Metabolic profile of danshen in rats by HPLC-LTQ-Orbitrap mass spectrometry / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Danshen, the dried root of Salvia miltiorrhiza Bunge (Lamiaceae), is one of the traditional Chinese medicines (TCMs) most commonly used for the treatment of cardiovascular and cerebrovascular diseases. However, little is known about the chemical and metabolic profiles of danshen in vitro or in vivo. In particular, more information is needed in relation to the 50% ethanol extracts usually used in danshen formulations such as Fufang Xueshuantong Capsules and Fufang Danshen tablets. High-performance liquid chromatography coupled with a linear ion trap-Orbitrap mass spectrometer (HPLC-LTQ-Orbitrap) provides a sensitive and accurate method for analyzing the composition of samples. This method was used to determine the in vitro and in vivo chemical and metabolic profiles of danshen. Sixty-nine components of danshen extract and 118 components of danshen in rat plasma, urine, feces, and bile were unambiguously or tentatively identified. These results not only revealed the material composition of danshen, but also provided a comprehensive research approach for the identification of multi-constituents in TCMs.

Distribution of chemical compounds of Fufang Xueshuantong capsule in eyes and kidney of beagle dogs / 中国中药杂志

Diabetic retinopathy(DR) and diabetic nephropathy(DN) are the most common complications of diabetes, and the main causes of death and disability of diabetes. Clinical reports showed that Fufang Xueshuantong capsule(FXT) had effective curative effect on DR and DN, but there was no report on the distribution of chemical compounds of FXT in beagle dog eyes and kidneys. In this study, FXT was given by gavage administration in Beagle dogs for 3 days, and then their eyeballs and kidneys were taken. The chemical compounds in beagle dog eyes and kidneys were detected by HPLC LTQ-Orbitrap technology. Furthermore, by comparing with the data from retrieving literature and references, the chemical compounds were identified by the accurate mass, retention time (tR), and MS/MS. Fourteen and 19 types of notoginsenosides were respectively identified in eyeballs and kidneys in this study, and these results could lay foundation for clarifying the effective ingredients of FXT in treatment of DR and DN.

LC-LTQ-Orbitrap analysis on chemical constituents in Scrophulariae Radix extract and their metabolites in rat plasma / 中国中药杂志

Chemical constituents in extract of Scrophulariae Radix and their metabolites in rat plasma after oral administration were identified by HPLC-LTQ-Orbitrap. Samples were separated by a Venusil MP C₁₈ column using a binary gradient elution. The information on the total ion chromatogram, the extraction chromatogram and the mass spectrogram in a negative mode were synthetically analyzed by comparing the retention time, MS and MS/MS spectra with literature data and some of reference standards to conduct a qualitative study on constituents of Radix Scrophulariae extract in vivo and in vitro. Totally 37 compounds from Scrophularia ningpoensis extract were detected including 12 iridoid glycosides, 20 phenylpropanoids and 5 unknown compounds. In vivo, harpagide, harpagoside and angoroside C were confirmed to enter into the blood in prototype forms. Besides, another 2 prototype compounds and 2 metabolites were detected in rat plasma after oral administration of S. ningpoensis extract. The results are beneficial for the determination of bioactive substances of S. ningpoensis and significant for further studies on S. ningpoensis.

Phenanthrenes from aerial part of Juncus setchuensis with anxiolyticactivity / 中国中药杂志

