Font Size: a A A

Studies On The Chemical Constituents Of Triterpenoid Saponins From The Fruits Of Panax Ginseng And Its Pharmacological Activities

Posted on:2008-12-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhaoFull Text:PDF
GTID:1104360212498024Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
In the thesis, base on the summary of the chemical constituents and its bioactivities about panax ginseng, panax quinquoflium and panax notoginseng, the Ginseng saponins of ginseng fruit(Jingyu, Jilin province), nootropic activities and mechanism of ginsenoside Re and its toxicities were studied. Panax ginseng C.A.Meyer is a kind of perennial herbage plant. Panax ginseng has long been used as a tonic in traditional Chinese medicine.Ginseng saponins are the main bioactive components. Ginseng fruit has plenty of ginseng saponins and its notable physiological active arose more and more interesting among the scholars all over the world. Our investigations focused on its chemical constituents and effects on nootropic action.Ginseng fruit juice was obtained by machinery compression after ginseng fruit thrown out seets, then purified via macroreticular adsorption resin (D101) and 95% ethanolic elution fraction was obtained. Ethanolic elution fraction was extracted by chloroform and n-butanol respectively. Ginseng fruit general saponins (GFGS) were acquired after n-butanol was evaporated.22 kinds of monomeric ginsenosides were acquired after GFGS separated and purified by column chromatography of silica gel,reversed phase silica column , semipreparative high performance liquid chromatography and recrystal methods. All of them were identified according their physico –chemical properties and spectrum analysis(MS, 1H-NMR, 13C-NMR, 2D- NMR,etc).They are ginsenoside L1(1),ginsenoside L2(2),CK(3),20(S) -protopanaxadiol(4),20(R)-protopanaxadiol (5),20(S)-ginsenoside-Rh2(6),20(R)-ginsenoside-Rh2(7),ginsenoside-Rb1(8),ginsenoside-Rb2(9),ginsenoside -Rd(10),ginsenoside-Rc(11),ginsenoside-Rb3(12),20(S)-ginsenoside-Rg3 (13),20(R)-ginsenoside-Rg3(14),20(S)-ginsenoside-Rh1(15),20(R)-ginsenoside -Rh1(16),20(S)-protopanaxatriol(17),20(R)-protopanaxatriol(18),ginsenoside-Re (19),ginsenoside-Rg1(20),20(S)-ginsenoside-Rg2(21),20(R)-ginsenoside-Rg2 (22), Both ginsenoside L1 and ginsenoside L2 are new ginsenosides obtained for the first time. They are 3-O-β-D-glucopyranosyl-dammara-20-deisohexyl -3β,12β,20-triol(1) and 3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl -dammara-20-ene-3β,12β,25-triol (2).For the first time we used many ethological tests on different age groups rats and kinds of memory obstacle models to illustrate that ginsenoside Re has beneficial effects in learning and memory. We adopted electropysiology method illustrated that Re can effective enhance LTP. We also demonstrate that ginsenoside Re is effective in antagonizing memory obstacle caused by nature caducity through morris water maze test in mice, step-through test in mice and morris water maze test in rat. The results indicated that ginsenoside Re has obvious nootropic activities, it could significantly improve attenuation of learning deficits due both to age and experimentally induced brain damage. Long-term potentiation (LTP) in the hippocampus is the key form of long-lasting synaptic plasticity that currently serve as primary experimental models of learning and memory formation in mammals,and LTP of evoked potentials in the hippocampus is a form of activity-dependent synaptic plasticity which has become widely regarded as a possible physiological substrate for some aspects of learning and memory. The result showed that ginsenoside Re (10-6M,10-7M,10-8M) could enhanced basic synaptic transmission in hippocampus dentate gyrus in rats. Ginsenoside Re's bioactivities in antagonizing memory obstacle caused by nature caducity and in learning deficits induced by Aβ25-35 and the mechanism of enhancing LTP are first discovery.The toxicity tests of ginsenoside Re were firstly studied, which providing a basic security evaluation for making the best use of ginsenoside Re in future.The results of acute toxicity tests of ginsenoside Re by oral administration in mice (5, 10g/kg) showed that no any animal dead and no abnormal signs observed. Toxicosis dosage of ginsenoside Re is more than 10g/kg in mice by oral administration. Further more the Beagle dogs are safe after oral ginsenoside Re below 7.5g/kg.The long-term toxicity test of Ginsenoside Re was given daily to SD rats for 182 days. The rats were divided into four groups at random, three ginsenoside Re groups according to oral administration dose of Re (38, 113, 375 mg/kg/day) and a control group. The results demonstrated that there was no abnormal alternation in body weigh change, behavious, haematological indexes, serum biochemistry values, visceral coefficient compared with the control group, and gross anatomy examined no abnormal pathological appearance on major organ compared with the control group.In summary, the 22 triterpenoid saponins in GFGS was studied, among them two new compounds ginsenoside L1 and ginsenoside L2. were found . Being the major compound in the amount and bioactivities of GFGS , ginsenoside Re was deeply studied in aspect of nootropic pharmacological action by means of ethological experiment, electrophysiology,at the same time the mechanism of ginsenoside Re on nootropic action was discussed.For the first time the security of ginsenoside Re was testified by systemic studies in both acute and long-term toxicity tests.Above results can be considered as the basis for the elucidation of the nootropic effect and clinical application of GFGS and ginsenoside Re.
Keywords/Search Tags:ginsenoside Re, ginsenoside L1, ginsenoside L2, learning and momory, nootropic action, toxicology test
PDF Full Text Request
Related items