*3.4. PAPZ Enhanced Cerebral Antioxidant Ability of Tested Mice*

Oxidative stress has been shown to cause neuronal degeneration and to play a role in the pathogenesis of anxiety and depression [30,31]. We hypothesized that PAPZ exerted neuroprotective effects by reducing cerebral oxidative stress and verified the hypothesis by SOD and MDA assays (Figure 4). Reactive oxygen species (ROS) are a kind of free radical that can damage cells through enzyme inactivation, lipid peroxidation, DNA modification, and other pathways [32]. Studies have reported that SOD is an important endogenous antioxidant enzyme and an important part of the first-line defense system against ROS [33,34]. Therefore, the SOD viability of hippocampal tissue was detected in mice. CORT treatment significantly deceased the SOD viability when compared with the control group, and PAPZ treatment significantly increased the SOD viability when compared with the CORT-treated group (Figure 4a). These results indicate that PAPZ could improve the SOD viability of mice in vivo.

**Figure 4.** PAPZ enhanced superoxide dismutase (SOD) viability and decreased malondialdehyde (MDA) level in depressive-like mice. (**a**) The SOD activity of hippocampal tissue in mice was measured by the SOD assay kit. (**b**) The MDA activity of hippocampal tissue in mice was measured by the MDA assay kit. Data from the CORT group and PAPZ+CORT group were normalized to the control group and data are expressed as mean ± SEM. \* *p* < 0.05, \*\* *p* < 0.01 represent significant differences.

MDA is a metabolite of lipid peroxidation, and its content can indirectly reflect the degree of damage of lipid peroxidation. Studies have reported that MDA concentrations in depressed patients increased when compared with healthy control groups [35,36]. The concentration of MDA in the hippocampal tissue in the CORT group significantly increased after treatment with CORT when compared with that in the control group. The change in MDA content in the PAPZ+CORT group was, as opposed to SOD, markedly decreased when compared with that in the CORT group (Figure 4b). All the results indicated that PAPZ could enhance the cerebral antioxidant ability in mice treated with CORT.
