[Metabonomic study on the anti-liver injury effect of Si-Ni-San on rats by using UPLC-MS/MS].

A UPLC-MS/MS method based on metabonomic skills was developed to study the serum metabolic changes of rats after acute liver injury induced by CCl4 and to evaluate the action mechanism of Si-Ni-San. The integrated data were exported for principal components analysis (PCA) by using SIMCA-P software, in order to find the potential biomarkers. It showed that clear separation of healthy control group, model group, silymarin group, Si-Ni-San group was achieved by using the PCA method. Nine significantly changed metabolites were identified as potential biomarkers of acute liver injury. Compared with the health control group, the model group rats showed higher levels of phenylalanine, tryptophan and GCDCA together with lower levels of LPC 16 : 0, LPC 18 : 0, LPC 18 : 1, LPC 16 : 1, LPC 20 : 4 and LPC 22 : 6. These changes of serum metabolites suggested that the disorders of amino acid metabolism, lipid metabolism, bile acid biosynthesis and anti-oxidative damage were related to acute liver injury induced by CCl4. Si-Ni-San might have the anti-liver injury effect on all these four metabolic pathways.

Comparative pharmacokinetic study of four major components after oral administration of pure compounds, herbs and Si-Ni-San to rats.

The pharmacokinetic differences of paeoniflorin, naringin, naringenin and glycyrrhetinic acid (GA) following oral administration of pure compounds, single herbs and Si-Ni-San (SNS) decoction to rats were studied. Blood samples were analyzed with a validated UPLC-MS/MS method. Student's t-test was used for the statistical comparison. The Cmax and AUC0-∞ were 1470±434 ng/mL and 4663±916 ng h/mL for paeoniflorin, 64.29±59.21 ng/mL and 311.8±131.8 ng h/mL for naringin, 244.2±138.8 ng/mL and 4761±3167 ng h/mL for naringenin, and 1183±294 ng/mL and 38 994±14 377 ng h/mL for GA after oral administration of paeoniflorin, naringin and glycyrrhizic acid. The Cmax and AUC0-∞ were 812.6±259.6 ng/mL and 2489±817 ng h/mL for paeoniflorin, 344.3±234.9 ng/mL and 1479±531 ng h/mL for naringin, 981.9±465.4 ng/mL and 12 284±6378 ng h/mL for naringenin, and 3164±742 ng/mL and 78 817±16 707 ng h/mL for GA after oral administration of SNS decoction. There were significant differences between the pharmacokinetic behavior after oral administration of SNS decoction compared with pure components or herbs. The results indicated that some components in the other herbs of SNS had a pharmacokinetic interaction with paeoniflorin, naringin, naringenin and GA.