Grape King Biotechnology Inc.

Zhongli, Taiwan

Grape King Biotechnology Inc.

Zhongli, Taiwan
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PubMed | Chang Gung Memorial Hospital, Chang Gung University and Grape King Biotechnology Inc.
Type: | Journal: Journal of translational medicine | Year: 2016

Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinsons disease, which results in motor disturbances, in addition to elucidating the mechanisms involved.Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination.Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB- and NF-B, as well as Fas and Bax.These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinsons disease, and this protective effect seems to exist both in vivo and in vitro.


Li I.-C.,Grape King Biotechnology Inc | Chen Y.-L.,National Chung Hsing University | Chen W.-P.,Grape King Biotechnology Inc | Lee L.-Y.,Grape King Biotechnology Inc | And 3 more authors.
Toxicology Reports | Year: 2014

Hericium erinaceus (H. erinaceus) has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF) from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo. With increasing recognition of erinacine A in H. erinaceus (EAHE) mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests) according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions. © 2014 The Authors.


Li I.-C.,Grape King Biotechnology Inc. | Chen Y.-L.,Grape King Biotechnology Inc. | Lee L.-Y.,Grape King Biotechnology Inc. | Chen W.-P.,Grape King Biotechnology Inc. | And 3 more authors.
Food and Chemical Toxicology | Year: 2014

Natural products have attained great importance as they are believed to be the new alternative medicines for conventional therapy. As numerous studies have proved the tremendous medicinal values of Hericium erinaceus, it is necessary to take into account its safety as well as its risk for the recipient. However, mushroom mycelium has an identity distinct from mushrooms, as two specific classes of compounds, hericenones and erinacines, can only be extracted from both the fruit body and the cultured mycelium, respectively. Therefore, this is the first report on the evaluation of the toxicity of H erinaceus mycelium, enriched with 5. mg/g erinacine A, by a 28-day repeated oral administration study in Sprague-Dawley rats. Three doses of 1 (Low), 2 (Mid) and 3 (High) g/kg body weight/day were selected for the study while distilled water served as control. All animals survived to the end of the study. No abnormal changes were observed in clinical signs. No adverse or test article-related differences were found in urinalysis, haematology and serum biochemistry parameters, between the treatment and control groups. No gross pathological findings and histopathological differences were seen. Therefore, the no-observed-adverse-effect level of erinacine A-enriched H. erinaceus is greater than 3. g/kg. body weight/day. © 2014 Elsevier Ltd.


Chen T.-I.,Grape King Biotechnology Inc. | Chen C.-C.,Grape King Biotechnology Inc. | Lin T.-W.,Grape King Biotechnology Inc. | Tsai Y.-T.,Super Laboratory Inc. | Nam M.-K.,Super Laboratory Inc.
Food and Chemical Toxicology | Year: 2011

Antrodia cinnamomea (Ac) is a medicinal mushroom widely used for the treatment of abdominal pain, hypertension and hepatocellular carcinoma, but subchronic toxicity of this material has not yet been investigated. This present study was conducted to assess the 90-day oral toxicity of A. cinnamomea from submerged culture in male and female Sprague-Dawley (SD) rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. Test articles were administered by oral gavage to rats at 3000, 2200 and 1500. mg/kg BW/day for 90 consecutive days and reverse osmosis water was used as control. All animals survived to the end of the study. During the experiment period, no abnormal changes were observed in clinical signs, body weight and ophthalmological examinations. No significant differences were found in urinalysis, hematology and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. According to the above results, the no-observed-adverse-effect level (NOAEL) of Antrodia cinnamomea is identified to be greater than 3000. mg/kg BW/day in Sprague-Dawley rats. © 2010 Elsevier Ltd.


Chen Y.-L.,National Chung Hsing University | Yeh S.-H.,Grape King Biotechnology Inc. | Lin T.-W.,Grape King Biotechnology Inc. | Chen C.-C.,Grape King Biotechnology Inc. | And 3 more authors.
International Journal of Medicinal Mushrooms | Year: 2015

Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague-Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be >2000 mg/kg for male and female Sprague-Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food. © 2015 Begell House, Inc.


