The Study Of Fermentation Of Rubus Chingi And Salvia Miltiorrhiza By Fungi

Fermentation, which has been gaining more and more attention recently, is an useful method for traditional Chinese medicine (TCM) processing. It is important to study the fermentation of TCM by microorganism.This thesis is composed of three chapters. In chapter 1, the recent progresses on the glycosylation of natural products by microorganism were reviewed. The related concepts, enzyme and reaction types of microbial transformation were included. Especially, the progresses on the glycosylation of different kinds of natural products, including flavonoids, phenolics, steroid, quinones, terpenes and alkaloids were reviewed.In chapter 2, the study on the fermentation of Rubus chingii with fungi was carried out. Rubus chingii is a plant belonging to the Rosaceae family and is extensively grown in both north and south China,also as a drug for thousands of years in traditional Chinese medicine to tonify the kidney, control nocturnal emissions and reduce urination. It was found that polyketides TMC 154 (1) and bionectriol A (2) were highly yield by the fermentation of Rubus chingii with Clonostachys rogersoniana. TMC 154 (1) and bionectriol A (2) exhibited various of biological activities, such as antimicrobial, anti-tumor activities and inhibitory effects on NO production. It is worthy to note that TMC 154 (1) exhibited broad spectrum anti-tumor activities and the effect was as equal as the positive control cis-dichlorodiamineplatinum. This thesis also studied the mechanism of the production of TMC 154 by C. rogersoniana, which found that arabinose was necessary for biosynthesis of TMC154. Moreover, the results of 14C isotopically tracer method verified that the arabitol in the molecular structure of TMC 154 was derived from arabinose in the culture medium. Besides, two compounds, including a new long chain unsaturated fatty acid clorogersine (3), were isolated and identified from the solid culture of C. rogersoniana, but no polyketoneh were obtained. This paper indicates some precursor or inducer in Rubus chingii promote polyketides produced by microorganism.In chapter 3, the study on the fermentation of Salvia miltiorrhiza (Danshen) with fungi was carried out. S. miltiorrhiza, which was listed in the Chinese Pharmacopeia, has long been used to treat cerebrovascular and cardiovascular diseases. Salvianolic acids, the main polyphenolic acids in S. miltiorrhiza, showeda variety of pharmacological activities, which have long stimulated scientists’strong interest. In the thesis, the antioxidant activities and total phenolic content (TPC) of fermented Salvia miltiorrhiza with 20 fungi were investigated, which revealed that G. luteus fermentation could significantly improve the antioxidant activity and TPC of S. miltiorrhiza. Subsequently, the main antioxidant constituents were characterized by spectroscopic analysis as salvianolic acids. HPLC quantification showed the enhanced content of salvianolic acid B after fermentation, which could be responsible for the improvement of antioxidant activity of S. miltiorrhiza after fermentation. The present study suggests that G. luteus fermentations were effective to salvianolic acids’enrichment process and the improvement process of antioxidant activity for S. miltiorrhiza. This paper explores a new method to utilize S. miltiorrhiza.