horizon 2020 Research and Innovation Program (633589), and the National Natural Science Foundation of China (81471396, 81871095).

**Conflicts of Interest:** The authors declare no conflict of interest.
