Investigation of Evolution Rules of Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Ath- erosclerosis by NMR-based Metabolic Profiling and Metabonomic Approaches / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome.</p><p><b>METHODS</b>Totally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet. ED and XZD were used as drug probes. Blood samples were withdrawn at week 2, 4, and 8 after modeling. Blood lipids, blood rheology, histopathology and metabolomics were detected and analyzed. Results Results of blood lipids and pathology showed hyperlipidemia and early AS rat models were successfully established. At week 2 after modeling, levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) significantly increased, which reached the peak at week 4 and maintained at higher levels at week 8. ED exerted obvious effect in improving TC and LDL-C levels of early models, while XZD could greatly improve levels of TC and LDL-C of late models. Rheological results showed at week 2, there was no significant difference in whole blood viscosity, plasma viscosity, or hematocrit between the model group and the normal group (P > 0.05). At week 4 partial hemorheological indicators (such as plasma viscosity) were abnormal. Till week 8 whole blood viscosity, plasma viscosity, and hematocrit were significantly abnormal (P <0. 05, P < 0.01). As time went by, whole blood viscosity, plasma viscosity, and hematocrit showed gradual increasing tendency in the ED group, while they showed gradual decreasing tendency in the XZD group. Results of metabonomics showed significant difference in spectra of metabolites between the normal group and the model group. As modeling time was prolonged, contents of acetyl glucoprotein and glucose in the model group increased in late stage, which was in. line with results of blood lipids and hemorheology. ED showed more obvious effect in early and mid-term modeling (at week 2 and 4), and increased contents of partial metabolites (such as choline, phosphatidyl choline, glycerophosphocholine), but these changes in the XZD group were consistent with those of the model group. In late modeling (at week 8) XZD showed more obvious effect in improving contents of lactic acid, acetyl glycoprotein, LDL, creatine, choline, and glucose.</p><p><b>CONCLUSIONS</b>ED and XZD not only showed regulatory effects on lipid disorders, but also could improve dysbolism of Chos. In formulas corresponding to syndrome, damp-phlegm was main pathogenesis of hyperlipidema and AS in early and mid stages. Blood stasis syndrome began to occur along with it progressed. Phlegm can result in blood stasis and intermingles with stasis. Phlegm turbidity runs through the whole process.</p>

Comparative study on effects of Xiaoyao Powder and its modified prescription on plasma metabolomics of rats with chronic immobilization stress / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the changes in the levels of endogenous metabolites in rats with chronic immobilization stress (CIS) taking Xiaoyao Powder (XYP) and its modified prescription version, which lacks the volatile oils extracted from Herba Menthae.</p><p><b>METHODS</b>Twenty-four experimental male SD rats were randomly divided into 4 groups of 6 rats each: control, model, XYP-1 (containing volatile oils from Herba Menthae), and XYP-2 (lacking volatile oils). All rats except control group rats were subjected to CIS 3 h per day for 21 consecutive days. Groups XYP-1 and XYP-2 were given the extracted XYS with or without volatile oils (3.854 g/kg; suspended in distilled water) via gavage 1 h before CIS each day for 21 days. Rats were anesthetized using intraperitoneal injection of pentobarbital sodium (40 mg/kg) on the 22nd day. Observations were made using a Varian INOVA 600 MHz NMR spectrometer at 27 °C. Carr-Purcell-Meiboom-Gill (CPMG) and longitudinal eddy-delay (LED) were applied, resulting in spectra showing only the signals from micro- and macro-metabolites.</p><p><b>RESULTS</b>Compared to controls, rats subjected to CIS showed increased levels of plasma metabolites, such as acetic acid, choline, N-glycoprotein (NAC), saturated fatty acid, and blood sugars. Levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and unsaturated fatty acids were decreased. The biochemical effects of XYS were characterized by elevated levels of VLDL, LDL, threonine, methionine, and glutamic acid in plasma.</p><p><b>CONCLUSION</b>Some common and characteristic metabolites on the anti-CIS of XYP and its modified prescription were obtained. The metabolomics technology is a valuable tool and may be used to identify the specific metabolites and potential biomarkers of therapeutic effect of Chinese medicinal prescriptions.</p>

A(1)H NMR-based metabonomic study on the SAMP8 and SAMR1 mice and the effect of electro-acupuncture.

A (1)H NMR-based metabonomic method was used to investigate the metabolic change of plasma in senescence-prone 8 (SAMP8) mice before and after electro-acupuncture (EA). Sixteen SAMP8 male mice (aged 8 months) were randomly divided into model group and acupuncture treatment group while the later group received EA treatment for 21 days. Eight senescence-resistant 1 (SAMR1) mice were used as the control group. Morris water maze was used to evaluate the effects of EA. All mice plasma samples obtained from different groups were analyzed by using 600 MHz (1)H nuclear magnetic resonances ((1)H NMR) spectroscopy. The data sets were analyzed by Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA) to discriminate the key plasma metabolites among different groups. Results indicated that both the escape and probe tasks of SAMP8 could be improved by EA treatment. Metabonomic study showed that SAMR1 and SAMP8 were separated clearly in both CPMG_OSC_PLS and LED _OSC_PLS score plots. Interestingly, samples obtained from EA group were distributed closely to SAMR1 group in CPMG_OSC_PLS score plot, but away from SAMP8 group in LED_OSC_PLS score plot. Corresponding loading plots showed that much less lactate was seen in SAMP8 mice plasma. Other changes including higher levels of dimethylamine (DMA) Choline and α-glucose but lower levels of leucine/isoleucine, HDL, LDL/VLDL, 3-Hydroxybutyrate (3-HB), and Trimethylamine N-oxide (TMAO) were observed in the SAMP8 mice plasma than in the SAMR1. After EA treatment, the levels of lactate, DMA, choline and TMAO were improved. Results of this work can provide valuable clues to the understanding of the metabolic changes in the senile impairment of mice. It is also hoped that the methodology can be used in evaluating the effects of EA and understanding the underlying acupuncture mechanism in treating neurodegenerative diseases.