OBJECTIVETo observe the clinical value of protoparaxotril saporlirs (PTS) combined with aspirin in the secondary prevention of cerebral infarction.

METHODSThe 140 patients with cerebral infarction were collected, among them the 120 patients during recovery stage were equally assigned to three groups by randomized, single blinded and open controlled principle, and they were treated respectively by PTS (A), aspirin (B), and PTS plus aspirin (C) for 6 months. The other 20, who couldn't or were unwilling to use aspirin, were arranged in group D for control. The platelet aggregation rate, incidence of stroke recurrence, gastrointestinal adverse reaction and the NIHSS scores of patients were observed during the six-month period of treatment.

RESULTSAs compared with group D, the lowering amplitude of platelet aggregation rate after treatment in the three treatment groups were significantly higher (P < 0.01). Comparison of platelet aggregation rate between group A and B showed significant difference after 3-month treatment (P < 0.05), but the difference became insignificant after 6-month treatment (P > 0.05). The incidence of stroke recurrence in the group A, B and C was 18.9%, 13.2% and 10.8% respectively, which showed no significant difference among them, but all were significantly lower than that in the group D (44.4%, P < 0.05). NIHSS scores in group A and C were significantly lower than in group B (P < 0.01); and the occurrence of gastrointestinal reaction was significantly lower in group A (P < 0.01).

CONCLUSIONLong-term application of PTS has the effects for preventing stroke recurrence, lowering gastrointestinal adverse reaction and improving patients' neural function in patients with stroke. As used in combination with aspirin, it shows potential practical importance in the clinical secondary prevention of stroke.

Aged ; Aged, 80 and over ; Aspirin ; administration & dosage ; adverse effects ; Cerebral Infarction ; drug therapy ; physiopathology ; prevention & control ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Sapogenins ; administration & dosage ; adverse effects ; Secondary Prevention

To study the pharmacokinetics of ginsenosides Rg1 and its metabolites after iv and oral administration in Wistar rats, the LC-MS/MS method was selected to determine ginsenosides Rg1 and its metabolites in plasma and their pharmacokinetic parameters were calculated. After oral administration of ginsenosides Rg1 to rats, ginsenosides Rg1, Rh1, F1 and protopanaxatriol (Ppt) could be detected in plasma. Their Tmax were 0.92, 3.64, 5.17, and 7.30 h, respectively; MRT were 2.68, 5.06, 6.65, and 5.33 h, respectively; AUC(o-t), were 2 363.5, 4 185.5, 3 774.3, and 396.2 ng x mL(-1) x h, respectively. After iv administration of ginsenosides Rg1 to rats, ginsenosides Rg1, Rh1 and FI could be detected in plasma. Their T1/2betaS were 3.12, 5.87, and 6.87 h, respectively; MRTs were 1.92, 5.99, and 7.13 h, respectively; AUCo-tS were 1 454.7, 597.5, and 805.6 ng x mL(-1) x h, respectively. So, it can be concluded that after oral administration, the amounts of metabolites were higher than the prototype in vivo, and the distribution and elimination of the metabolites were relatively slow. After iv administration, the amount of prototype were higher than that of the metabolites in vivo, and the distribution and elimination of the metabolites were relatively slow.
Administration, Oral ; Animals ; Area Under Curve ; Chromatography, Liquid ; Female ; Ginsenosides ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Injections, Intravenous ; Male ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Sapogenins ; blood ; Tandem Mass Spectrometry

In this study, the biopharmaceutical properties of 20 (S)-protopanaxadiol (PPD) were studied. Firstly, the equilibrium solubility and apparent oil/water partition coefficient of PPD were used to predict the absorption in vivo. Meanwhile the membrane permeability and absorption window were studied by Caco-2 cell model and single-pass intestinal perfusion model. Furthermore, the bioavailability and metabolism were combined to study the absorption properties and metabolic properties in vivo. All of them were used to provide theoretical and practical foundation for designing PPD preparation. The results showed that PPD is poorly water-soluble, and the equilibrium solubility in water is only 35.24 mg x L(-1). The oil-water partition coefficient is 46.21 (logP = 1.66). By Caco-2 cell model, the results showed PPD uptake in general, and it also has efflux. By in situ intestinal perfusion model, the results showed that the absorption of PPD in the intestine is good, and the effective permeability coefficient were duodenum > jejunum > ileum > colon. The oral bioavailability of PPD was 29.39%. It was not well. Metabolic studies showed PPD in vivo presented a wide spread metabolism. So the main factors that restricted oral bioavailability of PPD were the poor solubility and first-pass effect.
Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Caco-2 Cells ; Humans ; Intestinal Absorption ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley ; Sapogenins ; administration & dosage ; blood ; chemistry ; metabolism ; pharmacokinetics ; Solubility ; Tissue Distribution

