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Studies On Chemical Constituents And Pharmacological Effect Of Active Fraction For Anti-Alzheimer's Disease In Valeriana Amurensis Smir .Ex Kom

Posted on:2008-01-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y M ZuoFull Text:PDF
GTID:1104360215960103Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Valeriana amurensis Smir.ex.Kom belongs to the genus Valerianal L.As.,a congener of which, jatamans valeriana rhizome (Valeriana jatamansi Jones), which is also called Saruma henryi, has been recorded in all past dynasties medicinal literatures, bitter in taste and frigidity. Valeric (valerian) is widely used as sedative in Europe and America. It is reported that Valeriana plays an important therapeuticaction role at nervous system, heart blood vessel of brain and resist tumour etc. It is recently discovered that Valeriana has a therapeutic role for nervous system degenerative diseases AD. In order to discover new medicinal plant, we studies Valeriana amurensis Smir.ex.Kom source of Daxinganling area of Heilongjiang Province on chemical constituents and pharmacological effect. In this study, the components obtained from the root and rhizomes of Valeriana amurensis Smir.exKom were elucidated. Besides, the pharmacological effect of the components on AD and their mechanisms of action were examined in vivo and in vitro.At first, using the model with multiple factors, we studies Valeriana amurensis Smir.ex.Kom of anti-AD from the aspects of apoptosis inflammation injury oxidative injury and the behavior experiments at cellar and molecular level. We identified the bioactive constituents from the 50% ethanol extract of the roots and rhizomes of Valeriana amurensis Smir.ex.Kom. The results showed that Valeriana amurensis Smir.ex.Kom improved the ability of the active and passive avoidance response and spatial recognization, the ability of learning and memoring; Valeriana amurensis Smir.ex.Kom pretects hippocampal neurous from the damage of free radicals by improving the activity of antioxidative enzyme CAT and decreasing MAO in rat's brain. Valeriana amurensis Smir.ex.Kom improves the pathologies tissue of rat's brain to normal level and accommodates the indexes of immunohistochemistry to normal level.In this study, the isolation procedure was carried out by column chromatography and HPLC; the structures of isolated compounds were identified by 1H-NMR, 13C-NMR, 1H-1HCOSY, HSQC, HMBC and ESI-MS. Isolation of the 50% ethanol extract of the roots and rhizomes of Valeriana amurensis Smir.ex.Kom afforded 29 constituents, including 2 iridoid compounds, 14 lignan compounds, 6 sesquiterpene compounds, 1 phenylmetholside, 2 phenethylalcoholsides and 4 other compounds, in which 6 sesquiterpene compounds were novel compounds and 16 compounds were firstly found in Valeriana amurensis Smir.ex.Kom. The structures of the six novel compounds were identified as heishuixiecao A[9-methyl-2,3-dime-thylmethylene-1 -acetoxy-5-aldehyde-8,9-epoxy-4(5)-cyclodecylene], heishuixiecao B[9-methyl-2,3-dimethylmethylene-1p-acetoxy-5-aldehyde-4(5),8(9)-cyclodecadi- ene], heishuixiecao C[9-methyl-2,3-dimethylmethylene-1α-acetoxy-5-aldehyde-4(5) ,8(9)-cyclodecadiene], heishuixiecao D[9-methyl-2,3-dimethylmethylene-1β-hydro-xy-5-aldehyde-4(5), 8(9)-cyclodecadiene], heishuixiecao E[2,3-dimethylmethylene-5-aldehyde-8β-hydroxy-9(14)-delta-4(5)-cyclodecylene], heishuixiecao F[2,3-dime-thylmethylene-5-aldehyde-8a-hydroxy-9(14)-delta-4(5) -cyclodecylene].Finally, Valeriana amurensis Smir.ex.Kom's pharmacological action of effective part and its chemical constituents were investigated in vitro, in order to test the reliability in vivo experiment and filtrate bioactive constituents of the pharmacological action of effective part. Meanwhile, we employed a pharmacological action of effective part research way in studying the Chinese medicine influence on the center nervous system, namely "Chinese medicine cerebrospinal fluid pharmacology". We use the cerebrospinal fluid with medicinal ingredient to study cell pharmacology, and combine the in vivo and in vitro experiment, further, we proved the effective substances for the treatment of AD. Moreover, in order to make the experiment condition more similar to the inside condition of inside body efficiency, the medicinal dosage of ten times was used outside body, further, we use pharmacological efficiency study of PC 12 cell of ice-dried cerebrospinal fluid. The result indicated that 50%EtOH elucidated part of valeriana amurensis Smir and separated three monomers equal vary degree' strengthen cell activity and inhibition cell fade, therefore, proved the effective substances for the treatment of AD.Based on study of the roots and rhizomes of Valeriana amurensis Smir.ex.Kom., the functional principle of efficient part of anti-AD was systematically elucidated, and the pharmacological effective substances of anti-AD of the roots and rhizomes of Valeriana amurensis Smir.ex.Kom, was proved from molecular level. We also provided an firmly base for further investigation using the Chinese medicine cerebrospinal fluid pharmacology that combines in vivo experiment with in vitro experiment. The advantages of Chinese medicine treatment with more pathways and efficiency were employed in this study. This study offers a science basis for studying new modern the Chinese medicine of anti-AD.
Keywords/Search Tags:Valeriana amurensis Smir.ex.Kom, Alzheimer's disease, constituents, pharmacological effect
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