| Sini decoction (SND) is a well-known Traditional Chinese Medicine (TCM) formularecorded in Treatise on Febrile Diseases (Shanghan Lun), composed of Acontiumcarmichaeli, Glycyrrhiza uralensis and Zingiber officinale. It can recuperate the depletedyang and rescue the patients from danger. Recent research showed that SND was aneffective prescription in the treatment of cardiovascular disease. This paper studied SNDby combining chemomics with metabonomics. The aim of this paper was to systematicallydiscuss the chemical substances and mechanism of SND, and to offer the reference oftechnology for related investigation of other TCM formula.An HPLC-DAD-TOFMS method was applied to separation and identification ofcompounds in SND and rat plasma after oral administration. With dynamic adjustment offragmentor voltage in TOFMS and database matching,53compounds including24aconitum alkaloids,12flavonoids,13triterpene saponins and4gingerol-related wereidentified in SND. After oral administration of SND,38compounds including33absorbedcomponents and5potential metabolites in rat plasma were detected and identified bycomparing and contrasting the compounds measured in SND with those in the plasmasamples by HPLC-TOFMS. The result was an offer of assistance for the metabolism andcurative mechanism study of SND.We developed a method based on UHPLC-DAD and UHPLC-Q-TOFMS as well asMultiple Statistical Analysis technique, which could be applied in screening andidentification of TCM xenometabolome in vivo. Based on this method,102xeno-metabolites of SND were screened and identified in rat urine, including53parentcomponents and49potential metabolites. It was found that hydrolysis andO-demethylation are the major biotransformation pathways of aconitum alkaloids in vivo,and also found that the main metabolic pathways of flavonoids were glucuronidation,sulfation, reduction, demethylation and hydroxylation. This method could be considered asan important tool for rapid characterization of TCM xenometabolome in vivo.A tissue-targeted metabonomic method using GC-MS was developed to characterize themetabolic profile of DOX-induced cardiomyopathy in mice. It was confirmed that SNDhas satisfactory effect on DOX-induced cardiomyopathy from the regulation pattern ofmetabolites. SND administration could provide satisfactory effect on DOX-induced cardiomyopathy through partially regulating the perturbed metabolic pathways includinginvolving glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism,which could help us to elucidate the mechanism of SND in protect DOX-inducedcardiomyopathy.A metabonomic approach based on both RPLC-Q-TOFMS and HILIC-Q-TOFMS hasbeen developed to characterize the global serum metabolic profile associated withmyocardial infarction (MI) and investigate the intervention mechanisms of SND.Twenty-one potential biomarkers have been identified as being primarily involved insphingolipid metabolism, phospholipid catabolism, fatty acid transportation andmetabolism and tryptophan metabolism pathways. The results demonstrated that SNDadministration could provide satisfactory effects on MI through partially regulating theperturbed metabolic pathways.A urinary metabonomic method based on nuclear magnetic resonance and ultrahigh-performance liquid chromatography coupled to mass spectrometry was developed tocharacterize MI-related metabolic profiles and delineate the effect of SND on MI. Nineteenpotential biomarkers in rat urine were screened out, primarily related to myocardial energymetabolism, including the glycolysis, citrate cycle, amino acid metabolism, purinemetabolism and pyrimidine metabolism. With the altered metabolism pathways as possibledrug targets, we systematically analyze the therapeutic effect of SND, which demonstratedthat SND administration could provide satisfactory effect on MI through partiallyregulating the perturbed myocardial energy metabolism. It provided a new methodologicalcue for studying the holistic efficacy of the other TCM formulae.
|
PDF Full Text Request