The Antidepressive and Anxiolytic Effects of Formula Consisted of Poria cocos and Cordyceps militaris Waster Medium Extract in Unpredictable Chronic Mild Stress Animal Model

According to the WHO report, depression will be the first of the global burden of diseases in 2030. There is more than fifty % of people suffered from depression and anxiety. However, only less than half of the patients receive appropriate treatments due to its side effects of the antidepressants and anxiolytics. Poria cocos (PC) and Cordyceps militaris (CM) are historically used as a complementary therapy to treat depression and anxiety because of its anti-inflammation ability. Instead of fruiting bodies, C. militaris waster medium (CMWM) is a by-product and containing a higher amount of cordycepin than fruiting bodies. Thus, this study aims to investigate the anti-depressive and anti-anxiety effects of extract formula (PC-CMWM) via the regulation of inflammation pathways. Unpredictable chronic mild stress (UCMS) model was used in this study to induce depression-like and anxiety-like behaviors in rats. The 6 weeks-old male Sprague Dawley rats were divided into five groups: control (CTL), UCMS-vehicle (NCTL), and three PC-CMWM groups (low, medium, and high dosage). The sucrose preference test and elevated plus maze (EPM) were preformed after UCMS for 35 days. The neurotransmitters (serotonin and dopamine) were measured by HPLC. The pro-inflammatory cytokines IL-1β and glutamate in the amygdala and serum were analyzed, and the proteins of p38 MAPK and NF-κB related to inflammation were evaluated by western blotting. PC-CMWM reversed the behavioral deficiency induced by UCMS exposure, including body weight loss, food intake, and sucrose preference compared to NCTL group (P < 0.05). In the EPM analysis, rats supplemented with PC-CMWM significantly increased the time spent in open arm than those in NCTL (P < 0.05). Besides, treatment with PC-CMWM significantly reduced glutamate in the amygdala and metabolic of serotonin and dopamine in the prefrontal cortex (P < 0.05) compared with NCTL. PC-CMWM improved the IL-1β in serum and reduced p38 MAPK and NF-κB protein expression in the prefrontal cortex (P < 0.05) compared with that in NCTL rats. PC-CMWM exhibited anti-depressive and anxiolytic effects via reducing inflammation and modulating neurotransmitters and it can be used as a functional food to prevent depression and anxiety. TARI1073027.