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Yong T.,Guangdong Institute of Microbiology | Yong T.,Guangdong Yuewei Edible Fungi Technology Co. | Zhang M.,Guangdong Yuewei Edible Fungi Technology Co. | Chen D.,Guangdong Institute of Microbiology | And 7 more authors.
Journal of Ethnopharmacology | Year: 2016

Ethnopharmacological relevance Cordyceps militaris was recorded in the classic traditional Chinese medicine book with the main functions of “protecting liver and enhancing kidney functions”, influencing serum uric acid levels. Aim of study The aim is to investigate the hypouricemic effects and possible mechanism of C. militaris in hyperuricemic mice. Materials and methods A water extract (WECM) was prepared by decocting C. militaris directly at 80 °C in water bath, followed by lyophilization. WECM at 50, 100 and 200 mg/kg was orally administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine combinedly and allopurinol (5 mg/kg) was served as a positive control. Results WECM exhibited excellent hypouricemic activity, which could decrease the serum uric acid levels of the hyperuricemic mice (306 μmol/L) to 189, 184 and 162 μmol/L at different doses respectively (P<0.01), approaching the levels of normal mice (184 μmol/L). The urate transporter 1 (URAT1) protein levels of kidney at different doses of WECM were 28.15, 17.43, 9.03 pg/mL respectively, much lower than that in the hyperuricemia group (93.45 pg/mL, P<0.01); and suggested WECM may interact with URAT1. Docking simulations using modeled structure of URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key functional residues of URAT1. Four active compounds in C. militaris were identified and their interaction energies with target were estimated between −200 and −400 kcal/mol. Conclusions These findings suggested that C. militaris produced significant hypouricemic actions and the hypouricemic effects of WECM may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The results of blood urine nitrogen and serum creatinine levels and liver, kidney and spleen coefficients showed that WECM have no negative impacts on liver, renal and spleen functions. The screened four active compounds using molecular docking method deserve further investigation in other work. © 2016 Elsevier Ireland Ltd


Pan H.-H.,Guangdong Institute of Microbiology | Yu X.-T.,Guangdong Institute of Microbiology | Li T.,Chinese Academy of Sciences | Wu H.-L.,Chinese Academy of Sciences | And 8 more authors.
International Journal of Medicinal Mushrooms | Year: 2013

Chaga medicinal mushroom, Inonotus obliquus, a popular prescription in traditional medicine in Europe and Asia, was used to reduce inflammation in the nasopharynx and to facilitate breathing. The aqueous extract from I. obliquus (AEIO) exhibited marked decrease in herpes simplex virus (HSV) infection (the 50% inhibitory concentration was 3.82 μg/mL in the plaque reduction assay and 12.29 μg/mL in the HSV-1/blue assay) as well as safety in Vero cells (the 50% cellular cytotoxicity was >1 mg/mL, and selection index was >80). Using a time course assay, effective stage analysis, and fusion inhibition assay, the mechanism of anti-HSV activity was found against the early stage of viral infection through inhibition of viral-induced membrane fusion. Therefore, AEIO could effectively prevent HSV-1 entry by acting on viral glycoproteins, leading to the prevention of membrane fusion, which is different from nucleoside analog antiherpetics. © 2013 Begell House, Inc.


Diling C.,Guangdong Institute of Microbiology | Chaoqun Z.,Guangdong Institute of Microbiology | Chaoqun Z.,Guangzhou University | Jian Y.,Guangdong Institute of Microbiology | And 7 more authors.
Frontiers in Immunology | Year: 2017

A single-band protein (HEP3) was isolated from Hericium erinaceus using a chemical separation combined with pharmacodynamic evaluation methods. This protein exhibited immunomodulatory activity in lipopolysaccharide-activated RAW 264.7 macrophages by decreasing the overproduction of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and downregulating the expression of inducible nitric oxide synthase and nuclear factor-κB p65. Further researches revealed that HEP3 could improve the immune system via regulating the composition and metabolism of gut microbiota to activate the proliferation and differentiation of T cells, stimulate the intestinal antigen-presenting cells in high-dose cyclophosphamide-induced immunotoxicity in mice, and play a prebiotic role in the case of excessive antibiotics in inflammatory bowel disease model mice. Aided experiments also showed that HEP3 could be used as an antitumor immune inhibitor in tumor-burdened mice. The results of the present study suggested that fungal protein from H. erinaceus could be used as a drug or functional food ingredient for immunotherapy because of its immunomodulatory activities. © 2017 Diling, Chaoqun, Jian, Jian, Jiyan, Yizhen and Guoxiao.