Ten phenanthrenes, two organic acids, one organic acid ester and one flavonoid were isolated from the aerial part of Juncus setchuensis by various chromatographic techniques usingsilica gel, polyamide, Sephadex LH-20 as solid phases, and preparative HPLC. Their structures were identified by MS and NMR spectroscopic data as effusol(1), juncusol(2), juncuenin D(3), dehydroeffusol(4), dehydrojuncusol(5), juncuenin B(6),dehydrojuncuenin B(7), 2-methoxyl-7-hydroxyl-1-methyl-5-vinyl phenanthrene(8), 2-hydroxyl-7-carboxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene(9), 2-hydroxyl-7-carboxyl-1-methyl-5-vinylphenanthrene(10), luteolin(11), vanillic acid(12), daphnetin(13), p-coumaric acid(14), respectively. Compound 13 was isolated from the genus Juncus for the first time and compounds 5, 8-12 were isolated from J. setchuensis for the first time. The elevated plus-maze(EPM) was used to evaluate the anxiolytic activity of compounds 6 and 7. Compound 6 at 5 mg•kg⁻¹ and 10 mg•kg⁻¹ showed anxiolytic activity as well as compound 7 at 10 mg•kg⁻¹ and 20 mg•kg⁻¹.

Comparasion of the actions of human and porcine erythrocyte-derived depressing factor / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the action mechanisms of human and porcine derived erythrocyte-derived depressing factor (h-EDDF and p-EDDF) as well as the effects on blood pressure.</p><p><b>METHODS</b>The experiments were carried out in spontaneously hypertensive rats (SHR, n = 5) and two kidney-one click renal hypertensive rats (2K-1C, n = 7). The acute and chronic effects of h-EDDF and p-EDDF on blood pressure were observed, blood pressure test using tail plethysmography under unanaesthetic state. Both EDDF were administrated via jugular vein and/or oral respectively. The isolated thoracic aorta ring perfusion assay was used to examine the effect of EDDF on the asodilation. Primary cultured VSMCs were prepared from the thoracic aorta media of 2K-1C and normal Wistar rats. The effect of EDDF on proliferation of VSMCs were determined by MTT assay. The cell cycle of VSMCs was evaluated by flow cytometric.</p><p><b>RESULTS</b>Both h-EDDF and p-EDDF could significantly decrease blood pressure of Wistar rats through intravenous administration and/or orally (P < 0.01 and P < 0.05 respectively). The contractile response of aorta in 2K-1C rats to PE was significantly enhanced compared with that of the control (P < 0.01) and both EDDF (10(-3) g/ml) remarkably induced a vasodilation with endothelium-dependent manner in SHR and 2K-1C rats (P < 0.05). h-EDDF and p-EDDF could significantly inhibit the proliferation of VSMCs from 2K-1C and control rats. After 24 hours of exposure to EDDFs the cell number of G0/G1 phase obviously increased and cell number in S phase was decreased (P < 0.01, respectively).</p><p><b>CONCLUSIONS</b>It seems that the effects of h-EDDF and p-EDDF on blood pressure and vasodilation as well as inhibition of VSMCs proliferation and regulation of cell cycle have no significant difference.</p>

PHARMACOKINETIC STUDIES OF 20(R)-GINSENOSIDE RG3 IN HUMAN VOLUNTEERS / 药学学报

AIM　To study the pharmacokinetics of 20(R)-ginsenoside Rg3 (GRg3) in human. METHODS　High-performance liquid chromatography-ultraviolet detection method was used in this study. RESULTS　The pharmacokinetics of GRg3 in 14 healthy volunteers were investigated. After a single oral dose of 3.2 mg.kg-1 in 8 male volunteers, the plasma concentration-time course fitted well to a two-compartment open model, with the following pharmacokinetic parameters: Tmax (0.66±0.10) h, Cmax (16±6) ng.mL-1, T1/2α (0.46±0.12) h, T1/2β (4.9±1.1) h, T1/2(Ka) (0.28±0.04) h, AUC0-∞ (77±26) ng.mL-1.h. No kinetic analysis was made after an oral dose of 0.8 mg.kg-1 GRg3 in 6 other volunteers because of the low concentration, but a good correlation between Cmax and dosage of the two groups was found. CONCLUSION The absorption of GRg3 was rapid in man, and its elimination was rapid after oral administration of ginsenoside Rg3. The pharmacokinetic results shows that it exhibited first order kinetic characteristics.