PubMed | Grape King Biotechnology Inc., Shih Chien University and National Chung Hsing University
Type: Journal Article | Journal: International journal of medicinal mushrooms | Year: 2015

Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague-Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be > 2000 mg/kg for male and female Sprague-Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food.


Chiu C.-H.,Hungkuang University | Peng C.-C.,Taipei Medical University | Ker Y.-B.,Hungkuang University | Chen C.-C.,Grape King Biotechnology Inc. | And 4 more authors.
Molecules | Year: 2014

Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its bioproducts have been used to meet the market demand for natural fruiting bodies. AC exhibits anti-inflammatory, antitumor, antioxidant, and immunomodulatory effects. Previously, we isolated polysaccharide AC-2 from AC mycelia by means of alkali extraction with subsequent acid precipitation and found it had a pronounced anti-inflammatory effect. In this study, a novel polysaccharide named "antrodan" was obtained by further purification of AC-2 using Sepharose CL-6B column chromatography. Antrodan exhibited a molecular weight of 442 kD and contained a particularly high content of uronic acid (152.6 ± 0.8 mg/g). The protein content was 71.0%, apparently, higher than the carbohydrate content (14.1%), and thus antrodan was characterized as a glycoprotein. Its total glucan content was 15.65%, in which β-glucan (14.20%) was prominently higher than a-glucan (1.45%). Its FTIR confirmed the presence of β-linkages between sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR spectrum showed that antrodan was a complex union of a- and β-glucans, which had (1-4)-linked a-Glcp and (1-3)-linked β-Glcp linkages to the carbohydrate chains via asparagine linked to protein site. Biologically, antrodan was confirmed to be totally non-detrimental to RAW 264.7 cell line even at dose as high as 400 μg/mL. It showed potent suppressing effect on the lipopolysaccharide-induced inflammatory responses in RAW 264.7 cell line. Moreover, antrodan significantly reduced the nitrogen oxide production at doses as low as 18.75 μg/mL.© 2014 by the authors licensee MDPI Basel Switzerland.


Lu M.-Y.,Shih Chien University | Chen C.-C.,Shih Chien University | Chen C.-C.,Grape King Biotechnology Inc. | Lee L.-Y.,Grape King Biotechnology Inc. | And 2 more authors.
Journal of Natural Products | Year: 2015

Natural products play an important role in promoting health with relation to the prevention of chronic inflammation. N6-(2-Hydroxyethyl)adenosine (HEA), a physiologically active compound in the medicinal mushroom Cordyceps cicadae, has been identified as a Ca2+ antagonist and shown to control circulation and possess sedative activity in pharmacological tests. The fruiting body of C. cicadae has been widely applied in Chinese medicine. However, neither the anti-inflammatory activities of HEA nor the fruiting bodies of C. cicadae have been carefully examined. In this study, we first cultured the fruiting bodies of C. cicadae and then investigated the anti-inflammatory activities of water and methanol extracts of wild and artificially cultured C. cicadae fruiting bodies. Next, we determined the amount of three bioactive compounds, adenosine, cordycepin, and HEA, in the extracts and evaluated their synergistic anti-inflammatory effects. Moreover, the possible mechanism involved in anti-inflammatory action of HEA isolated from C. cicadae was investigated. The results indicate that cordycepin is more potent than adenosine and HEA in suppressing the lipopolysaccharide (LPS)-stimulated release of pro-inflammatory cytokines by RAW 264.7 macrophages; however, no synergistic effect was observed with these three compounds. HEA attenuated the LPS-induced pro-inflammatory responses by suppressing the toll-like receptor (TLR)4-mediated nuclear factor-κB (NF-κB) signaling pathway. This result will support the use of HEA as an anti-inflammatory agent and C. cicadae fruiting bodies as an anti-inflammatory mushroom. © 2015 The American Chemical Society and American Society of Pharmacognosy.

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