Potential Anti-Depressive Effects and Mechanisms of Zhi-Zi Hou-Po Decoction Using Behavioral Despair Tests Combined With in Vitro Approaches

Yongtao Bai; Guoliang Dai; Lihua Song; Xiaolei Gu; Ning Ba; Wenzheng Ju; Wenzhou Zhang

doi:10.3389/fphar.2022.918776

Potential Anti-Depressive Effects and Mechanisms of Zhi-Zi Hou-Po Decoction Using Behavioral Despair Tests Combined With in Vitro Approaches

Front Pharmacol. 2022 Jul 6:13:918776. doi: 10.3389/fphar.2022.918776. eCollection 2022.

Authors

Yongtao Bai^{1

2}, Guoliang Dai³, Lihua Song¹, Xiaolei Gu², Ning Ba², Wenzheng Ju³, Wenzhou Zhang¹

Affiliations

¹ Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
² Clinical Research Center, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
³ Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Abstract

Zhi-Zi Hou-Po Decoction (ZHD) has been widely used in the treatment of depression for centuries. This study aimed to investigate the antidepressant effects of the water extract of ZHD (ZHD-WE) and ethanol extract of ZHD (ZHD-EE) using behavioral despair tests in mice, and to further explore the neuroprotective effects in a PC12 cell injury model induced by corticosterone (CORT). Mice were divided into a control group (normal saline), ZHD-WE groups (4, 8, and 16 g kg^-1), ZHD-EE groups (4, 8, and 16 g kg^-1) and the fluoxetine group (20 mg kg^-1). The forced swimming test (FST) and tail suspension test (TST) were used to screen the antidepressant effects of ZHD-WE and ZHD-EE after oral administration for seven consecutive days. The level of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined by ELISA. The MTT, lactate dehydrogenase (LDH) and flow cytometry analysis were performed to elucidate the neuroprotective effect of ZHD-EE on a PC12 cell injury model. Additionally, the mRNA and proteins expression of apoptotic molecules Bax, Bcl-2 and BDNF were detected by RT-PCR and western blot assay. It showed that ZHD-EE at concentrations of 8 and 16 g kg^-1 significantly decreased the immobility time in the TST and FST, and increased the BDNF levels in the hippocampus. While ZHD-WE at concentrations of 4, 8, and 16 g kg^-1 had no significant effect on the immobility time in the TST, and only the 16 g kg^-1 of extract group significantly decreased the immobility time in the FST. In vitro, the obtained results showed that PC12 cells pre-incubated with ZHD-EE at concentrations of 100 and 400 μg ml^-1 improved cell viability, decreased LDH release, and reduced apoptosis rate of PC12 cells. Moreover, ZHD-EE significantly increased the mRNA and proteins expression of Bcl-2 and BDNF, while decreased the mRNA and protein expression of Bax. ZHD-EE significantly improved despair-like behavior in mice, and its mechanism may be related to BDNF upregulation in the hippocampus. This study also showed that ZHD-EE had a protective effect on CORT-induced injury in PC12 cells by upregulating the expression of BDNF and restoring Bcl-2/Bax balance.

Keywords: BDNF (brain-derived neurotrophic factor); PC12 cells; Zhi-Zi Hou-Po Decoction; depression; mechanisms.