Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLR(+/-) hamsters.

BACKGROUND: Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. METHODS: After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 µg/mL) on inhibiting adipocyte differentiation was investigated in vitro. RESULTS: CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR(+/-) hamsters, which have a human-like lipid profile. After 5 months' administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation. CONCLUSIONS: The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention.

Recent Advances on Bioactive Ingredients of Morchella esculenta.

Morchella esculenta (M. esculenta) is a delicious edible mushroom prized for its special flavor and strong health promoting abilities. Several bioactive ingredients including polysaccharides, polyphenolic compounds, proteins, and protein hydrolysates all contribute to the biological activities of M. esculenta. Different polysaccharides could be extracted and purified depending on the extraction methods and M. esculenta studied. Monosaccharide composition of M. esculenta polysaccharides (MEP) generally includes mannose, galactose, and glucose, etc. MEP possess multiple bioactivities such as antioxidant, anti-inflammation, immunoregulation, hypoglycemic activity, atherosclerosis prevention and antitumor ability. Other components like polyphenols, protein hydrolysates, and several crude extracts are also reported with strong bioactivities. In terms of potential applications of M. esculenta and its metabolites as nutritional supplements and drug supplements, this review aims to comprehensively summarize the structural characteristics, biological activities, research progress, and research trends of the active ingredients produced by M. esculenta. Among the various biological activities, the substances extracted from both natural collected and submerged fermented M. esculenta are promising for antioxidants, immunomodulation, anti-cancer and anti-inflammatory applications. However, further researches on the extraction conditions and chemical structure of bioactive compounds produced by M. esculenta still need investigations.

Yeast Shells Encapsulating Adjuvant AS04 as an Antigen Delivery System for a Novel Vaccine against Toxoplasma Gondii.

Toxoplasma gondii (T. gondii) infection causes severe zoonotic toxoplasmosis, which threatens the safety of almost one-third of the human population globally. However, there is no effective protective vaccine against human toxoplasmosis. This necessitates anti-T. gondii vaccine development, which is a main priority of public health. In this study, we optimized the adjuvant system 04 (AS04), a vaccine adjuvant constituted by 3-O-desacyl-4'-monophosphoryl lipid A (a TLR4 agonist) and aluminum salts, by packing it within natural extracts of ß-glucan particles (GPs) from Saccharomyces cerevisiae to form a GP-AS04 hybrid adjuvant system. Through a simple mixing procedure, we loaded GP-AS04 particles with the total extract (TE) of T. gondii lysate, forming a novel anti-T. gondii vaccine GP-AS04-TE. Results indicated that the hybrid adjuvant can efficiently and stably load antigens, mediate antigen delivery, facilitate the dendritic uptake of antigens, boost dendritic cell maturation and stimulation, and increase the secretion of pro-inflammatory cytokines. In the mouse inoculation model, GP-AS04-TE significantly stimulated the function of dendritic cells, induced a very strong TE-specific humoral and cellular immune response, and finally showed a strong and effective protection against toxoplasma chronic and acute infections. This work proves the potential of GP-AS04 for exploitation as a vaccine against a range of pathogens.

Edible fungal polysaccharides, the gut microbiota, and host health.

The plasticity of the gut microbiota (GM) creates an opportunity to reshape the biological output of gut microbes by manipulating external factors. It is well known that edible fungal polysaccharides (EFPs) can reach the distal intestine and be assimilated to reshape the GM. The GM has unique devices that utilize various EFPs and produce oligosaccharides, which can selectively promote the growth of beneficial bacteria and are fermented into short-chain fatty acids that interact closely with intestinal cells. Here we review EFPs-based interventions for the GM, particularly the key microorganisms, functions, and metabolites. In addition, we discuss the bi-directional causality between GM imbalance and diseases, and the beneficial effects of EFPs on host health via GM. This review can offer a valuable reference for the design of edible fungal polysaccharide- or oligosaccharide-based nutrition interventions or drug development for maintaining human health by targeted regulation of the GM.

Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn's disease.

