Analysis And Evaluation Of Chemical Ingredients In Zingiber Officinale Roscoe And Silybin Derivatives

Analysis and Evaluation of Chemical Ingredients in Zingiber officinale Roscoe and Silybin DerivativesIt has become an important source of innovative medicines to discovery new drugs via natural products research.In this paper,based on preliminary work in our laboratory, the chemical constituents of Ginger from Luoping county of China's Yunnan Province were further studied,and the antioxidant activities and cell toxicity for 13 chemical constituents from ginger were evaluated.In addition,the antioxidant activities of 16 dehydrosilybin derivatives with structural modification were studied.1.Identification and biological activity evaluation of chemical constituents in Ginger, the rhizomes of Zingiber officinale Roscoe(Zingiberaceae),has a long history as a medicinal in the world and was also often listed in traditional Chinese medicine prescriptions.Ginger is mainly used for treatment of arthritis,rheumatism,vomiting, duodenal and gastric ulcers,sprains,muscle pain,pain,sore throat,constipation, indigestion,hypertension,senile dementia,fever,infectious diseases and worms diseases.Chemical studies of this plant species have led to the isolation and identification of numerous biologically active compounds such as gingerols,gingerones, shogaols and diarylheptanoids,etc.The diarylheptanoids,exhibiting a variety of biological activities including inhibition of the biosynthesis of prostaglandins and leukotrienes as well as antifungal,antioxidative,and cancer chemopreventive activities. Fourteen compounds were separated and purified by using chromatographic techniques from the MeOH extract of Z.officinale collected in Yunnan Province,Southwestern China.Three new diarylheptanoids,one new monoterpenoid,and other known diarylheptanoids were structurally identified by using NMR(¹H NMR,¹³C NMR and DEPT),MS(EI-MS,ESI-MS＆HR-ESI-MS),infrared spectrometry,elemental analysis,optical measurement,etc.The new compounds are reported as: 5-[4-hydroxy-6-(4-hydroxyphenethyl)tetrahydro-2H-pyran-2-yl]-3-methoxybenzene-1, 2-diol,sodium(E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3S-sulfonate, sodium(E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3R-sulfonate, hydroxycineole-10-O-β-D-glucopyranoside.The antioxidant activities of the isolated compounds in our laboratory were evaluated by the in vitro models of scavenging superoxide anion radicals and inhibiting the formation of lipid peroxides in liver microsomes.To investigate the antioxidant properties of these compounds under more physiological conditions,the compounds were further tested in a primary culture of hepatocytes isolated from rat liver against the oxidative damage of tert-butyl hydroperoxide.In order to evaluate the anticancer activity,the compounds were tested the cell toxicities on 9 cancer cell lines,including KB cell,BEL7404 cell,P388D1 cell,K562 cell,HL-60 cell,A549 cell,Hela cell,CNE cell,and PC-3 cell.Among the tested compounds,most of compounds exhibited strong superoxide anion radical scavenging activities in a phenazine methosulfate-NADH system.In a more biological system,these compounds were demonstrated to exhibit potent protection against lipid peroxidation in mouse liver microsomes exposed to oxidative conditions.These compounds were subsequently tested on primary cultures of rat hepatocytes exposed to oxidative damage,and definitive cytoprotective actions were found.The diarylheptanoids were found to possess potent antioxidant properties in all the above assays.On the other hand,most of these compounds did not possess any appreciable cytotoxiciy on cancer cells.2.Study on the antioxidant biological activity of dehydrosilybin derivatives2,3-Dehydrosilybin(DHS),a natural derivative of silybin which presents at very low concentrations in Silybum marianum(L) Gaertn.Not as silybin,DHS's biological research is very limited,partly because of its low yield and poor water-soluble(ie,less than the silybin).However,a recent report shows that DHS has a very strong antioxidant activity,its activity is higher than silybin.Therefore,our laboratory conducted a series of structural modification on the DHS.So the pharmacological activity of 16 DHS synthetic derivatives,as well as silybin and DHS has been studied in this thesis.The In vitro models used included 2,2-diphenyl-1-picrylhydrazyl(DPPH) and O₂^- free radical scavenging assays,and an inhibition test against LPO.The neuroprotective evaluation of the compounds against H₂O₂-induced toxicity of PC12 cells were performed in order to obtain more comprehensive information of the DHS derivatives' in vitro efficacy against neuronal injury caused by oxidative damage.We also use ferrous ions(Fe²⁺) chelating model to evaluate the biological nature of the DHS analogues to determine the different models DHS analogues in the treatment of AD and PD potential antioxidant activity.The study revealed that the more polar compounds, the di-ether at C7-OH and C20-OH as well as the mono-ether at C7-OH which possess aliphatic substituted acetamides,demonstrated excellent inhibition against LPO as well remarkable chelating potency on Fe²⁺ ions.Conversely,the di-allyl ether at C7-OH and C20-OH was more potent in protection of PC12 cells against H₂O₂-induced injury than DHS and quercetin.Overall,the more lipophilic alkenylated DHS analogs were better performing neuroprotective agents than the acetamidated derivatives.The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids,especially in neurodegenerative disorders such as Alzheimer's and Parkinson's disease.