PMID: 

Acta Biochim Biophys Sin (Shanghai). 2020 Jan 17. Epub 2020 Jan 17. PMID: 31951250

Abstract Title: 

Cordycepin protects renal ischemia/reperfusion injury through regulating inflammation, apoptosis, and oxidative stress.

Abstract: 

Cordycepin (3'-deoxyadenosine) is a naturally occurring adenosine analog and one of the bioactive constituents isolated from Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. However, the actions of cordycepin against renal ischemia/reperfusion injury (I/R) are still unknown. In the present study, rats were subject to I/R and cordycepin was intragastrically administered for seven consecutive days before surgery to investigate the effects and mechanisms of cordycepin against renal I/R injury. The test results of kidney and peripheral blood samples of experimental animals showed that cordycepin significantly decreased serum blood urea nitrogen and creatinine levels and markedly attenuated cell injury. Mechanistic studies showed that cordycepin significantly regulated inflammation, apoptosis, and oxidative stress. These data provide new insights for investigating the natural product with the nephroprotective effect against I/R, which should be developed as a new therapeutic agent for the treatment of I/R in the future.

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PMID: 

Int J Biol Macromol. 2020 Jan 20 ;148:722-736. Epub 2020 Jan 20. PMID: 31972201

Abstract Title: 

Chemical structure and inhibition onα-glucosidase of the polysaccharides from Cordyceps militaris with different developmental stages.

Abstract: 

The natural form of wild edible fungus is the fruiting body. The cultivation of fruiting bodies from sexual reproduction requires strict conditions and long periods. Some literatures have paid attentions on the mycelia prepared with liquid fermentation to alter fruiting bodies. Cordyceps militaris (C. militaris) is a kind of precious edible fungus. The polysaccharide is an important active ingredient in C. militaris. The manuscript aimed to evaluate the feasibility of alternative of mycelia to fruit bodies with studies of polysaccharides from C. militaris of different developmental stages. The two polysaccharides were separated. The chemical structure and inhibitory activity onα-glucosidase of polysaccharides were explored. The results indicated that the structure and inhibitory activity on α-glucosidase of polysaccharides with different developmental stages had significant differences. The polysaccharides from fruiting bodies had better inhibitory activity on α-glucosidase. It demonstrated that the mycelia of C. militaris from asexual reproduction with liquid fermentation can't be an effective substitute for fruiting bodies from sexual reproduction, from the perspective of polysaccharides.

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PMID: 

Biomed Pharmacother. 2020 Jan 21 ;124:109834. Epub 2020 Jan 21. PMID: 31978767

Abstract Title: 

The protective effect of cordyceps sinensis extract on cerebral ischemic injury via modulating the mitochondrial respiratory chain and inhibiting the mitochondrial apoptotic pathway.

Abstract: 

Cerebral ischemia is a common refractory brain disease, resulting from a reduction in the blood flow to the brain. Mitochondrial dysfunction leads to ischemic stroke and brain injury. Cordyceps sinensis (CS) is an important traditional Chinese medicine, which has been linked to neuroprotection in recent studies. In this study, we investigated the role of the mitochondrial respiratory chain and the mitochondrial apoptotic pathway on the protective effect of Cordyceps sinensis extract (CSE) against cerebral ischemia injury both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) model, administration of CSE relieved neuronal morphological damage and attenuated the neuronal apoptosis. CSE also reduced neurobehavioral scores and oxygen free radical (OFR), while improving the levels of ATP, cytochrome c oxidase (COX), and mitochondrial complexes I-IV. Furthermore, the mRNA expression of Bax, cytochrome c (Cyt c) and caspase-3 were down-regulated. In brain microvascular endothelial cells (BMECs) exposed to oxygen and glucose deprivation (OGD), CSE prevented OGD-induced cellular apoptosis, and recovered the reduction of mitochondrial membrane potential (MMP). Moreover, CSE treatment induced an increase of Bcl-2 protein expression and a decrease of Bax, Cyt c and caspase-3 protein expression. Meanwhile, the caspase-3, -8, and -9 activities were also inhibited. The results indicate that CSE can relieve cerebral ischemia injury and exhibit protective effects via modulating the mitochondrial respiratory chain and inhibiting the mitochondrial apoptotic pathway.