The Saccharomyces cerevisiae CNCM I-3856 was previously reported to strongly inhibit adherent-invasive Escherichia coli (AIEC) adhesion to intestinal epithelial cells in vitro and to favor AIEC elimination from the gut in a murine model of Crohn's disease in vivo. In order to identify which cell wall components of yeast are responsible for AIEC elimination, constituent polysaccharides of yeast were isolated and their anti-adhesive ability against AIEC adhesion in vitro was screened. A fraction containing mannan, ß-glucan and α-glucan extracted from yeast cell-walls was shown to inhibit 95% of AIEC adhesion in vitro and was thus identified as the strongest anti-adhesive yeast cell wall component. Furthermore, this mannan-glucan-containing fraction was shown to accelerate AIEC decolonization from gut in vivo. This fraction could be proposed as a treatment to eliminate AIEC bacteria in patients with Crohn's disease, a microbial trigger of intestinal inflammation.

New insights into the anti- hepatoma mechanism of triple-helix ß- glucan by metabolomics profiling.

Natural polysaccharide as the third abundant biomacromolecule has attracted considerable attentions due to their superior anti-tumor activities. However, the anti-tumor mechanism of polysaccharides has not been completely understood. Herein, the anti-tumor effects of black fungus polysaccharide (BFP), a typical ß-glucan was comprehensively investigated, and the anti-tumor mechanism was obtained from metabolomics profiling. The in vitro results demonstrate that BFP inhibited the proliferation, migration and invasion of hepatoma carcinoma cells (HCC) through inducing the cell apoptosis and arresting the cell cycle at S phase without direct cytotoxicity. The hepatoma-bearing nude mice experiments further demonstrate that BFP could significantly inhibit the growth without system toxicity in vivo. Mass spectrometry-based metabolomics unveils that BFP significantly disturbed the multiple metabolic pathways, leading to the inhibition of tumor cells proliferation by promoting DNA damage, attenuating DNA damage repair, and inhibiting DNA synthesis. This study provides new insights for pharmacological research and clinical practice of polysaccharides.

Nutraceutical Approach to Preventing Coronavirus Disease 2019 and Related Complications.

Introduction: Several months ago, Chinese authorities identified an atypical pneumonia in Wuhan city, province of Hubei (China) caused by a novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19". Evidence Acquisition: Several approaches are currently underway for the treatment of this disease, but a specific cure remains to be established. Evidence Synthesis: This review will describe how the use of selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients. Conclusions: Even if a specific and effective cure for COVID-19 still has some way to go, selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients.

Chemical structure and anti-inflammatory activity of a branched polysaccharide isolated from Phellinus baumii.

Phellinus baumii is used to treat inflammatory bowel disease (IBD) and gastroenteritis. In this study, a 46 kDa heteropolysaccharide SHPS-1 was isolated from fruiting bodies of P. baumii. SHPS-1 consisted of arabinose, mannose, glucose, and galactose at a molar ratio of 2.2:15.7:49.3:32.8. SHPS-1 had a backbone containing 1,3-linked ß-D-Glcp and 1,6-linked α-D-Galp residues, and Araf, Manp and Galp units were attached as oligosaccharidic side chains to the backbone at C-6 of some glucopyranoses. SHPS-1 decreased phosphorylation level of STAT-1 and expression levels of STAT-1 targeted genes such as iNOS and TNF-α in lipopolysaccharide-stimulated macrophage RAW 264.7 cells. Furthermore, SHPS-1 promoted the expression of IL-10 and macrophage mannose receptor CD 206, markers of tissue repairing macrophages. SHPS-1 alleviated ulcerative colitis in mice by decreasing pro-inflammatory genes and increasing anti-inflammatory and tissue repairing genes. Collectively, SHPS-1 polysaccharide from P. baumii had anti-inflammatory activity and can potentially treat IBD.

Fabrication and characterization of Rhizochitosan and its incorporation with platelet concentrates to promote wound healing.

Composite dressing composed of Rhizochitosan and Regenplex™ to promote wound healing were assessed. Rhizochitosan was fabricated by deacetylation of Rhizochitin, which obtained by simply depigmenting sporangium-free mycelial mattress produced from Rhizopus stolonifer F6. Physicochemical characterizations of Rhizochitosan demonstrated that it contained 13.5% chitosan with a water-absorption ability of 35-fold dry weight and exhibiting hydrogel nature after hydration. In a wound-healing study on SD rats with full-thickness injury, the composite dressing had a better healing effect than those for each individual components and control group and wound even healed as functional tissue instead of scar tissue. The underlying mechanism of the composite beneficial to wound remodeling is likely attributable to a more reduction level of matrix metalloproteinase (MMP)-9 expression in early stage and a higher MMP-2 expression level in a later stage of healing process. Conclusively, the composite dressing demonstrated to be highly beneficial to the healing of full-thickness injury wound.

Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon.

This study investigated the effects of water-soluble polysaccharide extracted from the sporoderm-removed spores of Ganoderma lucidum (GLP) against AOM/DSS-induced inflammation, tumorigenesis, and gut microbiota modification, which has never been reported before. Our data revealed that GLP (200 and 300 mg/kg) decreased AOM/DSS-induced colitis and tumorigenesis, manifested by significantly reduced disease activity index score, and total number and size of tumors. Furthermore, GLP ameliorated AOM/DSS-induced microbiota dysbiosis, increased short-chain fatty acid production, and alleviated endotoxemia by inhibiting TLR4/MyD88/NF-κB signaling. Besides, GLP profoundly improved gut barrier function as evidenced by increased numbers of goblet cells, MUC2 secretion, and tight junction protein expressions. GLP treatment inhibited macrophage infiltration and downregulated IL-1ß, iNOS, and COX-2 expressions. Additionally, GLP inhibited lipopolysaccharides (LPS)-induced inflammation markers and MAPK (JNK and ERK) activation in macrophage RAW264.7, intestinal HT-29, and NCM460 cells. In conclusion, these results indicate that GLP is a promising prebiotic for the treatment of colorectal cancer.

Classification, structure and mechanism of antiviral polysaccharides derived from edible and medicinal fungus.

The deficiency of chemical-synthesized antiviral drugs when applied in clinical therapy, such as drug resistance, and the lack of effective antiviral drugs to treat some newly emerging virus infections, such as COVID-19, promote the demand of novelty and safety anti-virus drug candidate from natural functional ingredient. Numerous studies have shown that some polysaccharides sourcing from edible and medicinal fungus (EMFs) exert direct or indirect anti-viral capacities. However, the internal connection of fungus type, polysaccharides structural characteristics, action mechanism was still unclear. Herein, our review focus on the two aspects, on the one hand, we discussed the type of anti-viral EMFs and the structural characteristics of polysaccharides to clarify the structure-activity relationship, on the other hand, the directly or indirectly antiviral mechanism of EMFs polysaccharides, including virus function suppression, immune-modulatory activity, anti-inflammatory activity, regulation of population balance of gut microbiota have been concluded to provide a comprehensive theory basis for better clinical utilization of EMFs polysaccharides as anti-viral agents.

Poria cocos polysaccharide attenuates damage of nervus in Alzheimer's disease rat model induced by D-galactose and aluminum trichloride.

Poria cocos polysaccharide (PCP) is a compound from Poria cocos, and which is used as a classical tonic agent. This article aims to investigate the effects of PCP on neuronal damage of hippocampus and cognitive function in a rat model of Alzheimer's disease induced by D-galactose and aluminum trichloride. Oxiracetam (ORC) was used as a positive drug in this experiment. The rats were treated with PCP at doses of 100, 200 and 300 mg/kg/day for 30 days and ORC at dose of 346 mg/kg/day after modeling. The results of behavioral test showed that PCP could prevent cognitive decline in Alzheimer's disease rats as assessed by Y-maze test and Morris water maze test. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with PCP. Moreover, PCP could reduce neuronal apoptosis in hippocampus of Alzheimer's disease rats. Furthermore, the activities of superoxide dismutase in the hippocampus were elevated by PCP administration, while acetyl cholinesterase, reactive oxygen, malondialdehyde and inflammatory factors levels were reduced. In addition, we found PCP could attenuate MAPK/NF-κB signal pathway in the hippocampus. All results illustrated that PCP could exert neuroprotective effects at least partly through alleviating oxidative stress, apoptosis, inflammation and inhibiting the MAPK/NF-κB pathway in Alzheimer's disease rats induced by D-galactose and aluminum trichloride.

Structural characterization and amelioration of sulfated polysaccharides from Ganoderma applanatum residue against CCl4-induced hepatotoxicity.

