Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/96062
標題: Functional activity and safety of Cordyceps cicadae
蟬花功能性及安全性之研究
作者: Yen-Lien Chen
陳炎鍊
關鍵字: 大蟬花
安全性評估
調節血糖
胰島素抗性
葡萄糖耐性測定
Cordyceps cicadae
Safety evaluation
Blood glucose regulation
Insulin resistance
Glucose tolerance test
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摘要: 大蟬花(Cordyceps cicadae)為傳統中藥材,入藥已有一千多年歷史,研究顯示具有多樣生理活性,其成分及功效與冬蟲夏草相似。近年來,開始有液態發酵菌絲體進行工業化放大生產的研究和功能的探討。本研究以自台灣北部山區所採集、分離之大蟬花為菌種樣品,並以深層發酵培養菌絲體,依據衛福部公告之健康食品安全性和調節血糖功能評估方法,進行大蟬花菌絲體第三類安全性評估試驗和調節血糖功能評估試驗。 本研究利用液態發酵技術培養大蟬花菌絲體,進行三項基因毒性和單一劑量口服急性毒性試驗的評估。在沙門氏菌回復突變試驗中,無論是否經過S9 mix處理,對Salmonella typhimurium TA98、TA100、TA102、TA1535及TA1537菌株之回復突變菌落數,與負對照組相較,均未達陽性判定標準。在體外哺乳類細胞染色體結構異常試驗中,以哺乳類細胞CHO-K1在不含S9下作用3小時、18小時以及含有S9下作用3小時之三種方式處理下,均未造成細胞5 %以上染色體差異,且與負對照組之間無顯著差異。因此,判定試驗結果為陰性反應。另外,在囓齒類動物體內週邊血液微核試驗中,觀察測試劑量之多染性紅血球的比例(polychromatic erythrocytes, PCE %)及微核率(micronucleus frequency, MN ‰ PCE)均與負對照組無顯著差異,顯示大蟬花菌絲體不會抑制小鼠之造血功能。在口服急性毒性試驗中,SD大鼠經口餵食單一高劑量12g/kg b.w.後,活動狀況正常。在7天試驗期間,體重增長百分率(%)、臨床症狀及解剖肉眼檢查與對照組皆無差異。綜合上述試驗結果得知,大蟬花菌絲體發酵液凍乾粉不具有基因毒性和急毒性。 在大蟬花菌絲體對大鼠胚胎發育之影響及造成畸胎的可能性研究中,共設置4組試驗組,每組至少20隻成功懷孕的雌性大鼠Sprague-Dawley(SD)品系大鼠,並於懷孕第20天將各組懷孕雌鼠麻醉後進行解剖,肉眼觀察外觀及內臟器官並未發現任何病變。大蟬花菌絲體處理之各劑量組與陰性對照組比較,無論在胎鼠平均重,性別比例,卵巢黃體數,胎兒著床數,胎兒再吸收數,胚胎再吸收數,死胎數和著床後死亡率在統計上並無差異。在胎鼠外觀內臟和骨骼檢查方面,其實驗動物經餵食大蟬花菌絲體後並未造成畸胎現象。 在大鼠90 天重複劑量亞慢性毒性試驗中,共設置4 組試驗組,每組各使用10 隻雄性及雌性Sprague-Dawley(SD)品系大鼠,以經口管餵方式連續90 天投予大蟬花菌絲體,每日進行試驗動物之臨床觀察,且每週測量試驗動物之體重及攝食量。試驗結果顯示,所有試驗大鼠均無出現異常之臨床症狀;各劑量組大鼠均能正常增重,而眼睛檢查結果顯示各組大鼠均無異常。試驗結束時之尿液學檢查、血液學檢查、血清生化學檢查結果顯示各劑量組和對照組間並無明顯差異。病理解剖、肉眼病理學檢查以及組織病理學檢查結果顯示,各劑量組和對照組大鼠均無顯現任何與大蟬花菌絲體有關之病變。 以遺傳性9週齡雄性db/db糖尿病小鼠模式評估調節血糖功能,分正常對照組、負對照組、低劑量組(215.25mg/kg )、中劑量組(430.5mg/kg ),高劑量組(1076.25mg/kg )共五組,每組8隻雄性db/db小鼠進行連續9週餵食試驗。試驗結果指出,低、中、高劑量組肝臟重量明顯降低 (p < 0.05),減緩肝臟增重的現象。血糖指標結果顯示,低劑量(低劑量組,215.25 mg/kg BW)的組別,即可展現良好的血糖調節功效,可降低空腹血糖、果糖胺、胰島素抗性 (p < 0.05);在口服葡萄糖耐受性實驗第 0 ~ 180 分鐘的血糖濃度數值明顯低於負對照組 (p < 0.05);計算血糖值曲線下面積,低劑量組的數值明顯比負對照組低 (p < 0.05)。綜合動物試驗結果,大蟬花菌絲體在遺傳性糖尿病 db/db 小鼠試驗模式條件下具有調節胰島素、空腹血糖、果糖胺、降低胰島素抗性、減緩餐後血糖的快速上升和促使血糖恢復平穩之輔助調節血糖功效。本研究之低劑量組的劑量,相當於成人(60公斤)每日攝取 2 顆之大蟬花菌絲體膠囊,可以參考作為建議攝取量。
Cordyceps cicadae is an edible and traditional medicinal mushroom that possess multiple bio-activities. 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. In this study, the collected C. cicadae samples from the mountains of New Taipei City in Taiwan were applied as the species for the production of mycelia. After being sequenced, the specimens were deposited at Bioresource Collection and Research Center at Food Industry Research and Development Institute and were applied for the studies of safety evaluation, as well as functional tests. In this study, three genotoxicity safety tests (Ames, chromosomal aberration, and bone marrow cell micronucleus tests) and single dose oral acute toxicity of freeze-dried C. cicadae mycelium powder, which is produced by liquid fermentation technology, were conducted for the studies of the product toxicity. In vitro bacterial testing method of gene mutation, it was shown no significant differences between treatment and the negative control group when we tested with Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537 strains with or without metabolic activation system (S9 mixture). In vitro chromosomal aberration test, the incidence of structural chromosomal aberrations ability in cultured mammalian cells (CHO-K1)was used to identify the genotoxicity. The results showed less than 5 % chromosome mutated in the three metabolic systems (3 hrs w/ S9, 3 hrs w/o S9 and 18 hrs w/o S9) and no significant difference with control group. In vivo micronucleus testing of rodent peripheral blood, the polychromatic erythrocytes proportion (PCE %) and micro-nuclear frequency of ICR mice (MN ‰ PCE) were analyzed and were indicated with no difference between treatment and control group. The results indicated that C. cicadae mycelium does not inhibit the hematopoietic function of mice. In acute oral toxicity