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As potential candidates for treating ulcerative colitis (UC), polysaccharides have been attracting extensive interest in recent years. Cordyceps sinensis ( C. sinensis ) is a kind of traditional Chinese edible food, and its polysaccharide fractions have been found to be effective in regulating immunity and protecting the kidneys. To determine the potential function of polysaccharides from natural C. sinensis on UC, their effects in terms of histological, serological, biochemical, and immunological aspects on dextran sulphate sodium (DSS)-induced colitis mice model were investigated. Results showed that the polysaccharides significantly alleviated colitis by increasing the colon length, alleviating colon tissue damage, and inhibiting the activation of the NF-κB pathway. In addition, polysaccharides reduced the contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum, increased the number of goblet cells, and improved the expression of intestinal tight junction proteins (Occludin and Claudin-1). They also evidently enhanced the formation of IgA-secretory cells and sIgA contents. Furthermore, the polysaccharides modulated the gut microbiota by decreasing the relative abundance of Bilophila and increasing the relative abundance of Dehalobacterium , Coprococcus , Oscillospira , and Desulfovibrio , which is accompanied by an increase in the short chain fatty acids' (SCFAs) concentrations in cecal contents. These results suggested that C . sinensis polysaccharides possessed promising intervening effects on experimental acute UC in mice.

A polysaccharide from Cordyceps sinensis (NCSP) was reported to attenuate intestinal injury and regulate the balance of T helper (Th)1/Th2 cells in immunosuppressed mice. However, whether it influences Th17 and regulatory T (Treg) cells as well as gut ecology remains unknown. In the present study, the intestinal injury mouse model was also established by intraperitoneal injection of cyclophosphamide (Cy) for three consecutive days. NCSP was found to increase the number of CD4 + T cells, stimulate the secretion of interleukins (IL)-17 and IL-21, and the expression of transcription factor (retinoic acid-related orphan receptor (ROR)-γt). The levels of transforming growth factor (TGF)-β3 and transcription factor (forkhead box (Fox)p-3) were increased in NCSP-treated groups. Moreover, NCSP upregulated the mRNA expression of toll like receptors (TLR-2, -6 and -9), while it downregulated the TLR-4 expression. In addition, NCSP modulated the intestinal microbiota composition and increased the levels of SCFAs. These findings indicated that NCSP may enhance intestinal immunity and have the potential to become a prebiotic to regulate intestinal microbiota.

Cordyceps sinensis is thought to have anti-cancer effects, but its mechanisms remain elusive. In this study, we aimed to investigate the anti-cancer effect of Cordyceps sinensis polysaccharide (CSP) on human colon cancer cell line (HCT116) and its mechanism. Results indicated that CSP significantly inhibited the proliferation of HCT116 cells, increased autophagy and apoptosis, while blocked autophagy flux and lysosome formation. Further experiments showed that CSP decreased the expression of PI3K and phosphorylation level of AKT and mTOR, increased the expression of AMPKa and phosphorylation level of ULK1. In addition, repression of CSP-induced autophagy by bafilomycin (autophagy inhibitor) enhanced apoptosis and cell death of HCT116 cells. Hence, our findings suggested that CSP inhibited the proliferation of HCT116 cells by inducing apoptosis and autophagy flux blockage, which might be achieved through PI3K-AKT-mTOR and AMPK-mTOR-ULK1 signaling. CSP may be a potential therapeutic agent for colon cancer., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The present study aimed to investigate the protective effect of cultured Cordyceps sinensis polysaccharides (CSP) on cyclophosphamide (Cy)-induced intestinal mucosal immunosuppression and microbial dysbiosis in mice. Results showed that CSP stimulated cytokines secretion (IL-12, IFN-γ, IL-4, IL-13, IL-6, IL-17, IL-10, TGF-β3, TNF-α, IL-2, IL-21) and transcription factors production (T-bet, GATA-3, RORγt, Foxp3). TLRs (TLR-2, TLR-4, TLR-6) and NF-κB pathway key proteins (p-IκB-α, NF-κB p65) were also upregulated after CSP administration. Moreover, CSP recovered SCFAs levels which decreased by Cy treatment. Furthermore, 16S rRNA sequencing of fecal samples was performed. α-diversity and β-diversity analysis revealed CSP improved microbial community diversity and modulated the overall structure of gut microbiota. Taxonomic composition analysis found that CSP increased the abundance of probiotics (Lactobacillus, Bifidobacterium, Bacteroides) and decreased pathogenic bacteria (Clostridium, Flexispira). These findings suggested the potential of CSP as a prebiotics to reduce side effects of Cy on intestinal mucosal immunity and gut microbiota., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Water-soluble β-d-glucan was obtained from wild Cordyceps sinensis by alkali solution and ethanol precipitation. The structure characteristics were determined using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD), methylation combined with gas chromatography-mass spectrometry, and one-/two-dimensional nuclear magnetic resonance spectroscopy. Results showed that β-d-glucan had a structure of every seven (1→3)-β-d-Glc p backbone residues with two (1→6)-β-d-Glc p branches. Additionally, conformation properties in different solvents were investigated by static light scattering, dynamic light scattering, and HPSEC with multiple detectors. It was found that β-d-glucan in 0.5 M NaOH had a narrow unimodal distribution of hydrodynamic radius displaying a spherical coil conformation, whereas it formed severe aggregation in dimethyl sulfoxide. In 0.1 M NaNO 3 , β-d-glucan mainly existed as a rod-like conformation corresponding to a helical structure together with small aggregates (10%). This work added more information to the understanding of C. sinensis polysaccharides.

