Total Triterpenes of Wolfiporia cocos (Schwein.) Ryvarden & Gilb Exerts Antidepressant-Like Effects in a Chronic Unpredictable Mild Stress Rat Model and Regulates the Levels of Neurotransmitters, HPA Axis and NLRP3 Pathway.

Xiang Pan,Kezhuo Chen,Xiaochuan Ye,Jing Li,Sijie Han,Xuxiang Zhou,Dandan Zhang,Jingxian Fang,Shiqin Wang,Xinyao Luo,Lian Zhang,Hanrui Zhang

doi:10.3389/fphar.2022.793525

Xiang Pan, Kezhuo Chen + Show 10 more

Open Access

https://doi.org/10.3389/fphar.2022.793525

Copy DOI

Abstract

Purpose: Wolfiporia cocos is frequently used in traditional Chinese medicine to treat depression. However, antidepressant-like effects of the main active ingredients of Wolfiporia cocos, total triterpenes of Wolfiporia cocos (TTWC), are not well studied. This study aimed to investigate those effects and explore their specific mechanisms of action in depth. Methods: Chemical components of TTWC were analyzed using LC-MS. Depression-like behavior in rats were induced by chronic unpredictable mild stress (CUMS). The suppressive effects of TTWC (60, 120, 240 mg/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). Levels of 5-hydroxytryptamine (5-HT), glutamate (GLU), corticotropin-releasing hormone (CRH), interleukin-1 beta (IL-1beta), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in different groups were determined by ELISA. Western blotting (WB) was used to detect the expression of NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1beta, IL-1beta, pro-IL-18, and IL-18 in the prefrontal cortex. Additionally, the mRNA levels of NLRP3, ASC, caspase-1, IL-1beta and IL-18 were detected by RT-PCR. Results: A total of 69 lanostane-type triterpene acids of TTWC were identified. The results showed that TTWC exhibited an antidepressant-like effect in CUMS rats, reversed the decreased sugar preference in the SPT, reduction of immobility time in the FST, reduced the rest time, increased the total moving distance in the OFT. TTWC increased 5-HT levels and decreased GLU levels in the hippocampus. Moreover, TTWC decreased CRH levels in serum, indicating the regulation of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, reduced serum levels of IL-1beta, IL-18, IL-6, and TNF-alpha. The WB results implied that TTWC inhibited the expression of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in the prefrontal cortex and enhanced the expression of pro-caspase-1, pro-IL-1beta, and pro-IL-18. Although most of the results were not significant, PCR results showed that TTWC inhibited the expression of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in the prefrontal cortex. Conclusion: TTWC treatment exerted an antidepressant-like effect and regulates neurotransmitters, HPA axis and NLRP3 signaling pathway. These results indicated the potential of TTWC in preventing the development of depression.

Highlights

Depression, which is characterized by depressive mood or loss of anhedonia, is one of the most common and costly psychiatric disorders
We have revealed that TTWC can regulate levels of 5hydroxytryptamine (5-HT), dopamine (DA), and other neurotransmitters in the hippocampus of sleep-deprived rats in the hippocampus, inhibit the hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and relieve anxiety symptoms
The depression-like behavior in CUMS rats was assessed to examine antidepressant-like effects of TTWC using sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT)

Summary

Introduction

Depression, which is characterized by depressive mood or loss of anhedonia, is one of the most common and costly psychiatric disorders. The global prevalence of depression is high; over 264 million people of all ages worldwide suffer from depression, leading approximately 80 thousand patients to commit suicide (www.who.int). Current treatments for depression mainly focus on the monoaminergic system, and the commonly used antidepressants are selective serotonin reuptake inhibitors, or norepinephrine reuptake inhibitors. Studies have shown that one-third of patients do not respond to the initial treatment, and almost half of them have a secondary response, often producing adverse reactions such as sexual dysfunction, nausea, tremor, and insomnia (Li et al, 2020a; Zhuo et al, 2020). The identification of natural medicines with better curative effects and increased safety is urgently needed

Objectives

Methods

Results

Conclusion