尖孢镰刀菌对滇产土牛膝的发酵改性研究

土牛膝是白族民间药，在云南分布广泛，但其开发非常有限。土牛膝含有大量植物甾酮，利用好土牛膝中的植物甾醇对土牛膝开发至关重要。申请人前期发现尖孢镰刀菌经固体发酵能100%的将20-羟基蜕皮甾酮转化为C19雄甾红苋甾酮，雄甾化合物药用价值远高于植物甾酮，并可作为甾体药物合成的关键中间体。基于此，本项目拟通过尖孢镰刀菌发酵改性土牛膝促进土牛膝开发，揭示尖孢镰刀菌发酵改性土牛膝的化学机制，探索该菌对土牛膝中甾体母核和三萜皂苷的影响，实现C19雄甾类化合物的富集及发现。通过酶抑制剂加入及发酵条件改变等方式，控制甾体侧链和母核降解，富集更多类型的甾体化合物，并对所得甾体化合物进行甾体相关活性筛选，包括抗炎、抗菌、抗肿瘤等。本项目的开展将为民族药滇产土牛膝的的开发提供一个新的思路，促进滇产土牛膝和甾体药物的开发，为发酵药材的研究和民族民间药的开发提供参考。

Fermentation study of Achyranthes aspera from Yunnnan with Fusarium oxysporum .Achyranthes aspera, a folk medicine of Bai nationality, is widely distributed in Yunnan Province. However, the development of this traditional Chinese medicine is very limited. A. aspera contains plenty of phytosterones, therefore, making good use of phytosterones in A. aspera is very important to the development of this folk medicine. Our previous study revealed that Fusarium oxysporum had the ability to facilitate the complete biotransformation of 20-hydroxyecdysone to C19 androstane compound rubrosterone by solid-state fermentation. Androstane compounds possess higher phamaceutical value than phytosterones and could serve as key intermediates for steroid drugs synthesis. Based on this, fermentation of A. aspera using F. oxysporum to facilitate the development of this folk medicine was proposed in the present study. The chemical mechanism of fermentation of A. aspera using F. oxysporum will be clarified. The influences of F. oxysporum on steroid stem nucleus and triterpenoid saponins in A. aspera will also be studied. Various androstane compounds will be available and some of them could be accumulated. According to adding enzyme inhibitor and changing fermentation conditions to control the degradation of side chain and stem nucleus of steroid and acquire various steroids. The bioactivities related to steroids will be tested, including anti-inflammatory, antibiosis and anti-tumor. This study will propose a new thought for the development of A. aspera in Yunnan Province, promote the discovery of androstane drugs, and facilitate the development of this folk medicine. Furthermore, the present project will provide a reference for the research and development of other folk medicines.