| Modern research shows that triterpenoid saponins glycyrrhizin has extensive pharmacological effects and is considered to be the main effect of substance of "detoxification". It has already been applied to the treatment of anti HBV liver injury in clinic. Further research has also confirmed that the activity of anti HBV liver injury of glycyrrhizin is related to nonspecific inhibition of multiple key targets of activity, including neuraminidase (NA, participation infection and replication of invirus), phospholipase A2 (PLA2, being relevant to stability of liver cell), and so on. But it is worth noting that licorice also contains complex triterpenoid saponins except for glycyrrhizin. However, as a result of the more polarity, similar structurel, as well as the difficulty in chemical separation and activity evalution, the research is mainly focused on glycyrrhizin and its chemical derivatives at home and abroad over the years. There were few reports on other natural triterpene saponins and their activity research. Based on basic theory of structure-activity relationship (SAR), we hypothesize that a series of licorice triterpenoid saponins also have similar anti-HBV activity of liver injury to glycyrrhizin, and the differences in the structure of these components will lead to the strength of different activities. The activity of some similar ingredients may be stronger than glycyrrhizin.In recent years, the focus at home and abroad mainly concentrated on Glycyrrhizin uralensis and its active relationship, therefore, this paper takes the Glycyrrhiza glabra as the research object, and the done work is as follows:1. Isolation and identification of licorice saponins monomer compounds:Total saponins are obtained by using polyamide and macroporous resin, and then passing over the C18 medium pressure column chromatography to obtain monomer compounds. Using UV, IR, MS, ID NMR,2DNMR and other modern technology as well as chemical method, the structure of 11 licorice saponins are identified, compound ST-1 (licorice saponin M3)、ST-2 (licorice saponin N4)、ST-3 (licorice saponin 04)、ST-4 (licorice saponin G2)、ST-5 (18a-licorice saponin G2)、ST-6 (macedonoside A)、ST-7 (29-hydroxyl-glycyrrhizin)、ST-8 (licorice saponin A3)、ST-9 (24-hydroxyl-licorice saponin A3)、ST-10 (22p-acetoxyl-glycyrrhizin) and ST-11 (glycyrrhizin), respectively. Among them, compounds ST-1～ST-3, natural triterpenoid saponins, are firstly separated from Glycyrrhiza. and enhance chemical components of licorice.2. The activity assessment and SAR of triterpenoid saponins monomer compound:To select key target protein (neuraminidase, phospholipase A2) concerning to anti-HBV liver injury, after that, using classic means to estimate the target protein activity, choosing the appropriate substrates, in the best reaction conditions, the activities of different components are observed on each target protein. Based on evaluation information of compounds, a computer simulation model is established to show a combination of component structure and target, as well as to explore SAR, forecast target affinity and discover the active substances. Results show that isolated triterpenoid saponins, due to the difference in substituents, such as type and position, along with space configuration, will lead to differet results. The difference in this activity has also been reflected on molecular docking, the reason might be that the site of action and the force of target proteins are not the same. Although the results can not match with synthetic drugs, the majority of diseases could not be affected by a single causative gene. According to the above results, the model between component structure and targets are established, to be used to explain the connotation of "multi components, multi targets and low affinity". This will open up a new world for the treatment of anti-HBV liver injury. |
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