Study On Chemical Modification Of The Enzyme Metabolite Of Ginsenoside And Its Antitumor Activity

Ginseng (the root of Panax ginseng C.A. Meyer), one kind of famous traditional medicine in China, Korea, Japan and some other Asian countries, is widely used as an oral administration drug for the treatment of diseases including cardiovascular and diabetic diseases. Recent pharmacological studies have identified the connections between ginseng intake and decrease incidence and growth of tumor. The major active component of ginseng are ginsenosides, which contain an aglycone protopanaxadiol or protopanaxatriol with a dammorane skeleton. Orally administered ginsenosides pass through the stomach and small intestine without decomosition by either gastric juice or liver enzyme, however it can be decomposed by intestinal bacterium and produce series of compounds. According to the result of new pharmacological studies, the compounds that absorbed into the blood and elaborated the antitumor effects isn't the ginsenosides but Ml, which can also be further biotransformed by the fatty acid esterification. The reaction products were EMI. hi a recent study, the researchers examined the antitumor activity of EMI in comparison with Ml and discovered that EMI possessed more antitumor activity. At the same time, the experimental result also indicated that the toxicity of EMI was lower and the retention time in the liver was longer than Ml, what's more, the results also showed that EMI has more effective antitumor activity and functions via the activation of immune responses compared with Ml. As a result, lengthened the existence in the body of human , EMI has more antitumor activity, and the mechanism of antitumor activity of EMI was through functions via the activations of immune responses . At present, researchers, both at home and abroad , get Ml, especially EMI from the metabolite of intestine or samples from animal's blood and liver after oral administration treatment, since the complicated method, difficult extraction, low yield rate etc., only a series of mixture of EMI were obtained, but not monomers ,so further studies on the structures and functions of EMI needed to be studied.Group of ginsenosides and monomer of ginsenosides are isolated by using phytochemistry method .According to the metabolic mechanism of intestinal bacterium to ginsenosides , the metabolic mechanism of enzyme to ginsenosides in vitro was studied . It also studied the pertinency of metabolic mechanism and coherency of metabolite between the metabolic mechanism of intestinal bacterium of ginsenosides and that of enzyme of ginsenosides in vitro .Moreover , introducing theory of metabolization of enzyme ,the metabolic mechanism of intestinal bacterium was redefined and explained .This accelerated the study in this field on molecular level . Based on the character of enzyme , specific enzyme which can metabolize Ml fromcharacteristics of the intestinal bacteria and enzymes, the author deduced that the enzymes secreted by intestinal bacteria take part in the metabolic processes not the intestinal bacteria. If these speculations confirmed, the study of metabolic mechanism of ginsenosides would have a reference value on the molecular level.With the help of HPLC (Agilent 1100), Ml and Rgs in the enzymlysis samples was determined . The result showed as following: the optimum enzymatic transformation rate of Ml and Rg3 were 8.36% and 2.58% respectively ..Temperature and time were main factors of this orthogonal experiment. optimum factor of metabolite Ml was: enzyme NS 44018, time lOdays and temperature 50. The transformation rate of ginsenoside-Re to metabolite Ml was 8.36%. While the transformation rate of ginsenoside Rgj was greatly influenced by the enzyme and time but slightly by the temperature,So the optimum condition enzyme of Rga was NS 44066, and time 1 day.Deferent enzymes have deferent optimal temperatures and action time and have quite high selectivity to chemical structures and sites of substrate . With the selection of specific enzyme to enzymlized the different ginsenosides, a lot of goal compounds might be obtained. The author has s...