PMID: 

Evid Based Complement Alternat Med. 2018 ;2018:9419264. Epub 2018 Mar 15. PMID: 29736181

Abstract Title: 

Improvement of Learning and Memory Induced byPolypeptide Treatment and the Underlying Mechanism.

Abstract: 

Our previous research revealed thatcan improve the learning and memory, and although the main active ingredient should be its polypeptide complexes, the underlying mechanism of its activity remains poorly understood. In this study, we explored the mechanisms by whichimproves learning and memory in a mouse model. Mice were given scopolamine hydrobromide intraperitoneally to establish a mouse model of learning and memory impairment. The effects ofpolypeptide in this model were tested using the Morris water maze test; serum superoxide dismutase activity; serum malondialdehyde levels; activities of acetyl cholinesterase, Na+-k+-ATPase, and nitric oxide synthase; and gamma aminobutyric acid and glutamate contents in brain tissue. Moreover, differentially expressed genes and the related cellular signaling pathways were screened using an mRNA expression profile chip. The results showed that the genes,, andwere involved in the effects ofpolypeptide on the nervous system of these mice. Our findings suggest thatpolypeptide may improve learning and memory in the scopolamine-induced mouse model of learning and memory impairment by scavenging oxygen free radicals, preventing oxidative damage, and protecting the nervous system.

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PMID: 

Am J Transl Res. 2018 ;10(3):857-865. Epub 2018 Mar 15. PMID: 29636875

Abstract Title: 

may inhibit Th22 cell chemotaxis to improve kidney function in lgA nephropathy.

Abstract: 

IgA nephropathy is the most common form of primary glomerulonephritis and an important cause of kidney failure. Cordyceps sinensis (CS) is a parasitic fungus that has a long history of use in Chinese medicine for the treatment of nephritis. Interleukin (IL)-22-producing helper T cells (Th22 cells) have been reported to be involved in lgA nephropathy. Th22 cells link the immune response to tissue inflammation. To elucidate the possible efficacy and mechanisms by which CS counteracts nephritis, we established an IgA nephropathy model in 6-week-old female BALB/c mice. The mice were randomly separated into 3 groups, the normal control, IgA nephropathy and CS (5 mg/kg/d) treatment groups. The Th22 cell frequencies and the relative pathological and cytokine changes were measured with flow cytometry, whereas the serum chemokine ligand 27 (CCL27) and IL-22 concentrations were detected with ELISA. The Th22 cell frequency decreased after 1 month of CS therapy. Additionally, mesangial cell proliferation decreased. Moreover, the chemokine receptor type 10 (CCR10), CCL27 and IL-22 expression levels were significantly reduced. In conclusion, CS may modulate the chemotaxis of Th22 cells to suppress inflammatory responses in IgA nephropathy.

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PMID: 

Food Chem Toxicol. 2018 Sep ;119:66-72. Epub 2018 May 16. PMID: 29753871

Abstract Title: 

Combinatorial usage of fungal polysaccharides from Cordyceps sinensis and Ganoderma atrum ameliorate drug-induced liver injury in mice.

Abstract: 

This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response. Relatively, through activation of peroxisome proliferator-activated receptorα (PPARα), PSG increased hepatic glutathione peroxidase and glutathione content depleted by CTX, as well as prevented mitochondria-dependent apoptosis with regulation on Bcl-2 family proteins (Bad, Bax and Bcl-2). In addition, protective effect of CFP was associated with enhanced modulations on cellular oxidant/antioxidant imbalance, mitochondrial apoptotic pathway and pro-inflammatory factors via PPARα upregulation and TLR9 downregulation. Taking together, the combinatorial approach based on CSP and PSG presented a practical option for the management of drug-induced liver injury.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 2018 May ;43(10):2134-2139. PMID: 29933683

Abstract Title: 

[Effects of cultivated Cordyceps sinensis on proliferation and apoptosis of human leukemia K562 cells].