Natural polysaccharides and their derivatives have attracted academic attention due to their extensive physiological activities. However, the hepatoprotective effects against carbon tetrachloride (CCl4) toxicity have not been well elucidated. The objectives of this study were to characterize the structural properties of sulfated Ganoderma applanatum residue polysaccharides (SGRP) and to evaluate their inhibitory effects on liver fibrosis caused by oxidative stress and inflammation. Our in vivo study showed that SGRP was hepatoprotective in CCl4-induced chronic liver injury mice. It reduced the histopathological damages, down-regulated CYP2E1 (cytochrome P450 2E1) expression, reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, improved the anti-oxidative and anti-inflammatory properties, inhibited TLR4/NF-κB signaling pathway, and reduced the release of inflammatory cytokines. The structural studies indicated that SGRP is a heteropolysaccharide with 7.8% sulfur content and α-linked residue. Our study projects SGRP as a potential candidate in anti-fibrosis treatment by using it as a food supplement or in medicines produced by pharmaceutical industries.

A review on the production, structure, bioactivities and applications of Tremella polysaccharides.

Tremella polysaccharide is known to be structurally unique and biologically active natural products, abundant and versatile in activities and applications in food industry, daily chemical industry and medicine industry. In order to improve the industrialisation of Tremella polysaccharide, the limitations of preparation and structure-activity relationship of Tremella polysaccharide were reviewed in this paper. The research progress of Tremella polysaccharide in the past 20 years was summarized from the sources, preparation methods, molecular structure, activity and application, and the research trend in the future was also prospected. The application prospect of Tremella polysaccharide in against multiple sub-health states was worth expecting.

Recent findings on the role of fungal products in the treatment of cancer

In modern medicine, natural products have aided humans against their battles with cancer. Among these products, microorganisms, medicinal herbs and marine organisms are considered to be of great benefit. In recent decades, more than 30 fungal immunity proteins have been identified and proved to be extractable from a wide range of fungi, including mushrooms. Although chemotherapy is used to overcome cancer cells, the side effects of this method are of great concern in clinical practice. Fungal products and their derivatives constitute more than 50% of the clinical drugs currently being used globally. Approximately 60% of the clinically approved drugs for cancer treatment have natural roots. Anti-tumor immunotherapy is prospective with a rapidly growing market worldwide due to its high efficiency, immunity, and profit. Polysaccharide extracts from natural sources are being used in clinical and therapeutic trials on cancer patients. This review aims to present the latest findings in cancer treatment through isolated and extraction of fungal derivatives and other natural biomaterials (AU)

Medicinal Properties and Bioactive Compounds from Wild Mushrooms Native to North America.

Mushrooms, the fruiting bodies of fungi, are known for a long time in different cultures around the world to possess medicinal properties and are used to treat various human diseases. Mushrooms that are parts of traditional medicine in Asia had been extensively studied and this has led to identification of their bioactive ingredients. North America, while home to one of the world's largest and diverse ecological systems, has not subjected its natural resources especially its diverse array of mushroom species for bioprospecting purposes: Are mushrooms native to North America a good source for drug discovery? In this review, we compile all the published studies up to September 2020 on the bioprospecting of North American mushrooms. Out of the 79 species that have been investigated for medicinal properties, 48 species (60%) have bioactivities that have not been previously reported. For a mere 16 selected species, 17 new bioactive compounds (10 small molecules, six polysaccharides and one protein) have already been isolated. The results from our literature search suggest that mushrooms native to North America are indeed a good source for drug discovery.

Promising Anti-cancer Therapeutics From Mushrooms: Current Findings and Future Perceptions.

BACKGROUND: Nowadays, medicines derived from natural sources have drawn much attention as potential therapeutic agents in the suppression and treatment of cancer because of their low toxicity and fewer side effects. OBJECTIVE: The present review aims to assess the currently available knowledge on the ethnomedicinal uses and pharmacological activities of bioactive compounds obtained from medicinal mushrooms towards cancer treatment. METHODS: A literature search has been conducted for the collection of research papers from universally accepted scientific databases. These research papers and published book chapters were scrutinized to retrieve information on ethnomedicinal uses of mushrooms, different factors involved in cancer cell proliferation, clinical and in silico pharmaceutical studies made for possible treatments of cancer using mushroom derived compounds. Overall, 241 articles were retrieved and reviewed from the year 1970 to 2020, out of which 98 relevant articles were finally considered for the preparation of this review. RESULTS: This review presents an update on the natural bioactive substances derived from medicinal mushrooms and their role in inhibiting the factors responsible for cancer cell proliferation. Along with it, the present review also provides information on the ethnomedicinal uses, solvents used for extraction of anti-cancer metabolites, clinical trials, and in silico studies that were undertaken towards anticancer drug development from medicinal mushrooms. CONCLUSION: The present review provides extensive knowledge on various anti-cancer substances obtained from medicinal mushrooms, their biological actions, and in silico drug designing approaches, which could form a basis for the development of natural anti-cancer therapeutics.

