Studies On Bio-active Constituents Of Three Medicinal Plants

Screening bio-active nature products, clarifying material foundation of medicinaleffectiveness are the purpose of nature product research. China is rich in naturalmedicine resource, and traditional medicinal scriptures play a guide role on natureproduct research. In that case, three traditional medicinal plants, Aphanamixisgrandifolia Bl., Metasequoia glyptostroboides Hu et Cheng and Dracocephalumtanguticum Maxim., were selected for pharmacological and phytochemistryinvestigations.Part1: A. grandifoliaDetailed chemical investigation of the stems of A. grandifolia led to the isolationof60compounds by various chromatographic methods. The structure of53compounds were fully determined on the basis of spectroscopic analysis, includingtriterpenoids, sterols, sesquiterpenoids, apocarotenoids, isocoumarins, chromones,lignans, phenylpropanoids, dipeptides, et al. Among them,14compounds wereidentified as new compounds. AGB-1AGB-6were indentified to be the firstexample of2,3-seco-tirucallane triterpenoids. AGB-7was a novel triterpenoidsskeleton, which was formed on the basis of2,3ring opening and2,6ring closure.AGB-8AGB-10were the first reported3,4-seco tirucallane C29nortriterpenoids.The absolute structures of AGB-1, AGB-2and AGB-7were determined byX-ray crystal diffraction studies. The hypothetical biosynthetic routes of A-secotriterpenoids (AGB-1AGB-11) were shown in the thesis.The cytotoxic activities of38compounds isolated from A. grandifolia weretested in vitro against SKOV3, MGC-803, HCT-116and HepG2tumor cell lines withDOX as positive control. Some of them showed moderate to weak cytotoxicities.Principal component analysis was applied to ensure an objective interpretation of theoriginal cytotoxicity results of A-seco triterpenoids. The conclusions were arrived asbelow: The existence of ester group and epoxy group could enhance the cytotoxicactivity; The site of ring opening and the existence of24,25double bond could not affect the cytotoxic activity.Part2: M. glyptostroboidesBy detailed chemical investigations with various chromatographic methods,59compounds were isolated from the branches and stems of M. glyptostroboides. Theirstructures were fully determined on the basis of spectroscopic analysis, includingnorlignans, lignans, phenylpropanoids, apocarotenoids, flavan-3-ol derivatives,phenolic compounds, et al. Among them,5new compounds were identified,including three norlignans (MGH-3, MGH-4and MGH-11) and twophenylpropanoids (MGH-28and MGH-29).The hypothetical biosynthetic routes of three different frameworks of7-8'norlignans (MGH-1MGH-11) were shown in the thesis.From chemotaxonomic aspect, we supported the viewpoints that M.glyptostroboides should be established as a monotypic genus of Taxodiaceae family,and Metasequoia genus has close genetic relationship with Sequoia. Moreover, weconsidered that7-8' norlignans could be another specific marker of Taxodiaceaefamily beside biflavones. And the configuration of norlignans MGH-1MGH-5,which had only been found in M. glyptostroboides, might be considered as specificmarkers of M. glyptostroboides.The cytotoxic activities of43compounds isolated from M. glyptostroboides weretested in vitro against SKOV3and MGC-803tumor cell lines. Some of them showedmoderate to weak cytotoxicities.Part3: D. tanguticum22compounds were isolated and identified from the whole plant of D.tanguticum by various chromatographic methods and spectroscopic analysis,including flavonoids, phenylpropanoids, triterpenoids, sterols, et al. Among them,4compounds were identified as new compounds;4compounds were first isolated fromthe Dracocephalum genus; And4compounds were first isolated from this plant.17compounds isolated from D. tanguticum were tested for inhibitoryactivities against LPS-induced NO production in RAW264.7macrophages. Oneflavonoid compound showed moderate activity with no significant cytotoxicity.