study, there was no significant effects on physical conditions after oral feeding a single high dose of 12 g / kg (b.w.) in SD rats. The results showed that there was no difference between the control group and treatment group on body weight gains (%), clinical symptoms and observations on the gross necropsy during continuous observation of seven days. These results conclude that C. cicadae mycelium does not provoke mutagenicity, genotoxicity and acute toxicity in these systems. The prenatal developmental toxicity of the C. cicadae mycelium was conducted according to the guideline of Safety Evaluation Methods for Health Food Products, category 3, provided by the Ministry of Health and Welfare, Executive Yuan, Taiwan. A total of 4 test groups were performed in the study. A minimum of 20 sucessfully conceiving female Sprague-Dawley rats were studied in each group. On the 20th day of pregnancy, the rats were anesthetized, caesarean sections were performed, and macroscopic examinations were conducted. No macroscopic lesion was observed. The average weight of the fetal rats, gender ratio, number of corpora lutea, number of implantations, number of reabsorbed fetuses, number of still births, and the fatality rate of the C. cicadae mycelium test groups and negative control group exhibited no statistical differences. According to the results of the fetal appearance, organ, and bone examination, no fetal deformations were caused by the C. cicadae mycelium. Sub-cute toxicity study was conducted to evaluate the possible toxicity arising from repeated exposure of submerge-cultured and freeze-dried mycelial culture of C. cicadae for 90 days. A total of 80 8-week old Sprague-Dawley (SD) rats were divided into four groups (10 males and 10 females for each group). No animal death and no treatment-related clinical signs were observed during the study period. No statistical difference was observed in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis. The gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent for functional food. In the hypoglycenic effects study, the db/db diabetic mouse model was used to study the effects of C. cicadae mycelium on hyperglycemia of type 2 diabetes. Nine weeks old male db/db diabetic mouse group, the normal control group , negative control group, low dose group (215.25mg / kg), medium dose group (430.5mg / kg) and high dose group (1076.25mg / kg) were fed for 9 consecutive weeks. Results indicate that significantly lower liver weights were found in low , medium and high dose groups after 9 weeks of continuous feeding. Glycemic index results showed that the effects of fasting blood sugar, fructosamine and insulin resistance were significantly (p <0.05) ameliorated the low dose group (215.25 mg / kg BW). Blood glucose concentration values in the oral glucose tolerance test 0 to 180 minutes were significantly lower than the negative control group (p <0.05 ) ; blood glucose level calculated area under the curve , the value of low dose group was significantly lower than the negative control group (p <0.05 ) . Comprehensive results of animal testing , C. cicadae mycelium has to adjust insulin, fasting glucose, fructosamine, lipid levels, reduce insulin resistance, slow down the rapid rise in blood sugar after a meal and promote blood sugar steady recovery of the efficacy regulating blood sugar in genetically diabetic db/db mice test model condition. Low dose group of the present study, the adult equivalent of a daily intake of two C. cicadae mycelium capsule, you can refer to as the recommended dietary allowance. C. cicadae possesses multiple pharmacological activities and offers several featured advantages such as low toxicity, low price and easy availability of raw materials from artificial cultivation, paving a broad way for functional products.
URI: http://hdl.handle.net/11455/96062
文章公開時間: 10000-01-01
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