Abstract: 

The present study was designed to investigate the effect of cultivated Cordyceps sinensis (CCS) on leukemia-derived K562 cells, and further explore the underlying mechanisms. After routine culture of K562 cells, MTT assay was used to detect the effect of CCS on survivel of human leukemia cell lines K562;DAPI staining was used to observe the morphological changes of the nucleus and AO/EB staining was used to observe cell apoptosis. JC-1 staining was employed to detect the changes in mitochondrial membrane potential. Flow cytometry (FCM) was used to detect cell cycle distribution, and Western blot analysis was used to detect the expression levels of Bax, Bcl-2, caspase 3, caspase 8, cyclin D1, CDK2, and CDK4 in K562 cells. The results showed that CCS (0.345-5.524 g·L⁻¹) substantially suppressed proliferation of K562 cells and induced G₁/S phase arrest in a dose-dependent manner. DAPI and AO/EB staining indicated that cell apoptosis was significantly induced by CCS treatment, accompanied by decreased mitochondrial membrane potential demonstrated by JC-1staining. Western blot results showed that CCS significantly increased the expression of Bax and, meanwhile, decreased the expression levels of Bcl-2, cyclin D1, CDK2, CDK4, caspase 3 and caspase 8. Collectively, our data demonstrated that CCS dose-dependently suppressed cell proliferation and induced cell apoptosis in K562 cells, and the mechanism might be associated with inducing cell cycle arrest, regulating Bcl-2/Bax ratio and activating the mitochondrial apoptosis pathway.

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PMID: 

Mol Med Rep. 2018 Sep ;18(3):3229-3241. Epub 2018 Jul 24. PMID: 30066944

Abstract Title: 

Effect of fermented Cordyceps sinensis on doxorubicin‑induced cardiotoxicity in rats.

Abstract: 

Cordyceps sinensis (CS) is a prominent medicinal herb in traditional Chinese medicine, and fermented CS is frequently used as a substitute for natural CS. Doxorubicin (DOX), an antitumor drug used in chemotherapy, is limited by its poor cardiotoxicity. The aim of the present study was to evaluate the protective effect of fermented CS against DOX‑induced cardiotoxicity and the potential underlying mechanisms. Male Sprague‑Dawley rats (180‑200 g) were randomly assigned to seven different treatment groups: Normal control, DOX control, DOX+captopril (0.05 g/kg), 0.75, 1.5 and 3 g/kg DOX+CS, and the CS (1.5 g/kg) control. Histopathological changes, cardiac energy metabolism, cyclic adenosine monophosphate (cAMP) signaling and the associated mRNA expression of AMP‑activated protein kinase (AMPK) were then evaluated. Fermented CS decreased the left ventricular weight index, heart weight index and mortality; however, it increased diastolic blood pressure and mean arterial pressure. In addition, it shortened the duration of the QRS complex and Sα‑T segment, decreased serum creatine kinase (CK) and aspartate aminotransferase activity, inhibited histopathological changes and reduced brain natriuretic peptide content. Treatment with fermented CS also increased the activities of superoxide dismutase and glutathione peroxidase, reduced malondialdehyde content, increased the mitochondrial activities of Na+K+‑adenosine 5'‑triphosphate (ATP) ase, Ca2+Mg2+‑ATPase and CK, and increased the creatine phosphate/ATP ratio and AMP/ATP ratio. Furthermore, it decreased the ATP/adenosine 5'‑diphosphate (ADP) ratio, upregulated AMPKα2 expression, reduced the activity of serum phosphodiesterases (PDEs) and increased myocardial cAMP content. The results of the present study demonstrated that fermented CS attenuated DOX‑induced cardiotoxicity by inhibiting myocardial hypertrophy and myocardial damage, ameliorating systolic function and the antioxidant enzyme system, improving cardiac energy metabolism, depressing the activities of PDEs, and by upregulating the cAMP and AMPK signaling pathways. Thus, fermented CS may be a candidate for the prevention of DOX‑induced cardiotoxicity, cardiac energy impairment and against a number of cardiac diseases.

