Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Oral administration of trace element magnesium significantly improving the cognition and locomotion in hepatic encephalopathy rats.

The therapeutic effects of iron, zinc and magnesium trace elements, as well as rifaximin were investigated and compared in HE rats. In this study, HE rats were treated with either ferrous sulfate (HE-Fe, 30 mg/kg/day), zinc sulfate (HE-Zn, 30 mg/kg/day), magnesium sulfate (HE-Mg, 50 mg/kg/day) or rifaximin (HE-Rf, 50 mg/kg/day), which was mixed with water and administered orally for 61 days. The Morris water maze (MWM) and open-field tests were used to evaluate cognitive and locomotor function. The blood ammonia levels before and after administration of the glutamine challenge test, manganese concentration and glutamine synthetase (GS) activity were measured. Significantly longer MWM escape latencies, less locomotor activity, higher blood ammonia levels, higher brain manganese concentrations and higher GS activity were observed in HE rats. However, HE-Mg and HE-Rf rats had significantly shorter MWM escape latencies, increased locomotor activity, lower blood ammonia, lower brain manganese concentrations and lower GS activity. Partial improvements were observed in HE-Fe and HE-Zn rats. The results indicated that oral administration of magnesium can significantly improve the cognitive and locomotor functions in HE rats by reducing the brain manganese concentration and regulating GS activity.

The immobilization of U(vi) on iron oxyhydroxides under various physicochemical conditions.

The immobilization of U(vi) at the solid-water interface is an important process affecting its transportation and migration in the environment, and is predominantly controlled by the sorption behavior of U(vi). In this study, U(vi) sorption on Fe(ii) and Fe(iii) oxyhydroxides prepared by a coprecipitation method was studied under a range of physicochemical conditions, including pH, ionic strength, presence of humic acid (HA) and temperature. The results showed that the sorption of U(vi) on iron oxyhydroxides is chemical, and that the principal rate limitation is due to intraparticle diffusion. The sorption of U(vi) on iron oxyhydroxides is strongly dependent on pH, but only weakly dependent on ionic strength through the entire pH range studied. Under acidic conditions, the presence of HA increases U(vi) sorption to a large degree, but an inhibiting effect on the sorption of U(vi) can be observed under alkaline conditions, due to the formation of soluble U(vi)-HA complexes. The sorption of U(vi) on iron oxyhydroxides is an endothermic process and favors high temperatures. The surface complexation model suggests three dominant monodentate inner-sphere complexes of [triple bond, length as m-dash]Fe(s)OUO2(+) (log K = 1.65), [triple bond, length as m-dash]Fe(w)OUO2OH(0) (log K = -8.00), and [triple bond, length as m-dash]Fe(w)OUO2(CO3)2(3-) (log K = 17.50), contributing to U(vi) sorption on iron oxyhydroxides over the entire observed pH range.

Effect of qi-tonifying and stasis-eliminating therapy on expression of vascular endothelial growth factor and its receptors Flt-1, Flk-1 in the brain of intracerebral hemorrhagic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects and mechanism of qi-tonifying and stasis-eliminating (QTSE) therapy on the expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the brains of intracerebral hemorrhagic (model) rats.</p><p><b>METHODS</b>One hundred and eighty Sprague-Dawley rats were randomly divided into six groups: the normal group (n=5), the sham-operative (SO) group (n=35), the model group (n=35), the QTSE group (n=35), the QT group (n=35) and the SE group (n=35). All the rats except those in the normal group and SO group were established into an intracerebral hemorrhage(ICH) model by intracerebral injection of collagenase type VII and the latter three were orally administered with Buyang Huanwu Decoction (a classical recipe for QTSE) or with some of its components for qi-tonification and for stasis-elimination, respectively. To the other three groups, normal saline solutions were given instead. Behavioral tests were carried out in the animals randomly chosen from each group on days 1, 2, 4, 7, 14, 21 and 28 after modeling. The expressions of VEGF, Flk-1 and Flt-1 were determined by immunohistochemistry and the number of vascular segments with positive expression in the injured brain area of the rats was calculated.</p><p><b>RESULTS</b>From day 7 onwards, the asymmetric forelimb use rate in the QTSE group recovered more significantly than that in the other model groups. In the model group, the expressions of VEGF, Flk-1 and Flt-1 appeared on day 1 and reached a peak on day 21, then weakened gradually. In the QTSE group, as compared with the other model groups, a higher level of VEGF expression was shown from day 7 (P<0.01) and a higher level of Flt-1 expression was shown from the 7th day to the 21st day (P<0.01).</p><p><b>CONCLUSION</b>QTSE therapy can up-regulate the expressions of VEGF and its receptors (Flk-1 and Flt-1) and improve the recovery of kinetic function in the ICH rats, which may be correlated with its action in modulating vascular regeneration to promote the reconstruction of microvascular networks in the damaged areas.</p>

Thinking on the assessment of clinical therapeutic effectiveness of TCM / 中国中西医结合杂志

How to assess the therapeutic effectiveness of TCM is the focus of this paper, the trend of study on standard for therapeutic effectiveness assessment and application of standard for disease combined with symptom diagnosis and treatment were described. Taking the study on standard for TCM syndrome of Gan as an example, the basic principle and existing problem in standard formulation were pointed out. The possibility in establishing the therapeutic effectiveness assessment system of TCM by using the quantified scale for therapeutic effectiveness assessment as a tool, i.e., the theoretical design of the scale formation should be in accord with the theories of TCM, and followed with scientific measuring principle, based on the sample investigation to establish the database of quantified scale, to make sure the scale that having corresponding checking process and scoring criteria so as to make the scale meeting the need of reliability and validity. It was also pointed owt that the scale should be used in combination with the standard for syndrome differentiation, thus, the scientific, practical therapeutic effectiveness assessment system of TCM could be built up.