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

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.

Biology of cyclooxygenase-2: An application in depression therapeutics

“…It was found that upregulation of pro-inflammatory cytokines (IL-6 and TNF-α) was seen in the hippocampus and cortex of Lipopolysaccharide (LSP)-induced depressed mice (17). Inflammatory cytokines in the blood can activate the hypothalamic-pituitary-adrenal (HPA) axis, and HPA dysfunction leads to corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), increased secretion of corticosterone (CORT) and its negative feedback dysfunction, upregulate the release of glucocorticoids(GC) and cortisol in the adrenal cortex as well as cause dysregulation of monoamine transmitters, while inflammatory factors decrease the release of glucocorticoids and cortisol through activation of indoleamine-2,3-dioxygenase (IDO) enzyme, IDO activation reduces tryptophan and increases toxic metabolites of the kynurenine pathway, which leads to damage to astrocytes, microglia, and neurons, triggering neuroinflammation, which is positively associated with Major Depressive Disorder (MDD) (18)(19)(20). In addition, inflammatory factors can also induce damage to the blood-brain barrier (BBB) and enter the brain (21,22).…”

Quantitative analysis of nutrients for nucleosides, nucleobases, and amino acids hidden behind five distinct regions‐derived Poria cocos using ultra‐performance liquid chromatography coupled with triple‐quadrupole linear ion‐trap tandem mass spectrometry

“…To prepare the stock solution [22,23], about 1 mg reference compound (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) was individually dissolved in ACN /water (9:1, v/v). Subsequently, these standard stock solutions were mixed at concentrations of 10.44, 37.12, 54.…”

“…The dwell time was at automatic set by the MultiQuant software 3.0.2(AB SCIEX Corp., Massachusetts, USA). The optimized parent and daughter ions in MRM mode were used to evaluate 19 analytes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The content of targets in all Poria cocos samples was calculated and analyzed by the Analyst 1.6.3 software SCIEX, USA).…”

“…Current evidence suggests that water-soluble polysaccharides are abundant in Poria cocos, with anti-tumor [7] and anti-oxidation [8] properties and a protective effect against intestinal injury [9], while the water-insoluble polysaccharides can be applied to treat alcoholic hepatic steatosis [10]. Besides, triterpene compounds identified in Poria cocos [11,12], reportedly have diuretic [13] and therapeutic effects against cancer [14], functional dyspepsia [11], and depression [15]. Over the years, many studies have compared multiple triterpene compounds [12,13] and polysaccharides [16,17] in Poria cocos from distinct regions.…”