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.
Animals ; Anti-Bacterial Agents ; pharmacology ; Biotransformation ; Chromatography, High Pressure Liquid ; Feces ; microbiology ; Gastrointestinal Microbiome ; drug effects ; physiology ; Ginsenosides ; blood ; Male ; Panax notoginseng ; chemistry ; Rats, Sprague-Dawley ; Sapogenins ; blood ; Saponins ; administration & dosage ; metabolism ; Tandem Mass Spectrometry

OBJECTIVETo establish a high-performance liquid chromatographic/tandem mass spectrometry (HPLC-MS/MS) method for determining 20(S)-protopanaxadiol (PPD) in rat plasma, in order to analyze pharmacokinetic characteristics of PPD and PPD cubic nanoparticles.

METHODSprague-Dawley rats were administered orally with PPD and PPD cubic nanoparticles, respectively. Their blood samples were obtained from fossa orbitalis at regular time points. The mobile phase was 0.05% formic acidac etonitrile-0.05% formic acidac water (95:5). Electrospray ionization (ESI) was adopted for the quadrupole tandem mass spectrum. SCAN mode was used for the quantitative analysis, with m/z 460. 4/425.3 and m/z 622.9/318.3 (Rh2, interior label) as secondary fragment ions. The concentration of PPD in plasma was analyzed. The concentration-time curve was mapped. The data were calculated by DAS program.

RESULTThe linearity of the PPD plasma concentration determination method ranged between 10-1 407 microg x L(-1), with the limit of quantification of 2.5 microg x L(-1). Both of the inter-day and intra-day precisions (RSD) were less than 13.25%, and the accuracy (relative error) was between +/- 8.50%.

CONCLUSIONThe method was so highly specific and sensitive with less plasma that it is suitable for pharmacokinetic studies. The prepared 20(S)-protopanaxadiol lipid cubic nanoparticles can enhance its absorption in vivo. Its relative bioavailability is 166% of the raw material.

Absorption ; Administration, Oral ; Animals ; Antidepressive Agents ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Chromatography, High Pressure Liquid ; methods ; Female ; Lipids ; administration & dosage ; blood ; pharmacokinetics ; Male ; Nanoparticles ; Rats ; Rats, Sprague-Dawley ; Sapogenins ; administration & dosage ; blood ; pharmacokinetics ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; methods ; Time Factors

This study was conducted to investigate whether administration of IH901, a ginseng intestinal metabolite, ameliorates exercise-induced oxidative stress while preserving antioxidant defense capability in rat skeletal muscles and lung. Eight adult male Sprague-Dawley rats per group were randomly assigned to the resting control, exercise control, resting with IH901 (25, 50, and 100 mg/kg) consumption (R/IH901), or exercise with IH901 (25, 50, and 100 mg/kg) consumption (E/IH901) group. The trained groups ran 35 min 2 days/week for 8 weeks. To analyze the IH901-training interaction, serum biochemical analysis, lipid peroxidation, citrate synthase, protein oxidation, antioxidant and superoxide dismutase in skeletal muscles and lung tissue were measured. Compared to the exercise control group, animals that consumed IH901 had significantly increased exercise endurance times (p < 0.05) and decreased plasma creatine kinase and lactate dehydrogenase levels (p < 0.05), while those in the E/IH901 groups had increased citrate synthase and anti-oxidant enzymes and decreased lipid peroxidation and protein oxidation (p < 0.05). In conclusion, IH901 consumption in aging rats after eccentric exercise has beneficial effects on anti-inflammatory and anti-oxidant activities through down-regulation of pro-inflammatory mediators, lipid peroxidation, and protein oxidation and up-regulation of anti-oxidant enzymes.
Aging ; Animals ; Antioxidants/administration & dosage/*pharmacology ; Dose-Response Relationship, Drug ; Lung/*drug effects/metabolism ; Male ; Muscle, Skeletal/*drug effects/metabolism ; Oxidative Stress/*drug effects ; Panax/chemistry ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Sapogenins/administration & dosage/blood/*metabolism/*pharmacology ; Specific Pathogen-Free Organisms