PubMed | Guangdong Yuewei Edible Fungi Technology Co., Guangdong Institute of Microbiology and China Institute of Technology
Type: | Journal: Journal of ethnopharmacology | Year: 2016

Cordyceps militaris was recorded in the classic traditional Chinese medicine book with the main functions of protecting liver and enhancing kidney functions, influencing serum uric acid levels.The aim is to investigate the hypouricemic effects and possible mechanism of C. militaris in hyperuricemic mice.A water extract (WECM) was prepared by decocting C. militaris directly at 80 C in water bath, followed by lyophilization. WECM at 50, 100 and 200mg/kg was orally administered to hyperuricemic mice induced by potassium oxonate and hypoxanthine combinedly and allopurinol (5mg/kg) was served as a positive control.WECM exhibited excellent hypouricemic activity, which could decrease the serum uric acid levels of the hyperuricemic mice (306mol/L) to 189, 184 and 162mol/L at different doses respectively (P<0.01), approaching the levels of normal mice (184mol/L). The urate transporter 1 (URAT1) protein levels of kidney at different doses of WECM were 28.15, 17.43, 9.03pg/mL respectively, much lower than that in the hyperuricemia group (93.45pg/mL, P<0.01); and suggested WECM may interact with URAT1. Docking simulations using modeled structure of URAT1 suggested that LYS145, ARG325, ARG477 and ASP168 of URAT1 are key functional residues of URAT1. Four active compounds in C. militaris were identified and their interaction energies with target were estimated between -200 and -400kcal/mol.These findings suggested that C. militaris produced significant hypouricemic actions and the hypouricemic effects of WECM may be attributed to the inhibitive effect of WECM on URAT1 protein levels. The results of blood urine nitrogen and serum creatinine levels and liver, kidney and spleen coefficients showed that WECM have no negative impacts on liver, renal and spleen functions. The screened four active compounds using molecular docking method deserve further investigation in other work.


Liu C.,Peking Union Medical College | Zhao C.,Peking Union Medical College | Pan H.-H.,Guangdong Institute of Microbiology | Kang J.,Peking Union Medical College | And 5 more authors.
Journal of Natural Products | Year: 2014

Seven new triterpenes, inonotusol A-G (1-7), one new diterpene, inonotusic acid (8), and 22 known compounds were isolated from Inonotus obliquus. Their structures were elucidated on the basis of spectroscopic analysis, including homonuclear and heteronuclear correlation NMR (1H-1H COSY, ROESY, HSQC, and HMBC) experiments. In in vitro assays, compounds 6 and 8-16 showed hepatoprotective effects against d-galactosamine-induced WB-F344 cell damage, with inhibitory effects from 34.4% to 81.2%. Compounds 7, 17, and 18 exhibited selective cytotoxicities against KB, Bel-7402, or A-549 cell lines. Compounds 16 and 17 showed inhibitory effects against protein tyrosine kinases, with IC50 values of 24.6 and 7.7 μM, respectively. © 2013 The American Chemical Society and American Society of Pharmacognosy.


Xie Y.-Z.,Guangdong Institute of Microbiology | Xie Y.-Z.,Guangdong Yuewei Edible Fungi Technology Co. | Yang F.,Guangdong Laboratory Animals Monitoring Institute | Tan W.,Guangdong Laboratory Animals Monitoring Institute | And 6 more authors.
Oncoscience | Year: 2016

To examine the role of oral Ganoderma spore oil in cardiovascular disease, we used transverse aortic constriction (TAC) in mice to model pressure overload-induced cardiomyopathy. Our preliminary results demonstrated a potential cardioprotective role for spore oil extracted from Ganoderma. We found that Ganoderma treatment normalized ejection fraction and corrected the fractional shortening generated by TAC. We also found evidence of reduced left ventricular hypertrophy as assessed by left ventricular end diastolic diameter. Analysis of total RNA expression using cardiac tissue samples from these mice corroborated our findings. We found reduced expression of genes associated with heart failure, including a novel circular RNA circ-Foxo3. Thus our data provides evidence for Ganoderma lucidum as a potential cardioprotective agent, warranting further preclinical exploration.


