Anti-platelet aggregation of Panax notoginseng triol saponins by regulating GP1BA for ischemic stroke therapy.

BACKGROUND: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than 17 years due to its anti-platelet aggregation and neuro-protective effects, but its mechanism of action is not fully understand. In this study, anti-platelet aggregation-related protein analysis and computer simulations of drug-protein binding interactions were performed to explore the mechanism of the effects of PTS against ischemic stroke in an ischemia reperfusion model. METHODS: Three oral doses of PTS were administered in a model of middle cerebral artery occlusion (MCAO) in rats. Panax notoginseng total saponins (PNS) and a combination of PTS and aspirin were chosen for comparison. To evaluate therapeutic effects and explore possible mechanisms of anti-platelet aggregation, we measured cerebral infarct size and water content in brain tissue, histomorphological changes, expression of related factors (such as arachidonic acid metabolites) and platelet receptors in serum, as well as the binding affinity of PTS for platelet adhesion receptors. RESULTS: Compared with PNS, PTS showed a stronger and more potent anti-platelet aggregation effect in MCAO model rats. The combination of PTS and aspirin could reduce adverse gastrointestinal effects by regulating the TXA2/PGI2 ratio. We demonstrated for the first time that PTS was able to regulate Glycoprotein Ib-α (GP1BA) in a model animal. The binding of ginsenoside Rg1 and GP1BA could form a stable structure. Moreover, PTS could reduce von Willebrand factor (VWF)-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions. CONCLUSIONS: Our results showed that GP1BA was closely related to the anti-platelet aggregation action of PTS, which provided new scientific and molecular evidence for its clinical application.

Absolute Configurations and Bioactivities of Guaiane-Type Sesquiterpenoids Isolated from Pogostemon cablin.

Seven novel guaiane sesquiterpenoids (1-7) and three known seco-guaianes were isolated from the volatile oil of Pogostemon cablin. Their structures including absolute configurations were determined by spectroscopic analyses, a modified Mosher's method, and X-ray diffraction and ECD data. The results indicated that the ECD Cotton effects arising from one or two nonconjugated olefinic chromophores could be applied to define the absolute configurations of guaiane sesquiterpenoids. Compounds 3 and 6 exhibited significant vasorelaxant activity against phenylephrine-induced and KCl-induced contractions of rat aorta rings [half-maximal effective concentration (EC50) of 3 against PHE-induced contraction, 5.4 µM; EC50 of 6 against PHE- and KCl-induced contractions, 1.6 and 24.2 µM, respectively]. They also showed antifungal activity against Candida albicans (minimum inhibitory concentrations, 500 and 300 µM, respectively). In addition, 2 and 7-9 displayed a neuroprotective effect against glutamate-induced injury in PC12 cells.

Pocahemiketals A and B, two new hemiketals with unprecedented sesquiterpenoid skeletons from Pogostemon cablin.

Pocahemiketals A and B (1 and 2), two novel hemiketal sesquiterpenoids with unprecedented skeletons, were isolated from the essential oil of the aerial parts of Pogostemon cablin. In addition to a bicyclo[3.2.1]-carbon core, 1 and 2 possessed a hemiketal α,ß-unsaturated-γ-lactone moiety. Their structures were determined by extensive spectroscopic analysis, electronic circular dichroism calculation, and single-crystal X-ray diffraction. Compound 2 exhibited significant vasorelaxant activity against phenylephrine-induced contraction of a rat aorta ring with the EC50 value of 16.32µM.

[Study on constituents of the aerial parts of Pogostemon cablin].

OBJECTIVE: To investigate the chemical constituents of the aerial parts of Pogostemon cablin. METHODS: The constituents were isolated by column chromatography over silica gel, Sephadex LH-20 and C8. Structures were identified by spectroscopic data analysis. RESULTS: Thirteen compounds were obtained and elucidated as patchouli alcohol (1), pogostone (2), friedelin (3), epifriedelinol (4), oleanolic acid (5), methyl oleanolate (6), 5alpha-stigmast-3,6-dione (7), stigmast-4-ene-3-one (8), beta-sitosterol (9), pachypodol (10), retusin (11), (-)-guaiacylglycerol (12) and dibutyl phthalate (13). CONCLUSION: Compounds 6, 7, 8, 12 and 13 are isolated from this genus for the first time.

Hollow-bone-graft dynamic hip screw can fix and promote bone union after femoral neck fracture: an experimental research.

