天麻水萃物之安全性評估

Abstract

天麻 (Gastrodia elata Blume) 為一種多年生蘭科草本植物 (Orchidaceae Family)，產地多分布於亞洲東部，尤其是中國、韓國、日本和印度山區，為一種常用於中醫以及民間食療的中草藥。天麻水萃物 (water extract of Gastrodia elata Blume, WGE) 在近年來受到廣泛地研究，目前已有文獻指出WGE具有抗憂鬱、改善空間學習及記憶，以及改善代謝相關疾病(例如:糖尿病)等多種功效，因此具有開發成為保健產品的高度潛力。過去研究中提及天麻粗萃取物及其活性成分於囓齒動物注射下的毒性是非常低的，但也有少部分於人體個案中提及天麻在不當使用下可能會造成皮疹、暈眩，甚至是嚴重的過敏性休克等，而目前尚缺乏完整的安全性資料來確立WGE 於保健食品開發以及大量食用上的風險。依據衛生福利部公告之健康食品安全性評估方法，WGE屬於第二類，須進行的毒性測試項目包含基因毒性試驗及 28天亞急毒性試驗。因此本研究利用微生物、細胞以及動物實驗的基因毒性檢測方法，並且利用WGE在抗憂鬱動物實驗之有效劑量估計人體相對應之建議攝取量，乘以30、60及100倍之安全邊際係數 (Margin of safety, MOS) 作為試驗劑量，進行WGE的28 天亞急毒性試驗作為安全性評估，以建立WGE在相關研究上所使用的安全劑量以及消費者安全食用量之依據。基因毒性試驗結果顯示，WGE在安姆氏細菌回復突變試驗中，在Salmonella typhimurium的TA98、TA100、TA102、TA1535及TA1537菌株測試下均未產生致突性，且並不會增加CHO-k1細胞染色體的變異率，小鼠周邊血液中之血球微核發生率也未發生顯著提高的情形。28天亞急毒性試驗的結果顯示，WGE在臨床觀察無不良反應產生，並且血清生化及血液學分析也落於正常範圍中，組織病理學的切片分析也未呈現不良反應之結果，因此於本研究中判讀WGE之無毒性顯示劑量(no-observed-adverse-effect level, NOAEL) 值為高於8065 mg/kg bw，乃人體建議攝取量87.65 mg/kg bw之乘以安全係數100之劑量，由此可提供給WGE相關功效研究及保健食品開發上之可應用之劑量參考。

Abstract Gastrodia elata Blume (Tianma) is a kind of Orchidaceae Family plants, which is mainly distributed in the mountainous areas of eastern Asia, especially in China, South Korea, Japan and India. It’s also a kind of herbal medicine commonly used in Chinese medicine, folk remedy and dietary therapy. Water extract of Gastrodia elata Blume (WGE) has also been widely researched. Currently, many studies have shown that WGE has a variety of effects such as anti-depression, improvement of space learning and memory, and metabolic-related diseases such as diabetes. Therefore, WGE has the great potential for development of healthy food products. A previous study was mentioned that the toxicity of Tianma and its active compositions are very low under injection in animal experiment, but a clinical case showed that Tianma possibly caused rash, dizziness, and even severe anaphylactic shock. It is still lack of whole safety information of WGE in healthy food development or massive consumption. WGE belongs to the class 2 healthy food according to the regulations of Healthy Food Safety Assessment announced by the Ministry of Health and Welfare in Taiwan. The healthy food in class 2 have to perform toxicity tests includes genotoxicity test and 28-day subacute toxicity test. Therefore, in this study I used the microorganism and animal models to evaluate genotoxicity of WGE. Moreover, I performed the 28-day repeated-dose toxicity study in mice by referencing the effective dose in antidepressant animal experiments corresponding to the recommended daily intake of human which is multiplied by the Margin of Safety (MOS) in 30, 60 and 100 to establish safe dosage of WGE. The results of genotoxicity test showed that WGE not only had no potential of mutagenicity under testing Salmonella typhimurium strains (TA98, TA100, TA102, TA1535 and TA1537) , but also did not significantly raise the aberrations rate in CHO-k1 cells and incidence of micronucleus in red blood cells in peripheral blood of mice. Moreover, in the 28-day repeated-dose toxicity study revealed that no adverse reaction in clinical observation, blood biochemistry, hematology and histopathological examination. Therefore, the no-observed-adverse-effect level (NOAEL) in WGE is the dosage over 8065 mg/kg body weight in this study. It could provide the safety dosage of WGE to functional researches and healthy food development.