Plasma metabonomics study of ischemic cerebral apoplexy rats treated with Tongsaimai pellets / 中国中药杂志

<p><b>OBJECTIVE</b>To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.</p><p><b>METHOD</b>Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.</p><p><b>RESULT</b>Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.</p><p><b>CONCLUSION</b>Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.</p>

Metabonomic phenotype of "formula corresponding to pattern types" based on "qi and yin deficiency pattern" of myocardial ischemia rat model / 药学学报

In order to explore the scientific connotation of "Fangzhengduiying (formula corresponding to pattern types)", "Qiyinliangxuzheng (Qi and Yin deficiency pattern)" of myocardial ischemia rat model and GC-TOF/MS based metabonomic method were used for comparing the effects of Sheng-mai injection, Salvia injection and propranolol in the present study. After data processing and pattern recognition, Sheng-mai injection showed better efficacy than the other two drugs in accordance with not only visual observation from PLS-DA scores plots but also the number of abnormal endogenous compounds restored to the normal level. Further studies showed that Sheng-mai injection could normalize the level of plasma endothelin-1, the index related to cardiovascular diseases and sleep disorders, which verified the results of metabonomics. Finally, the regulated metabolites and related metabolic pathways were analyzed, and it was supposed that the effects of Sheng-mai injection involved in the alternation of energy metabolism, lipid metabolism, amino acids metabolism, and so on. These findings provided scientific evidence to Shengmai "Fang" used for "Qi and Yin deficiency pattern" correspondingly, indicating that metabonomics has great potential in traditional Chinese medical research, which provides a novel approach and way to modernization of traditional Chinese medicine.

Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes.

The potential for herb-drug interactions has recently received greater attention worldwide, considering the fact that the use of herbal products becomes more and more widespread. The goal of this work was to examine the potential for the metabolism-based drug interaction arising from seven active components (danshensu, protocatechuic aldehyde, protocatechuic acid, salvianolic acid B, tanshinone I, tanshinone IIA, and cryptotanshinone) of danshen extract. Probe substrates of cytochrome P450 enzymes were incubated in human liver microsomes (HLMs) with or without each component of danshen extract. IC(50) and K(i) values were estimated, and the types of inhibition were determined. Among the seven components of danshen extract, tanshinone I, tanshinone IIA, and cryptotanshinone were potent competitive inhibitors of CYP1A2 (K(i) = 0.48, 1.0, and 0.45 microM, respectively); danshensu was a competitive inhibitor of CYP2C9 (K(i) = 35 microM), and cryptotanshinone was a moderate mixed-type inhibitor of CYP2C9 (K(i) = 8 microM); cryptotanshinone inhibited weakly and in mixed mode against CYP2D6 activity (K(i) = 68 microM), and tanshinone I was a weak inhibitor of CYP2D6 (IC(50) = 120 microM); and protocatechuic aldehyde was a weak inhibitor of CYP3A4 (IC(50) = 130 and 160 microM for midazolam and testosterone, respectively). These findings provided some useful information for safe and effective use of danshen preparations in clinical practice. Our data indicated that it was necessary to study the in vivo interactions between drugs and pharmaceuticals with danshen extract.