Antidepressant and immunosuppressive activities of two polysaccharides from Poria cocos (Schw.) Wolf

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Abstract

Pursuit of novel effective antidepressants is an urgent task. Poria cocos (Schw.) Wolf (PCW) is a traditional herb with antidepressant effects. Polysaccharides designated PCWPW and PCWPS were purified from PCW by DEAE-52 cellulose chromatography. Their structures were characterized using physicochemical and spectral methods. Chemical analysis indicated that PCWPW (37,154 Da) and PCWPS (186,209 Da) were mainly composed of mannose, glucose, galactose and fucose. Their antidepressant activities were evaluated by tail suspension test (TST), forced swimming test (FST) with chronic unpredictable mild stress (CUMS) model mice. To investigate the antidepressant mechanism, the neuroprotective and immunomodulation effects were assessed by MTT method. Results showed that PCWPW and PCWPS possess obvious antidepressant effects and can suppress ConA-stimulated T cell proliferation in a dose-dependent manner. In addition, PCWPS could protect the PC12 cells from H2O2-induced damage and suppress LPS-induced B cell proliferation. These findings implied that PCWPW and PCWPS might be a candidate for developing antidepressant or immunosuppressive agents in food and pharmaceutical industries.

Introduction

Major depressive disorder is a serious mental disorder that profoundly affects approximately 350 million people all over the world [1]. Patients with major depression have an increased onset risk of aging-related somatic diseases such as heart disease, diabetes, obesity and cancer [2]. Currently, antidepressant drugs mainly include selective serotonin-reuptake inhibitors (SSRIs), tricyclic antidepressants, monoamine oxidase inhibitors, and norepinephrine reuptake inhibitors [3,4]. However, the effects of these antidepressants are often inconsistent and many of them cause side effects [5] and drug-drug interactions, with fewer than half of patients responding well to currently available treatments [6]. Hence, the development of novel, more efficacious and low toxic antidepressants is extremely urgent.

Herbal medicine is as an important alternative and complementary therapy of western medicine system, and many of them have antidepressant activity, such as Acorus tatarinowii Schott, Morinda officinalis, Hypericum perforatum and Poria cocos (Schw.) Wolf (PCW) [7,8]. As an example, PCW is a famous medicinal fungi and nutrition food and widely distributes around the world [9,10]. In China, PCW has been used as a key component of many antidepressant prescriptions, such as Xiaoyaosan [11] and Banxia Houpu decoction [12]. Theses natural herbs often contain hundreds of compounds and may be a source for developing potential antidepressant. This fact also stimulates us to dig the active ingredients of these herbs for their antidepressant ability. In this work, we mainly focus on the effective ingredients of PCW.

Now, it has been found that the chemical compositions of PCW mainly include triterpenes, steroids, amino acids and polysaccharides [13]. Among them, different from other ingredients, polysaccharides are a classical carbohydrate polymer and have got more attention for their lower toxicities and extensive biological activities [14]. In recent studies, polysaccharides and their derivatives of PCW exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities [15].

However, there are few studies about the antidepressant ability of PCW polysaccharides. Therefore, in this work, we aim to characterize the polysaccharide components of PCW and evaluate their antidepressant activity. Firstly, DEAE-52 cellulose chromatography was used to purify PCW polysaccharides, and their structures were characterized by physicochemical and spectral methods. Secondly, the antidepressant activities of PCW polysaccharides were evaluated by tail suspension test (TST) and forced swimming test (FST) within chronic unpredictable mild stress (CUMS) model mice. Thirdly, the neuroprotective effects of PCW polysaccharides were assessed by H2O2-damaged PC12 cells. Moreover, considering the fact that many studies indicated biological activities of polysaccharides are dependent on the immunomodulation effects, we also examined the immunomodulation effects of PCW polysaccharides on splenocyte proliferation. Our results suggested that PCW polysaccharides might be a potential drug candidate for treating major depression.

Section snippets

Herbs and chemicals

Dried Poria cocos (Schw.) Wolf was purchased from Shaanxi province in China. Trifluoroacetic acid (TFA), d‑glucose, and galacturonic acid were purchased from Aladdin Reagent Int. (Shanghai, China). 3‑(4, 5‑Dimethyl tiazol‑2‑yl)‑2, 5 diphenyl tetrazolium bromide (MTT) was purchased from Sigma-Aldrich. Paroxetine pills (20 mg paroxetine in each pill) were purchased from Zhejiang Huahai Pharmaceutical Co., LTD (Zhejiang province, China). All other chemicals were of analytical grade as available.

Animals and cells

Extraction, isolation and purification of polysaccharides

Through hot water extraction and ethanol precipitation, crude polysaccharide designated PCWP was obtained with a yield of 0.39%. The extraction and purification steps were shown in Fig. 1. DEAE-52 cellulose (Cl form) was applied for further purification of the water eluent and 0.1 M NaCl eluent, respectively. Two polysaccharides designated PCWPW and PCWPS, with the yield about 13.45% and 12.01% from PCWP, were obtained.

Molecular weight and chemical compositions determination

Molecular weight, an important index of polysaccharide products, is closely

Discussion

Depression is a devastating disorder, afflicting up to 10% of the adult population in the United States and representing one of the leading causes of disability worldwide [37]. Although effective treatments are available, approximately one third of all patients with depression fail to respond to conventional antidepressant therapies [38]. Accordingly, there is a pressing need for new effective drug to develop better treatments. Inflammation is an important biological event that might increase

Conclusion

In this study, we obtained two homogenous water-soluble polysaccharides (PCWPW and PCWPS) and explored their structural features and biological activities. The molecular weights of PCWPW and PCWPS were 37,154 Da and 186,209 Da. PCWPW and PCWPS were mainly composed of different proportions of mannose, glucose, galactose and fucose. The TST and FST of chronic stress mice implied PCWPW and PCWPS possess obvious antidepressant effects on animal models. Neuroprotective activity study implicated that

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31800678 and 81703945), Science and Technology Innovation Fund of Shanxi Agricultural University (No. 2017YJ40), and Shanxi Province Research Award Foundation for Excellent Doctor (No. SXYBKY201729).

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