Studies On The Chemical Constituents Of Isodon Excisoides (Sun Ex C.H.Hu) C.Y.Wu Et H.W.Li, And Their Anti-tumor Activity

Isodon plants contain many kinds of secondary metabolites, especially, ent-kaurane diterpenoids are main components. It is reported that these compounds have better bio-activity, such as cytotoxity activity, anti-oxidative activity, immunity adjust function, the activity toward cardiovascular system, anti-bacteria and anti-virus. Particularly its cytotoxity activity has been paid more attention by pharmacologists in the world.This study utilizes conventional screening method to screen the effective compounds from the polarity part of the alcohol extraction coming from the stems of Isodon excisoides, which distributed in zhangxian county of Gansu Province. Then several compounds were isolated from the extract using silica gel column elution assay. The evaluation of cytotoxic activity of 20 ent-kaurane diterpenoids against cell lines BEL-7402, HO-8910 and SGC-7901 was carried out by using sulphorhodamine (SRB) cellular protein staining assays, and their Structure-Activity Relationship(SAR) was studied.DNA damage caused by ent-kaurane diterpenoids WangzaozinA was detected by means of comet assay.The results as follows:1. Thirteen compounds were isolated from this plant, including seven ent-kaurane diterpenoids, three flavonoids, one triterpenoid and two steroids.2. According to the study of Structure-Activity Relationship(SAR), several kinds of structure of these ent-kaurane diterpenoids have different cytotoxity. The difference not only relates to the structure ofα-methylene cyclopentanone, but also relates to the other groups.3. The result exhibited that Wangzaozin A markedly inhibited the proliferation of SGC-7901 cells at low concentrations while made cells death at mass concentrations, and both in the time and dose-dependent manners. When SGC-7901 cells at higher concentrations, the morphologyof SGC-7901 cells' nuclei, observed by Giemsa staining, showedmorphological characteristics of apoptotic cells, revealing thatwangzaozin A could induce apoptosis in SGC-7901 cells.4. Using two different comet assay, obtained a basic conclusion thatWangzaozin A can't cause the damage of DNA directly. DNA fragmentof SGC-7901 cells may be caused by apoptosis induced by compoundWangzaozin A.