Chemical, molecular and pharmacological assessment of Saussurea lappa Clarke

Saussurea lappa Clarke or Aucklandia lappa (Decne.) is a perennial herb of the genus Saussurea, family Compositae. It is an endangered species listed in Appendix I of the Convention on International Trade in Endangered species of Wild Fauna and Flora (CITES). Its dried root (Radix Saussurea, Muxiang), has long been used as traditional Chinese medicinal material for promoting the flow of qi and improving digestion by reinforcing the spleen function.; In the market, many substitutes and adulterants of S. lappa species have been found. Therefore, a reliable authentication of Muxaing species is necessary for the elimination of confused species, reducing the risk of misusing the medicine and conservation of the species.; In my study, chemical GC-MS fingerprint profiles have been constructed upon 28 Muxiang (Saussurea lappa and related species) samples. A high degree of separation and uniform peak distribution of chemical components have been determined with all the fingerprint profiles. Profile similarity and hierarchical clustering analysis provided sufficient information for sample classification.; ITS regions and 5S rRNA spacer domain were sequenced to perform molecular biological assessment of Saussurea lappa. The ITS regions and 5S spacer domain can be amplified by polymerase chain reaction (PCR). Sequence similarity analysis gave the clues for differentiating the variation of Saussurea lappa and other species.; Sesquiterpenoid constituents are the major active ingredients in Saussurea lappa. At the final part of my project, new pharmacological activities based on COX-2 inhibition were demonstrated. The active component, dehydrocostus lactone and costunolide were observed to interfere, independent of COX-1 inhibition, the formation of PGE2 synthesis at a concentration of 3.75muM, indicating them as COX-2 selective inhibitors. Further growth inhibition studies showed the two lactones inhibited the proliferation of a number of human cancer cell lines in vitro and induced apoptosis in a colorectal cancer cell line. Oral administration of the dehydrocostus lactone, at a dose of 5--30mg/kg/day, significantly attenuated the COLO 205 xenografted colon cancer and offered significant anti-inflammatory activity through inhibiting adjuvant-induced arthritis at a dose of 2--5mg/kg/day. Therefore these components from Saussurea lappa are potentially useful to treating cancer and inflammation.