Preparation Of Gypenosides And Secondary Gypenosides And Study Of Their Anti-hepatic Fibrosis Activity

Hepatic fibrosis is a pathological change in the development of chronic liver disease.It is mainly manifested as excessive proliferation and deposition of extracellular matrix in liver tissue,which leads to abnormal structural changes of liver tissue.Continuous onset of hepatic fibrosis would eventually turn into cirrhosis and even liver cancer.As the intermediate phase to irreversible cirrhosis and liver cancer,the process of hepatic fibrosis is reversible.Therefore,inhibiting or inversing the process is of great significance for the prevention of cirrhosis and liver cancer.Gynostemma pentaphyllum(Thunb.)Makino is a perennial climbing medicinal herb of the Cucurbitaceae,mainly distributed in tropical and subtropical areas of east Asia,such as south of the Qinling Mountains and Huaihe River in China,Korea,Japan,and Southeast Asia.Numerous studies have shown that gypenosides,the main active component of Gynostemma pentaphyllum,have significant liver protection effects.In recent years,research focus on the pharmacological activity of gypenosides has gradually shifted from gypenoside extracts to single gypenoside compound.Our previous study found that the gypenoside NPLC0393 can activate the protein serine/threonine phosphatase(PP2Cα)and showed good anti-hepatic fibrosis activity.NPLC0393 is a glycoside compound whose structure is composed of a dammarane-type tetracyclic triterpene aglycon and a polysaccharide side chain.The pharmacophore of NPLC0393 is still not clear,so it is necessary to further explore the structure-activity relationships of this gypenosides.In this thesis,thirteen natural gypenosides(1～13),including NPLC0393(1)and NPLC0394(2),were separated from a gynostemma extract collected in Ankang,Shanxi.Compounds 10～13 are new compounds with C20/C21/C23 configurations that have not been reported;compounds 8 and 9 were isolated from this plant for the first time.Based on the separation work,NPLC0394 were further used as a raw material to prepare the aglycon products(14,15)as well as the rare and trace secondary glycosides(16,17,18)through acid hydrolysis and enzymatic hydralyzation.Finally,the preliminary structural-activity relationships of above compounds against hepatic fibrosis were studied on cellular experiments.