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Metabonomics Investigation On The Mechanisms Of Action Of Cantonese Herbal Tea

Posted on:2013-02-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:R YouFull Text:PDF
GTID:1114330374476411Subject:Sugar works
Abstract/Summary:PDF Full Text Request
As a typical representative of herbal teas, Cantonese Herbal Tea (CHT) is an aqueousextract of a mixture of medicinal plants with highly complex constitution. According toTraditional Chinese Medicine (TCM) theory, dietary intervention with CHT can detoxify anddrive sensations of heat and humidity from the body. Nowadays with the living standardsimproving, CHT is gaining more and more appreciation for health promotion and diseaseprevention. Considering relatively subtle and multifactorial effects of CHT interventions, theobserved modulations are hard to evaluate through traditional assessments. So CHT should beviewed as a whole system and be elaborated by rapidly developing metabonomics to producethe information of the effects of CHT on organisms and to pave the way to a better scientificevaluating system.With initial generation of multicomponent metabolic composition of biological fluids, cells,and tissues through various applications of high-throughout and highly sensitive analyticaltechniques and employment of advanced statistical and bioinformatic tools, metabonomicsaims at the comprehensive characterization of biological samples under certain conditions toprovide information on holistic metabonomic changes with relation to different stimulus, andthe interpretation of changes on metabolic pathways to decipher the physiological variation inthe whole organism. The metabolic phenotype is closely associated with real biological endpoints and provides a global systematic interpretation of biological effect under a particularset of conditions. Hitherto metabonomics has been found widespread applications in manyareas including diseases, drugs, nutrition and plant etc. Metabonomics focuses on the holisticmonitoring of real end-point metabolic changes in response to a xenobiotic intervention,which is coincident with TCM theory, and has the potential to be able to overcome theconfounding reasons and permit the study of the system-wide effects of CHT and provide anin-depth understanding of its mechanisms of action and health benefits.In this study, metabonomic approach was used to investigate the global biologicalcharacterization of rats following the intake of CHT and to understand the mechanisms ofaction of CHT. The main contents are as following: First, a1H NMR-based serum metabonomic approach was performed to analyze the rats'responses to consecutive CHT intake after10,20and30days and found that the metabolicresponses are different, illustrating that the metabolic responses are dynamic. For10-day CHTintake groups, no significant metabolic response was detected between dosed rats and normalrats, suggesting that the animals had no markedly responses to CHT or tried to maintainhomeostasis; while the metabonomic analysis for20-day groups showed that dosed rats wereapparently separated from control rats with the decrease in the glucose and lipoprotein leveland the elevation of glucogeneogenesis and a shift in energy metabolism from carbohydratemetabolism to lipid metabolism. The dosed rats still showed good separation from normal ratsafter30d intake of herbal tea with a notable decrease in pyruvate content with a consistentincrease in lactate content, and significant decreases in both lipoprotein and glucose contentshad been observed for30-day group, indicating that long-time ingestion of herbal tea maycause metabolic dysfunction.Secondly, urinary metabolic responses to CHT over time in rats were investigated during a38-day-period using GC-MS analytical technique and principal component analysis (PCA)and orthogonal projection on latent structures discriminant analysis (OPLS-DA) at each timepoint. The study revealed that repeated ingestion of CHT produced gradual and cumulativechanges in rats and many metabolic pathways were affected including those involving energymetabolism and amino acid metabolism and so on, but the change direction of which were notidentical during the ingestion period. OPLS-DA models were constructed to identifytime-dependent changes in metabolites related to CHT consumption by the comparison ofdoused rats to control rats at all sampling time points and found that the process could bedivided into two phases. In the first phase, the bioefficacy was characterized by elevatedantioxidant activity and the depletion of oxidative stresses. However, the effect was reducedwith time and replaced by a second phase characterized by the decreased flow of energymetabolism and an imbalance in gut microflora. If the first phases meant the perturbationunder normal range, the characteristics of lower flow of energy and gut microflora imbalancein the second phase suggested that the system metabonomic status deviated from normalrange, which can be viewed as negative metabolic effects as a result of long-termadministration of herbal tea. Thirdly, the protective effects of GHT on Shanghuo in restraint-stressed rats wasinvestigated by integrating serum and urinary GC/MS metabonomics. Serum and urinaryGC/MS profiling of rats exposed to14-day successive restraint stress for6h everydayrevealed dramatic changes as evidenced by downregulation of tryptophan metabolism, aminoacid metabolism, gut microflora imbalance and decreased energy flow. The administration ofCHT to restrain-stressed rats demonstrated that the protective effects of CHT on upregulationof energy metabolism, the recovery of gut microflora metabolism and the higher level ofanti-stressed abilities with the exception of elevation of antioxidant ability anddownregulation of cholesterol. But the lower tryptophan metabolism caused by restraint stresswas not recovered after intake of CHT, indicating that the CHT could not improve thedysfunction of the nervous system caused by restraint stress.
Keywords/Search Tags:CHT, metabonomics, NMR, GC-MS, restraint stress
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