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PMID: 

Saudi J Biol Sci. 2018 Jul ;25(5):991-995. Epub 2018 May 14. PMID: 30108453

Abstract Title: 

Anti-tumor and anti-metastatic roles of cordycepin, one bioactive compound of.

Abstract: 

Public interest in complementary and alternative medicine has been increased worldwide, due to its wide applications in cancer prevention and treatment. Cordycepin is one of the most common and crucial types of complementary and alternative medicine. Cordycepin (3'-deoxyadenosine), a derivative of adenosine, was first isolated from medicine drug. Cordycepin has been widely used as one compound for antitumor, which has been found to exert antiangiogenic, anti-metastatic, and antiproliferative effects, as well as inducing apoptosis. However, the mechanism of its anti-tumor activity is not well known. This review will clarify anti-tumor mechanisms of Cordycepin, which regulate signaling pathways related with tumor growth and metastasis. Cordycepin inhibit tumor growth via upregulating tumor apoptosis, inducing cell cycle arrest and targeting cancer stem cells (CSCs). Cordycepin regulates tumor microenvironment via suppressing tumor metastasis-related pathways. Thus, Cordycepins may be one of important supplement or substitute medicine drug for cancer treatment.

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PMID: 

Int J Mol Sci. 2018 Nov 7 ;19(11). Epub 2018 Nov 7. PMID: 30405049

Abstract Title: 

-FermentedInhibits Inflammatory Reactions and Alleviates Contact Dermatitis.

Abstract: 

is a medicinal mushroom used to treat immune-related diseases in East Asia. We investigated the anti-inflammatory effect of the extract ofgrown on germinated(GRC) fermented withON89A isolated from onion (GRC-ON89A) in vivo as well as in vitro. The anti-inflammatory effect of GRC-ON89A was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The total polyphenol content (TPC) and total flavonoid content (TFC) in the GRC-ON89A ethanol extract were significantly increased compared to that in GRC. GRC-ON89A hexane fraction (GRC-ON89A-Hex) inhibited the release of nitric oxide (NO) compared to that of the LPS-treated control without cytotoxicity in LPS-stimulated RAW 264.7 macrophages. GRC-ON89A-Hex decreased the inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and tumor necrosis factor (TNF)-α mRNA expression in LPS-stimulated RAW 264.7 macrophages. In addition, pre-treatment with GRC-ON89A-Hex significantly inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. To induce allergic contact dermatitis (ACD), 1-fluoro-2, 4-dinitrofluorobenzene (DNFB) was applied to the surface of the right ears of C57BL/6N mice. GRC-ON89A reduced the ear swelling and thickness in DNFB-induced ACD mice. This study demonstrates the potential usefulness of GRC-ON89A as an anti-inflammatory dietary supplement or drug.

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PMID: 

Oncol Lett. 2018 Dec ;16(6):6930-6939. Epub 2018 Sep 27. PMID: 30546425

Abstract Title: 

fraction inhibits the invasion and metastasis of lung cancer cells through the protein kinase B/glycogen synthase kinase 3β/β-catenin signaling pathway.

Abstract: 