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PMID: 

Oncol Lett. 2018 Mar ;15(3):3429-3436. Epub 2018 Jan 15. PMID: 29467867

Abstract Title: 

Low-molecular-weight polysaccharides fromMurrill modulate the Th1 response in cancer immunity.

Abstract: 

To assess the effect of low-molecular-weight polysaccharides fromMurrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4/CD8T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4/CD8T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression.

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PMID: 

Front Biosci (Elite Ed). 2019 01 1 ;11:12-19. Epub 2019 Jan 1. PMID: 30468634

Abstract Title: 

Antiapoptotic role of Agaricus blazei extract in rodent model of Parkinson's disease.

Abstract: 

Rotenone is a pesticide that has been shown to induce the pathological symptoms of Parkinson's disease (PD) in both cellular and animal models. In this study, we investigated the protective effect of Agaricus blazei extract on rotenone-induced dopaminergic degeneration and apoptosis in mice model. A.blazei extract blocked the rotenone-mediated diminution of   dopamine transporter (DAT)  and vesicular monoamine transporter 2 (VMAT 2) expression and  the downregulation of Bcl-2 and the upregulation of Bax, caspases-3, -6, -8 and caspase-9. Present data suggest that A. blazei extract plays acrucial role in regulation of proteins expression such as DAT and VMAT2 and pro-apoptotic and anti-apoptotic in Parkinsonism. In conclusion, the present study shows that A. blazei extract act as potential neuroprotective agent in the management of Parkinsonism.

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PMID: 

BMC Complement Altern Med. 2018 Dec 4 ;18(1):319. Epub 2018 Dec 4. PMID: 30514293

Abstract Title: 

Hot water extract of Agaricus blazei Murrill specifically inhibits growth and induces apoptosis in human pancreatic cancer cells.

Abstract: 

BACKGROUND: Pancreatic cancer is one of the most aggressive human malignancies. The development of a novel drug to treat pancreatic cancer is imperative, and it is thought that complementary and alternative medicine (CAM) could yield such a candidate. Agaricus blazei Murrill is a CAM that has been tested as an anticancer drug, but its efficacy against pancreatic cancer is poorly understood. To study the potential of A. blazei in the treatment of pancreatic cancer, we examined the effects of its hot water extract on the proliferation and global gene expression profile of human pancreatic cancer cells.METHODS: Three distinct human pancreatic cancer cell lines, MIAPaCa-2, PCI-35, and PK-8, and the immortalized human pancreatic duct-epithelial cell line, HPDE, were employed. The cells were incubated with the appropriate growth medium supplemented with the hot water extract of A. blazei at final concentrations of 0.005, 0.015%, or 0.045%, and cellular proliferation was assessed for five consecutive days using an MTT assay. Apoptosis was examined by using flow cytometry and the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Caspase-dependent apoptosis was assayed using immunoblotting. Global gene expression profiles were examined using a whole human genome 44 K microarray, and the microarray results were validated by using real-time reverse transcription PCR.RESULTS: The hot water extract of A. blazei significantly inhibited the proliferation of cultured pancreatic cancer cells through the induction of G0/G1 cell cycle arrest and caspase-dependent apoptosis; the effect was the smallest in HPDE cells. Furthermore, significant alterations in the global gene expression profiles of pancreatic cancer cells occurred following treatment with the hot water extract of A. blazei. Genes associated with kinetochore function, spindle formation, and centromere maintenance were particularly affected, as well as cyclins and cyclin-dependent kinases that are essential for cell cycle progression. In addition, proapoptotic genes were upregulated.CONCLUSIONS: The hot water extract of A. blazei may be useful for the treatment of pancreatic cancer and is a potential candidate for the isolation of novel, active compounds specific for mitotic spindle dysfunction.

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PMID: 

Int Immunopharmacol. 2019 Aug ;73:502-514. Epub 2019 Jun 4. PMID: 31173972

Abstract Title: 

Immunopathological effects of Agaricus blazei Murill polysaccharides against Schistosoma mansoni infection by Th1 and NK1 cells differentiation.

