| Pachysandra terminalis Sieb. Zucc, the whole plant of Pachysandra terminalis (Buxaceae), is widely distributed in the southwest and northwest of the People’s Republic of China, as a Tujia traditional medicine against pain and stomach problems. Pachysandra terminalis also has the properties of reducing tussis, expelling wind and removing cold, promoting blood circulation to arrest pain. Mordern pharmacology research suggests Pachysandra terminalis has the activities of cytotoxic, anti-ulcer and exhibiting anticholinesterase activity.Phytochemical investigations of this species revealed the presence of several steroidal alkaloids as well as triterpenes and sterols. In recent years, a large number of steroidal alkaloids have been isolated from Pachysandra axillaries, Pachysandra procumbens, and species of the genus Sarcococca.Metastasis accounts for the majority of patients’deaths due to cancer, and thus cut off the metastatic process is of critical importance for cancer treatment, especially in late stage. Chemotaxis is one of the basic functions of cells, and directly participates in vital activities of immunological cell homing, neural development and so on. The latest researches show that chemotaxis plays critical role in cancer matastasis, and the main contribution to cancer metastasis arises from the failure of restriction in cancer cell migration. So, cell migration mediation-associated proteins are to be target of cancer metastasis treatment.Integrins are a family of heterodimers comprised of a and β subunits. Integrin (31combines with the a subunits to form12different integrin receptors, which bind extracellular matrix (ECM) molecules such as collagen and fibronectin. A large number of reports have shown that integrin β1is closely involved with cancer cell adhesion and metastasis.the protein kinase C (PKC) family, consisting of12serine/threonine kinases, can be divided into three subfamilies based on their activation mechanism. PKC plays pleiotropic roles in cell polarity, migration, and adhesion, and PKC ξ has been indicated to play an important role in determining cell polarity. Studies using isozyme-specific inhibitors suggest that PKC ξ is also involved in chemokine-triggered cell adhesion and actin assembly in polymorphonuclear cells, presumably mediated by G protein.The occurrence of steroidal alkaloids in Pachysandra is well documented, but little phytochemical work has been carried out on Pachysandra terminalis. In order to search the bioactive constituents from natural source, we began to study the chemical consitituents from Pachysandra terminalis. By repeated column chromatography, including Silica gel, Toyopearl HW-40and preparative HPLC,30compounds were isolated from extracts of Pachysandra terminalis. By using IR, MS,1H-NMR,13C-NMR,1H COSY, HMBC, HSQC, ROESY spectra and chemical methods, five new alkaloids,3β-(dimethylamino)-pregn-20a-ol-16-one (1),30-(dimethylamino)-pregn-16-one-5,17-diene (2),3β-(dimethylamino)-pregn-20a-ol-16-one-5-ene (3),20β-(dimethylamino)-3β-(senecioylamino)-5a-pregn-11α-ol-16-ene (4),20β-(dimethylamino)-3β-(senecioylamino)-5a-pregn-16-ene (5); along with25known compounds were identified.In the anti-tumor metastasis screening experiment of these compounds, alkaloids played a role in anti-tumor metastasis with both MDA-MB-231and A549cell lines. alkaloid compounds2,5,6-8,11-17, and19revealed significant anti-tumor metastasis activity, while they didn’t reveal cytotoxic acticity at that concentration. Western Blot analysis suggest that integrin β1and PKCξ may be key molecules in the signal transduction pathway targeted by these alkaloid compounds. |
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