Studies On The Chemical Constituents Of Hypericum Perforatum L. And Hypericum Scabrum L.

Hypericum perforatum L. and Hypericum scabrum L. are both species of the genus Hypericum of the Guttiferae family, which were collected from Xinjiang Uygur Autonomous Region. Because of their unique chemical compositions and a variety of pharmacological activity, study on this Hypericum has been a hot spot for the modern drug research in the pharmacological and phytochemical field.As part of a program to assess the chemical and biological diversity of several traditional Chinese medicines, this dissertation investigated chemical constituents of the aerial parts of Hypericum perforatum L. and Hypericum scabrum L., and bioactivities of different extracts and purified compounds on several pharmacological models with the help of pharmacological staff.By using various chromatographic techniques,32compounds have been isolated from an ethanolic extract of the aerial parts of Hypericum perforatum L. and their structures were elucidated by spectroscopic methods. Among them, two compounds were new (1,2*), including one phenolic compound (1*) and a flavonoid compound (2*). These compounds were divided into ten flavonoids (2,14-18,20-21,27-28), two xanthones (12,19), seven phenolic acids and their glycosides (1*,5-7,10,25-26), five terpenoids (3-4,22-24) and other types of compounds (31-32,13,29). Compound3,4,7,31were obtained from Hypericum for the first time and compound5,6was isolated from this plant for the first time. At a concentration of2μmol·L-1, compound8inhibited recombinant human PTP1B with inhibitory rate of96.4%and IC50of2.5μM. Five compounds (1*,3,4,9,16) may have NE reuptake inhibitory activity.In pursuit of another type of characteristic phloroglucinol components, which were not found in the research on H. perforatum, our study group have found39compounds from Petroleum ether extraction of aerial parts of H. scabrum, and identified38compounds, which included34polyprenylated phloroglucinols, two sesquiterpenes and two other kinds of compounds. Among them, compounds1-17*,19*-20*were new products,18*were new natural product, compounds1-6were simple phloroglucinols,8*and9were novel tricyclo [5.2.1] phloroglucinol compounds,10*and13*were unusual decarbon phloroglucinol components containing the ketal unit,14*was an unusual phloroglucinol component containing the spiro [4,5] unit,15*and17*were furan-phloroglucinols,7*was a pyran-phloroglucinol derivative,19*was a phloroglucinol containing oxygen bridge respectively, as well as a new sesquiterpene compound20*. A preliminary study to determine the stereochemistry of the CD spectra of phloroglucinol components was proposed. The feature of CD data [especially (3, y-unsaturated fragment of the CD data (near300nm)] provided a relatively easy way to determine the configuration for those compounds with similar structural units.In the in vitro assays, compound33(34) showed obvious [3H]-5-HT reuptake inhibitory activity. In the rat brain synaptosomes [3H]-NE uptake activity screening experiments, all kinds of crude extracts of H. scabrum exhibited significant NE reuptake inhibitory activity. The inhibition rates of18compounds (3*.9*,10*,11*,14*18*,23,25,26,27,28,30,32,33(34),36,37(38)) were all higher than80%. suggesting that these compounds inhibited remarkable NE reuptake inhibitory activity. In the10μM concentration compounds2*,5*,7*,8*,23,25,29,32,37(38) exhibited protective activity against a damage of hepatocyte, the survival rates were67%.77%,78%,73%,84%,94%,69%,80%,81%, with significance compared to the blank control group. The water part and the petroleum ether extraction showed potent cytotoxicity. However, purified compounds did not show significant cytotoxicity activity and PTP1B inhibition activity.