摘要
目的：牛樟芝是台湾的一种珍贵药用真菌,主要用于癌症的辅助治疗.本研究目的在于阐明牛樟芝在S180荷瘤小鼠肿瘤组织中的代谢产物以及它们的含量.方法：分别于S180荷瘤小鼠灌胃牛樟芝提取物1小时和4小时后取出肿瘤,采用UHPLC-orbitrap/MS方法鉴定肿瘤匀浆样品中的代谢产物,并建立LC-MS/MS方法对其中含量最高的两个化合物（25R/S）-antcin H定量分析.结果：从肿瘤组织共鉴定28个三萜原型和5个代谢产物,其中,（25R）-antcin H和（25S）-antcinH的含量最高,在1小时给药组的浓度分别为2.03和0.66μg/g肿瘤组织,在4小时给药组的浓度分别为2.04和0.59μg/g.由于（25R）-antcin H在牛樟芝提取物中的含量低于（25S）-antcin H,因此推测（25R）-antcin H的肿瘤亲和力高于（25S）-antcin H（P〈0.01）.结论：口服牛樟芝之后,三萜类成分能够进入肿瘤组织.其中,（25R）-antcin H在肿瘤组织中的浓度比（25S）-antcin高.这些化合物对于牛樟芝的抗肿瘤活性可能发挥重要作用.
Objective： Antrodia camphorata （AC）, a precious medicinal mushroom in Taiwan, is popularly used for adjuvant cancer therapy. This paper aims to clarify the metabolites which are present in tumor tissues after oral administration of AC in Sarcoma-180 tumor-bearing mice, as well as their contents in tumors. Methods： Tumors of Sarcoma-180 tumor-bearing mice were obtained at 1 h and 4 h after oral administration of AC extract, and the metabolites in the tumor homogenate samples were characterized using UHPLC-orbitrap/MS analysis. Then, a fully validated LC-MS/MS method was developed for quantitative analysis of the most abundant compounds in tumor tissues, namely （25R/S）-antcin H. Results： A total of 33 compounds were characterized in tumor homogenate samples including 28 prototypes of triterpenoids and 5 metabolites. Among them, （25R）-antcin H and （25S）-antcin H had the highest contents of 2.03 and 0.66 μg/g tumor tissues for the 1 h group, and 2.04 and 0.59 μg/g tumor tissues for the 4 h group, respectively. It was obvious that （25R）-antcin H had higher tumor affinity than （25S）-antcin H, since the content of （25R）-antcin H was lower than that of （25S）-antcin H in AC extract （P 〈 0.01）. Conclusion： Triterpenoids can enter tumor tissues after oral administration of AC. Particularly, （25R）-antcin H showed higher exposure to tumor than （25S）-antcin H. These compounds could contribute to the anticancer activities of AC.
基金
This work was supported by National Natural Science Foundation of China （No. 81303294）, the National Key Research and Development Program of China （No. 2017YFC1700405）, and Young Elite Scientists Sponsorship Program by CAST （2016QNRC001）.