Abstract Polysaccharide is one of the main bioactive substances in Cordyceps sinensis (C. sinensis). The aim of this study was to investigate the effect of polysaccharide from natural C. sinensis (CSP) on intestinal mucosal immunity and antioxidant activity in cyclophosphamide (Cy)-induced intestinal immunosuppressed mice, further to explore the potential mechanism. Results showed that in mice with Cy-induced intestinal injury, the supplement of CSP (25, 50, 100 mg/kg·bw) significantly increased the levels of goblet cells and mucus in intestine in a dose-dependent manner. The formation of immunoglobulin A (IgA)-secreting cells and the secretory IgA (sIgA) contents were promoted obviously in CSP groups. Furthermore, CSP significantly promoted the secretion or mRNA expression of T helper (Th) 1 style cytokines, including interleukin-2 (IL-2), IL-12 p40, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), in addition to Th1 style transcription factor T-bet. Besides, the levels of Th2 style cytokines, including IL-4, IL-10 and transcription factor GATA-3, were also improved. The value of T-bet/GATA-3, as well as IFN-γ/IL-4 was increased obviously. These results indicated that CSP effectively enhanced intestinal mucosal immunity and regulated polarization of Th1/Th2 cells. The total antioxidant capacity (T-AOC), and the activities of superoxidase dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in liver were increased significantly, and the content of malondialdehyde (MDA) was decreased dose-dependently. In conclusion, CSP effectively ameliorated Cy-induced intestinal injury in mice, which provided a good suggestion of the potential utilization of CSP as a natural immunopotentiator and antioxidant. Graphical abstract Image 1 Highlights • CSP provided protection against intestinal mucosal injury induced by Cy. • CSP enhanced intestinal mucosal immunity in intestinal immunosuppressed mice. • CSP regulated Th1/Th2 balance disrupted by Cy. • CSP improved antioxidant status in immunosuppressed mice. [ABSTRACT FROM AUTHOR]

A water-soluble polysaccharide, named NCSP-50, was obtained from natural Cordyceps sinensis by hot water extraction and ethanol fractionation precipitation. It was eluted as a single symmetrical peak and had an average molecular weight of 9.76 × 10 5 Da. The structure was determined by monosaccharide composition, methylation analysis, 1D/2D NMR spectroscopy, and enzymatic hydrolysis and characterization of the oligosaccharides by MALDI-TOF mass spectrometry. The repeating unit of this polysaccharide was proposed as follows: Image 2 This glucan showed potent immunostimulatory activity on the basis of its significant abilities to promote macrophage proliferation, enhance NO production, as well as and cytokines (IL-1β and TNF-α) secretion. [ABSTRACT FROM AUTHOR]

This study investigates the chemical composition and bioactive components of three natural Cordyceps sinensis and one culture mycelium, and further compares the antioxidant properties of their aqueous extracts. The contents of crude fat and total amino acids were significantly higher in cultured sample. Glutamic acid was the most abundant amino acid in all samples; arginine was the second major amino acid in natural samples, while in cultured sample it contained large quantity of aspartic acid and leucine. The contents of minerals, except for Cr, Mo, Sn, V and Cd, were significantly different between natural and cultured samples. The content of mannitol in natural samples was significantly higher, ranging from 9.85% to 11.51%, while in the mycelium the value was less than half. On the contrary, the levels of polysaccharide, adenine and adenosine in cultured sample amounted to 10.43%, 0.50 mg/g and 2.61 mg/g, respectively, considerably higher than the natural ones. There was no difference in content of guanosine among four samples. Cordycepin was not detected in the four samples examined. Additionally, in vitro antioxidant activity evaluations showed that water extracts of cultured sample had a stronger ability in scavenging DPPH and hydroxyl radicals, as well as a higher reducing power. [ABSTRACT FROM AUTHOR]