Penta-O-galloyl-β-D-glucose (PGG) In Dan Pi With Different Varieties And Different Processing Methods And Its Metabolism In Vivo

Cortex Moutan(Danpi in Chinese),the root bark of Paeonia suffruticosa Andrews(Paeoniaceae),is a well-known traditional herbal medicine for treating various diseases in China.There are a great variety of DanPi cultivars and several different processed Danpi in the current general market.The chemical composition is affected by several factors,penta-O-galloyl-β-D-glucose(PGG)is a tannin with the highest content and the most important anti-tumor bioactivity among more than 130 kinds of chemical constitutes in DanPi.The current researches on PGG are mainly focused on cell-level pharmacological studies,but there is little research on its distribution of PGG in Dan Pi with different varieties and different processing methods and its metabolism in vivo.In this thesis,analytical techniques such as nuclear magnetic resonance(NMR)and HPLC-Q-TOF-MS/MS were used to investigate PGG in DanPi,as the following three aspects:(1)To determine the distribution of PGG in Danpi,seven Moutan phenotypic cultivars with different colors were systematically analyzed using NMR-based metabolomics.A total of 16 metabolites from their methanol extracts were simultaneously identified and quantified.The quantitative data indicated the contents of PGG were higher in most of seven Danpi cultivars,especially the highest content obtained in "Zhaofen".The distribution of PGG was possibly attributed to the different physiological processes occurred in different tree peony cultivars.These results will provide the methodology of the distribution for other bioactive constitutes and a strong evidence for the quality assessment of Danpi.(2)"Zhaofen",one of Moutan cultivar,was processed into the peeled Cortex Moutan,the unpeeled Cortex Moutan and the sulfited Cortex Moutan based on different methods.The distribution of PGG in these processed Danpi samples was determined by HPLC and their antioxidant activity was evaluated by the DPPH radical scavenging method.The results showed that the peeled Cortex Moutan has the highest antioxidant activity,and the largest content of PGG,suggesting that the antioxidant activity of Danpi may be positively correlated with the content of PGG.These results formed a strong basis for the quality control and exploitation of Cortex Moutan.(3)The metabolites of PGG in rats were analyzed by HPLC-Q-TOF-MS.It was found that PGG had 10 metabolites in rat urine,3 metabolites in plasma,and 5 metabolites in feces.It is speculated that PGG is firstly metabolized to gallic acid in rats,then gallic acid undergoes sulfation,glucuronidation and methylation in rat liver to exert pharmacological activity and excrete out.These results will enhance the understanding of drug mechanism and metabolic pathway of PGG in vivo.In addition,Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxyl hydroxypropionate(IDHP)was a new drug candidate for anti-ischemic,HPLC-Q-TOF-MS was applied in analysizing the impurities of IDHP in this thesis.3 impurities were identified including oxazole ketone from raw material,Danshensu from reaction intermediates and methyl Danshensu from by-production.The study provides the important basis for quality control and clinical research of IDHP.