is widely used as a traditional Chinese medicine health supplement, and is also used in the development of anticancer agents. In our previous studies, it was revealed thatfraction (CMF) possessed an antitumor effect against K562 cells, induced apoptosis and caused cell cycle arrest in the S phase. The published results also demonstrated that CMF-induced apoptosis was involved in mitochondrial dysfunction. The aim of the present study was to investigate the anti-invasion and anti-metastasis effects of CMF in NCI-H1299 and Lewis lung cancer (LLC) cell lines, which have high metastatic potential. MTT and clone formation assays were initially used to investigate the inhibitory effect of CMF on the viability of NCI-H1299 and LLC cells. The results of cell adhesion, wound healing, migration and Matrigel invasion assaysindicated that NCI-H1299 cells (treated with 1, 3, 10 or 30µg/ml CMF) and LLC cells (treated with 0.1, 0.3, 1 or 3 µg/ml CMF) demonstrated a concentration-dependent reduction in cell migration and invasion compared with the control.experiments demonstrated that the oral administration of CMF (65, 130 or 260 mg/kg) decreased the tumor growth and decreased the lung and liver metastasis in an LLC xenograft model, compared with untreated mice. Furthermore, western blot analysis was used to investigate the mechanism of the effect of CMF on the migration of NCI-H1299 cells and metastasis in the xenograft model. The results revealed that CMF may promote glycogen synthase kinase 3β (GSK-3β)-mediated degradation of β-catenin inhibited the phosphorylation of upstream protein kinase B (Akt), which resulted in the attenuation of the expression of matrix metalloproteinase (MMP)-2 and MMP-9. These results suggested that CMF may possess potential for the treatment of lung cancermetastasis via the Akt/GSK-3β/β-catenin pathway.

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PMID: 

Food Chem Toxicol. 2019 Feb ;124:400-410. Epub 2018 Dec 18. PMID: 30576710

Abstract Title: 

Cordycepin, isolated from medicinal fungus Cordyceps sinensis, enhances radiosensitivity of oral cancer associated with modulation of DNA damage repair.

Abstract: 

Concurrent chemotherapy and radiotherapy (RT) is important for controlling oral squamous cell carcinoma (OSCC), which is often accompanied by significant acute and late toxicities. We investigated whether cordycepin, a small molecule extracted from Cordyceps sinensis, could enhance the radiosensitivity of oral cancer cells. Using colony formation assay, we demonstrated that cordycepin induces radiosensitizing effects on two OSCC cells. DNA histogram analysis showed that cordycepin combined with RT prolonged the RT-induced G2/M phase arrest. It protracted the duration of DNA double strand breaks, which was detected by immunofluorescent staining of phosphorylated histone H2AX (γ-H2AX). The underlying molecular mechanism might involve the downregulation of protein expression related to DNA damage repair, including phosphorylated ataxia-telangiectasia mutated (p-ATM) and phosphorylated checkpoint kinase 2. Reciprocal upregulation of phosphorylated checkpoint kinase 1 (Chk1) expression was noted, and the radiosensitizing effect of cordycepin could be further augmented by Chk1 mRNA knockdown, indicating a compensatory DNA repair machinery involving phosphorylation of Chk1. In vivo, the combination of cordycepin and RT exhibited greater growth inhibition on xenografts and stronger apoptosis induction than RT alone, without exacerbating major toxicities. In conclusion, cordycepin increased the radiosensitivity of OSCC cells, which is associated with the modulation of RT-induced DNA damage repair machinery.

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PMID: 

Nutrients. 2018 Dec 21 ;11(1). Epub 2018 Dec 21. PMID: 30577618

Abstract Title: 

Grown on Germinated Soybean Suppresses KRAS-Driven Colorectal Cancer by Inhibiting the RAS/ERK Pathway.

Abstract: 

is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whetheron germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer which is notorious for its un-druggable features and the ineffectiveness of conventional therapies against it. GSC extract was prepared and its proximate composition and amino acids were analyzed. The suppressive effects were investigated with the KRAS-driven colorectal cancer cell-line, SW480. SW480 proliferation, clonogenic potential, apoptosis, and the RAS/extracellular signal-regulated kinase (ERK) pathway under the GSC treatment were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry, and Western blot, respectively. Anexperiment with the SW480 xenograft mouse model was performed. As a result, GSC suppressed cell proliferation by inducing the apoptosis of KRAS-driven colorectal cancer cells and inhibited clonogenic capabilities. The decrease of KRAS and ERK phosphorylation was detected by Western blot. Tumor growth was significantly suppressed when GSC was introduced to the tumor-xenograft mouse model. In conclusion, GSC suppressed KRAS-driven colorectal cancer growth both in vitro and in vivo, and can be used as an alternative or simultaneous approach in colorectal cancer therapy.

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