Abstract: 

In this study, we examined the ability of A. blazei Murill polysaccharides (AB-PS) to activate the immune system in vivo and the protective activity exhibited against parasitic S. mansoni in the murine model. AB-PS treatment significantly reduced the worm and egg burden in infected BALB/c and C57BL/6 mice with dose- and time-dependent manners. Additionally, a dose- and time-dependent expression of IL-2, INF-γ, and TNF-α cytokines was also observed in both strains of mice treatments. Using T1/T2 doubly transgenic mice, we demonstrated that AB-PS-treated mice splenocytes initiated early differentiation of Th1 and NK1 cells, which was consistent with the reduction course of Schistosoma infection. Although AB-PS treatment enhanced the Th1 response, it did not suppress Th2 cell activity in treated mice. Histopathological data of the livers showed AB-PS treatment significantly attenuated the liver fibrosis induced by S. mansoni eggs. AB-PS augmented type-1 responses by inducing Th1 and NK1 cell differentiation to effectively decrease the infection rate of S. mansoni. Furthermore, AB-PS treatment may not only inhibit the schistosome infection, but also improving the pathological effects of granulomas formation. This study provides evidence for a novel therapeutic potential, by which A. blazei Murill may be used to treat or prevent schistosome infection.

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PMID: 

Mutat Res. 2019 Sep ;845:403078. Epub 2019 Aug 1. PMID: 31561902

Abstract Title: 

Antigenotoxic and antioxidant potential of medicinal mushrooms (Immune Assist) against DNA damage induced by free radicals-an in vitro study.

Abstract: 

Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei – Cordyceps sinensis – Grifola frondosa – Ganoderma lucidum – Coriolus versicolor – Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against HOinduced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 μg/mL, while in posttreatment it was the concentration of 250 μg/mL. Kinetics of attenuation of HOinduced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60 min), reaching the greatest reduction after 15 and 45 min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNAdamage after 45 min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.

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PMID: 

Food Sci Nutr. 2020 Jan ;8(1):332-339. Epub 2019 Dec 5. PMID: 31993159

Abstract Title: 

Assessment of antioxidant and antidiabetic properties ofMurill extracts.

Abstract: 

Murill (ABM), a medicinal mushroom, has beneficial effects on various human metabolic diseases. The objective of this research was to evaluate the antioxidant and antidiabetic properties of ABM extracts (ethanol extract and ethyl acetate extract). The antioxidant activities of ABM ethanol extract (EE) and ethyl acetate extract (EA) were analyzed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radical scavenging assays and the reducing power using KFe(CN)in vitro. Moreover, the effects of EE and EA onα-glucosidase inhibitory activity and improving glucose uptake by HepG2 cells were investigated in vitro. The EA showed stronger antioxidant activity, as well as inhibition of α-glucosidase, compared to EE. The analysis of glucose uptake by HepG2 cells showed that EA had significant glucose-lowering activity and exhibited no difference compared to metformin. The results suggest that ABM extracts could improve the glucose uptake by HepG2 cells and thereby alleviate postprandial hyperglycemia. This investigation provides a strong rationale for further studies on the application of ABM to control type 2 diabetes.

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PMID: 

Food Funct. 2019 Jun 19 ;10(6):3758-3767. PMID: 31179460

Abstract Title: 

Water-soluble extracts from edible mushrooms (Agaricus bisporus) as inhibitors of hepatitis C viral replication.

Abstract: 

Hepatitis C virus (HCV) is the main agent responsible for chronic liver disease. Recent advances in anti-HCV treatment strategies have significantly increased the viral clearance rate (>90%). However, sustained antiviral responses vary in different cohorts, and high costs limit the broad use of direct-acting antivirals (DAAs). The goal of this study is to evaluate the inhibitory ability of well characterized (LC-QTOF-MS/MS) aqueous extracts obtained from edible mushrooms (Agaricus bisporus) to diminish HCV viral replication. Our data have demonstrated an in vitro inhibitory effect of A. bisporus extracts on NS3/4A protease and HCV replication. Fractionation by ultra-filtration and sequential liquid-liquid extraction showed that the compounds responsible for the inhibition are water-soluble with low molecular weights (

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