NMR Studies Of The Effects Of Phenolic Acids On Rodent’s Metabolome

Phenolic acids are widely present in plants and human daily diet. Study of the biological effects of phenolic acids will provide basic data for the usage of plant phenolic acids safely and properly. For most of the phenolic acids-consuming is attributed to the normal people, it’s more universal significant to study the biological effects of plant phenolic acids on healthy bodies, which was always ignored.In this thesis, we investigated the systematic changes of metabolic phenotypes of the body fluids and tissues in normal male Wistar rats with0.2%phenolic acid-enriched diet chronic intervention (including gallic acid, vanillic acid, caffeic acid, frulic acid and curcumin) with NMR-based metabonomics method combining with clinical serum biochemistry test and histopathology examination, and further explored the possible mechanism of phenolic acids actionFirstly, biochemical and metabolic alterations from the plasma and tissues after dietary intervention of101days showed that all the five kinds of compounds resulted in the decrease of serum alkaline phosphatase, but no change was observed in the liver histopathology examination. The degree of metabolic changes in tissues was different. The most significant metabolic changes occured in liver, followed with spleen, lung, kidney, muscle and thymus, respectively. To liver, phenolic acid-enriched dietary intervention promoted glycogenolysis, glycolysis, fatty acid β-oxidation, nucleotides catabolism and conversion from NAD to NMN; affected TCA cycle and choline metabolism; suppressed the conversion from xanthine to allantoin. Phenolic acids supplementation also promoted catabolism of proteins and nucleotides and fatty acid β-oxidation; suppressed the conversion to allantoin in the spleen. The metabolic disorders of carbohydrates, amino acids and nucleosides in the lung, kidney and muscle were also observed. These results may be attributed by oxidative stress induced by phenolic acids and their biological activities.Secondly, time-dependent effects on the plasma metabonome of the five phenolic acids were investigated. Results showed that the changed metabolites were inflammation and energy-related compounds such as OAG, glucose, creatine and so on. The results indicated that the phenolic acids could induce oxidative stress and lead to inflammatory response.Thirdly, the effects of the five phenolic acids on the dynamic metabolic changes of urine and feces were investigated. It was found that besides energy and amino acid metabolism, phenolic acids could also alter insoluble polysaccharide and proteinmetabolism in the gut. The reason might be ascribed to the disturbance of gut microbiota including the species and composition by these phenolic acids and their metabolites.Finally, the differences of metabolic responses induced by five phenolic acids were compared. It was found that ferulic acid affected the liver metabolome most actively, and the subsequent were gallic acid, caffeic acid, vanillic acid and curcumin, respectively. However, the metabolic alteration in the urine and feces was most obvious in curcumin group. These indicated that the degree of metabolic response induced by phenolic acids is not only related to their biological acivity, but also to the bioavailability.In a word, this thesis systematically investigated the metabolic responses of body fluids and tissues in rats to chronic phenolic acid-enriched diet intervention under no-observed-adverse-effect level (NOAEL), and it will provide some basic metabolic data for the future studies of phenolic acids. Furthermore, structure-activity relationship of five phenolic acids was also investigated using metabonomics method, expanding the application fields of metabonomics.