Recent findings on the role of fungal products in the treatment of cancer.

In modern medicine, natural products have aided humans against their battles with cancer. Among these products, microorganisms, medicinal herbs and marine organisms are considered to be of great benefit. In recent decades, more than 30 fungal immunity proteins have been identified and proved to be extractable from a wide range of fungi, including mushrooms. Although chemotherapy is used to overcome cancer cells, the side effects of this method are of great concern in clinical practice. Fungal products and their derivatives constitute more than 50% of the clinical drugs currently being used globally. Approximately 60% of the clinically approved drugs for cancer treatment have natural roots. Anti-tumor immunotherapy is prospective with a rapidly growing market worldwide due to its high efficiency, immunity, and profit. Polysaccharide extracts from natural sources are being used in clinical and therapeutic trials on cancer patients. This review aims to present the latest findings in cancer treatment through isolated and extraction of fungal derivatives and other natural biomaterials.

Antioxidation, anti-hyperlipidaemia and hepatoprotection of polysaccharides from Auricularia auricular residue.

As hyperlipidemia was a pathological progress by lipid dysfunctions, the present object was to investigate the hypolipidemic and hepatoprotective effects of Auricularia auricular residue polysaccharides (RPS) against HFE (high-fat emulsion) toxicities in mice. The structure analysis showed that the RPS was pyranose-polysaccharides mainly composed of glucose with the weight-average molecular weight of 2.00 × 105 Da. The in vivo experiments demonstrated that the RPS had potential hepatoprotections by enhancing the antioxidant and anti-hyperlipidaemia status, and could inhibit the increasing body weights. Besides, the RPS could improve the glucose utilization with the oral glucose tolerance test (120 min) of 5.04 ± 0.12 mmol/L at the dose of 400 mg/kg bw. The results in present study demonstrated that RPS could be used as a functional foods and natural medicines against the HFE-induced hyperlipidemia and its complications.

Amelioration of the Lipogenesis, Oxidative Stress and Apoptosis of Hepatocytes by a Novel Proteoglycan from Ganoderma lucidum.

The steatosis and resultant oxidative stress and apoptosis play the important roles in the progression of nonalcoholic fatty liver disease (NAFLD), therefore, searching for the effective drugs against NAFLD has been a hot topic. In this work, we investigated a hyperbranched proteoglycan, namely FYGL extracted from Ganoderma lucidum, inhibiting the palmitic acid (PA)-induced steatosis in HepG2 hepatocytes. FYGL compose of hydrophilic polysaccharide and lipophilic protein. Both moieties conclude the reductive residues, such as glucose and cystine, making FYGL capable of anti-oxidation. Herein, we demonstrated that FYGL can significantly inhibit the steatosis, i.e., decrease the contents of triglycerides (TG) and total cholesterol (TC) in hepatic cells on the mechanism of increasing the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), therefore inhibiting the expressions of sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN), furthermore leading to the carnitine palmitoyl transferase-1 (CPT-1) expression increased against steatosis induced by fatty acids oxidation. Meanwhile, FYGL can alleviate reactive oxygen species (ROS) and malondialdehyde (MDA), promote superoxide dismutase (SOD) and total antioxidant capacity (T-AOC). Moreover, FYGL can prevent the cells from apoptosis by regulating the apoptosis-related protein expressions and alleviating oxidative stress. Notably, FYGL could significantly recover the cells activity and inhibit lactate dehydrogenase (LDH) release which were negatively induced by high concentration PA. These results demonstrated that FYGL has the potential functions to prevent the hepatocytes from lipid accumulation, oxidative stress and apoptosis, therefore against NAFLD.