奈米化中草藥與健康食品安全性及功效研究

Safety and Efficiency Study of a Nanoscale Chinese Herb Medicine and Health Food

黃筱嵐(Hsiao-Lan Huang)

指導教授 ： 張恒雄

中原大學/工學院/生物醫學工程研究所/博士(2011年)

https://doi.org/10.6840/cycu201101006

摘要

由於繁重的工作壓力與緊湊的生活步調，健康食品的市場不斷快速成長。而長久以來，中華文化裡藥食同源的概念，也使得保健養生的觀念深植民心，人們希望透過健康食品的幫助，達到改善身體機能的功效。但是，由於中草藥與健康食品在人體的吸收效率普遍不佳，往往需要服用一定的劑量才足夠，因此奈米化中草藥與健康食品被發展出來，希望運用奈米化的特性促進中草藥與健康食品在人體的吸收效率與生物活性。本研究分為兩部分，分別探討奈米碳酸鈣與奈米檸檬酸鈣以及奈米化保肝中藥湯劑的生物效應。
第一部分: 服用鈣質補充品可以降低罹患骨質疏鬆症的風險，但是鈣劑相關健康食品在腸胃道的吸收效率低，因此希望近年來新興的奈米科技能改善健康食品吸收效率不佳的問題。本研究探討若降低碳酸鈣與檸檬酸鈣粒徑大小是否能增加其生物利用率，在奈米碳酸鈣與奈米檸檬酸鈣的粒徑大小部分以動態雷射光散射儀(Dynamic laser-light scattering; DLS) 量測，而外觀特性則以場發射掃描式電子顯微鏡(Field-emission scanning electron microscopy; FE-SEM) 及穿透式電子顯微鏡(Transmission electron microscopy; TEM) 觀察，最後將這些型態分析進行比較。在口服安全性部分則進行急毒性與亞慢毒性測試，結果發現奈米碳酸鈣與奈米檸檬酸鈣的無觀察危害反應劑量分別為1.3克/每公斤體重與 2.3克/每公斤體重，而奈米碳酸鈣與奈米檸檬酸鈣可提升血清鈣濃度，並且可以減少卵巢切除雌鼠骨質流失的情形。
第二部分: 傳統常用的保肝中藥方劑: 三黃瀉心湯(San-Huang-Xie-Xin-Tang decoction) 由大黃、黃芩與黃連組成，而其在煎煮的過程中會造成有效成分的流失，因此開發了奈米化三黃瀉心湯以增進其生物利用率。本研究以氯仿誘導小鼠肝臟纖維化為疾病動物模式，而以肝臟星狀細胞為體外細胞培養研究模式，由疾病動物模式結果發現，奈米化三黃瀉心湯可以使肝臟重量/體重比、血清麩胺酸苯醋酸轉氨基酵素(Aspartate aminotransferase; AST) 與血清胺基丙酮酸轉化酵素(Alanine aminotransferase; ALT) 回復正常值，而受活化的肝臟星狀細胞中，基質金屬蛋白酵素組織抑制因子(Tissue inhibitor of metalloproteinase-1; TIMP-1) mRNA表現量因奈米化三黃瀉心湯而受到抑制，而基質金屬蛋白酵素-2(Matrix melloproteinase-2; MMP-2) mRNA表現量則增加，由此可知，在室溫下以水萃取的奈米化三黃瀉心湯仍具有保肝功效。
由結果得知，奈米碳酸鈣、奈米檸檬酸鈣以及奈米化三黃瀉心湯的生物利用率優於微米碳酸鈣、微米檸檬酸鈣與傳統三黃瀉心湯，而且奈米化三黃瀉心湯的萃取更為方便，奈米化三黃瀉心湯的製備省去熬煮的時間，不但便利而且可以節約能源。因此奈米中草藥與健康食品與傳統中草藥與健康食品比較起來有許多優勢，其生物利用率增加及生物體的吸收力提高，並可降低使用劑量即具有功效。

關鍵字

鈣 ； 奈米科技 ； 骨質疏鬆 ； 草藥 ； 肝纖維化

並列摘要

Health food is one of the several areas in the food industry that is experiencing fast growth in recent years. Herb medicine is treated as a health food to provide specific favorable effects on health for a long time. However, the absorption efficiency of traditional herb medicines and health foods in the gastrointestinal tract is lower. A number of new nanotechnology-based herb medicines and health foods have been developed that have efficient biopharmaceutical properties. In this study, the bioeffects of nanoscale calcium carbonate, calcium citrate, and a hepatoprotective herbal decoction were evaluated.
Study1: Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to reform this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM, and TEM were comparable. Acute and subchronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g/kg body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice.
Study 2: San-Huang-Xie-Xin-Tang decoction, a traditional Chinese medicine containing Rhei rhizoma, Coptidis rhizome, and Scutellariae radix, is widely used in hepatoprotective therapy. However, the preparation of the decoction requires boiling water that loses numerous efficient components. To improve the bioavailability of the decoction, nanoscale San-Huang-Xie-Xin-Tang was developed. CHCl3-induced liver injury mice and hepatic stellate cells were applied to demonstrate the hepatoprotective character of the nanoscale San-Huang-Xie-Xin-Tang decoction. The liver/body weight ratio and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were recovered by nanoscale San-Huang-Xie-Xin-Tang. The tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression was inhibited, and matrix melloproteinase-2 (MMP-2) gene expression was accelerated in activated HSC. This new method could retain the hepatoprotective ability of nanoscale San-Huang-Xie-Xin-Tang decoction prepared in room temperature water.
In conclusion, these data suggest that nano calcium carbonate, nano calcium citrate, and nanoscale San-Huang-Xie-Xin-Tang are more bioavailable than micro calcium carbonate, micro calcium citrate, and traditional San-Huang-Xie-Xin-Tang, respectively. Furthermore, nanoscale San-Huang-Xie-Xin-Tang can be extracted easily. The simple preparation of herbal decoction is more convenient and energy efficient. Nanoparticles of herb medicines and health foods possess many benefits such as enhanced bioavailability, increased absorbency by the organism, and reduced medicinal doses compared to traditional herb medicine and health food preparations.

並列關鍵字

calcium ； nanotechnology ； osteoporosis ； herb medicine ； liver fibrosis

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