Huang J.-G.,Guangdong Institute of Microbiology | Huang J.-G.,Guangdong Yuewei Edible Fungi Technology Co. | Lv J.,Guangdong Yuewei Edible Fungi Technology Co. | Yu X.-T.,Guangdong Institute of Microbiology | And 7 more authors.
Modern Food Science and Technology | Year: 2015

The chemical composition, structure, and antiviral activity of ethyl acetate extracts of Inonotus obliquus was identified and analyzed. Inonotus obliquus is an edible and medical fungus with diverse and complex structures and a wide range of biological activities; in addition, this fungus has a low toxicity to humans and is rich in secondary metabolites. Inonotus obliquus fruit bodies were dried, ground, and sequentially extracted at room temperature using ethyl acetate, methanol, and water. Ten compounds were isolated from the ethyl acetate extract of Inonotus obliquus using various chromatographic techniques. Various modern spectroscopic methods of analysis and the data available in literature were used to identify the following compounds: betulin (1), inotodiol (2), 3-hydroxy-lanosta-8, 24-dien-21-al (3), 3β-hydroxytirucallic acid (4), ergosterol-5, 8-peroxide (5), 3β-hydroxy-5α, 8α-epidioxyergosta-6, 9, 22-triene (6), di(n-butyl) phthalate (7), 5-dehydroergosterol (8), pentacosanoic acid (9), and lignoceric acid (10). Among these, compounds 6 and 7 were isolated from Inonotus obliquus for the first time. Furthermore, the cytotoxicity and anti-HSV-1 activity of the isolated compounds 1~8 were also investigated. Compound 3 showed the strongest anti-HSV-1 activity, with a half maximal inhibitory concentration (IC50) of 98 μM; on the other hand, compound 7 exhibited the strongest cytotoxicity, with a 50% cytotoxic concentration (CC50) of 24 μM. This study provides a scientific basis for the future development of anti-HSV drugs from Inonotus obliquus. ©, 2015, South China University of Technology. All right reserved.


Li X.,Guangdong Institute of Microbiology | Li X.,Sunnybrook Research Institute | Li X.,University of Toronto | Wu Q.,Guangdong Institute of Microbiology | And 15 more authors.
Oncotarget | Year: 2016

Sterols are the important active ingredients of fungal secondary metabolites to induce death of tumor cells. In our previous study, we found that ergosterol peroxide (5a, 8a-epidioxiergosta-6, 22-dien-3β-ol), purified from Ganoderma lucidum, induced human cancer cell death. Since the amount of purified ergosterol peroxide is not sufficient to perform in vivo experiments or apply clinically, we developed an approach to synthesize ergosterol peroxide chemically. After confirming the production of ergosterol peroxide, we examined the biological functions of the synthetic ergosterol peroxide. The results showed that ergosterol peroxide induced cell death and inhibited cell migration, cell cycle progression, and colony growth of human hepatocellular carcinoma cells. We further examined the mechanism associated with this effect and found that treatment with ergosterol peroxide increased the expression of Foxo3 mRNA and protein in HepG2 cells. The upstream signal proteins pAKT and c-Myc, which can inhibit Foxo3 functions, were clearly decreased in HepG2 cells treated with ergosterol peroxide. The levels of Puma and Bax, pro-apoptotic proteins, were effectively enhanced. Our results suggest that ergosterol peroxide stimulated Foxo3 activity by inhibiting pAKT and c-Myc and activating pro-apoptotic protein Puma and Bax to induce cancer cell death.


Wu Q.-P.,Guangdong Institute of Microbiology | Xie Y.-Z.,Guangdong Institute of Microbiology | Xie Y.-Z.,Guangdong Yuewei Edible Fungi Technology Co. | Deng Z.,Sunnybrook Research Institute | And 20 more authors.
PLoS ONE | Year: 2012

Due to an altered expression of oncogenic factors and tumor suppressors, aggressive cancer cells have an intrinsic or acquired resistance to chemotherapeutic agents. This typically contributes to cancer recurrence after chemotherapy. microRNAs are short non-coding RNAs that are involved in both cell self-renewal and cancer development. Here we report that tumor cells transfected with miR-378 acquired properties of aggressive cancer cells. Overexpression of miR-378 enhanced both cell survival and colony formation, and contributed to multiple drug resistance. Higher concentrations of chemotherapeutic drugs were needed to induce death of miR-378-transfected cells than to induce death of control cells. We found that the biologically active component isolated from Ganoderma lucidum could overcome the drug-resistance conferred by miR-378. We purified and identified the biologically active component of Ganoderma lucidum as ergosterol peroxide. We demonstrated that ergosterol peroxide produced greater activity in inducing death of miR-378 cells than the GFP cells. Lower concentrations of ergosterol peroxide were needed to induce death of the miR-378-transfected cells than in the control cells. With further clinical development, ergosterol peroxide represents a promising new reagent that can overcome the drug-resistance of tumor cells. © 2012 Wu et al.

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