BACKGROUND: Delayed bone union, nonunion or osteonecrosis often occur after femoral neck fractures in young adults. Secondary bone healing requires strong internal fixation, intramedullary pressure reduction and early functional exercise. OBJECTIVE: To compare bone healing of femoral neck fractures treated with hollow-bone-graft dynamic hip screws (Hb-DHS) and standard dynamic hip screws (DHS) in an animal model. DESIGN: Testing of specifically designed fixation devices in a pig animal model. INTERVENTIONS/METHODS: We designed Hb-DHS and DHS devices appropriate to the femoral neck and head of experimental animals and used them in eight pigs (4-month-old, male or female, 30-40 kg/each). Under anesthesia, we induced medium neck type, Garden III type femoral neck fractures in each pig with fracture gaps of 0.5 mm and then fixed each left femur with Hb-DHS and each right femur with DHS. We assessed the animals radiographically and by postmortem visual appraisal of evidence of bone healing 8 and 16 weeks postoperatively. RESULTS: There were significant differences in radiographic and general findings between the Hb-DHS and DHS groups at weeks 8 and 16 postoperatively. We found statistically significant differences between the Hb-DHS and DHS groups in bone healing scores, trabecular bone volume percentage and bone mineral density as assessed on plain radiographs and computed tomography images (P < 0.05). There were also significant differences between the Hb-DHS and DHS groups in postmortem visually assessed indicators of bone healing at both 8 and 16 weeks postoperatively. CONCLUSIONS: The Hb-DHS device promotes femoral neck bone union, stimulates trabecular bone formation, increases BMD and has advantages over DHS for internal fixation of femoral neck fractures. This animal experiment will contribute to developing optimal treatment for femoral neck fractures in young adults.

Rap system of stress stimulation can promote bone union after lower tibial bone fracture: a clinical research.

BACKGROUND: Lower tibial bone fracture may easily cause bone delayed union or nonunion because of lacking of dynamic mechanical load. OBJECTIVE: Research Group would design a new instrument as Rap System of Stress Stimulation (RSSS) to provide dynamic mechanical load which would promote lower tibial bone union postoperatively. METHODS: This clinical research was conducted from January 2008 to December 2010, 92 patients(male 61/female 31, age 16-70 years, mean 36.3 years) who suffered lower tibial bone closed fracture were given intramedullary nail fixation and randomly averagely separated into experimental group and control group(according to the successively order when patients went for the admission procedure). Then researchers analysed the clinical healing time, full weight bearing time, VAS (Visual Analogue Scales) score and callus growth score of Lane-Sandhu in 3,6,12 months postoperatively. The delayed union and nonunion rates were compared at 6 and 12 months separately. RESULTS: All the 92 patients had been followed up (mean 14 months). Clinical bone healing time in experimental group was 88.78±8.80 days but control group was 107.91±9.03 days. Full weight bearing time in experimental group was 94.07±9.81 days but control group was 113.24±13.37 days respectively (P<0.05). The delayed union rate in 6 months was 4.3% in experimental group but 10.9% in control group(P<0.05). The nonunion rate in 12 months was 6.5% in experimental group but 19.6% in control group(P<0.05). In 3, 6, 12 months postoperatively, VAS score and Lane-Sandhu score in experimental group had more significantly difference than them in control group. CONCLUSIONS: RSSS can intermittently provide dynamic mechanical load and stimulate callus formation, promote lower tibial bone union, reduce bone delayed union or nonunion rate. It is an adjuvant therapy for promoting bone union after lower tibial bone fracture.

Effects of a sliding plate on morphology of the epiphyseal plate in goat distal femur.

The aim of this study was to observe the effects of a sliding plate on the morphology of the epiphyseal plate in goat distal femur. Eighteen premature female goats were divided randomly into sliding plate, regular plate and control groups. Radiographic analysis and histological staining were performed to evaluate the development of epiphyseal plate at 4 and 8 weeks after surgery. In the sliding plate group, the plate extended accordingly as the epiphyseal plate grows, and the epiphyseal morphology was kept essential normal. However, the phenomenon of the epiphyseal growth retardation and premature closure were very common in the regular plate group. In addition, the sliding plate group exhibited more normal histologic features and Safranin O staining compared to the regular plate group. Our results suggest that the sliding plate can provide reliable internal fixation of epiphyseal fracture without inhibiting epiphyseal growth.

[Transpedicular intracorporeal hydroxyapatite grafting and pedicle screw fixation via paraspinal approach for thoracolumbar fractures].

OBJECTIVE: To investigate the feasibility and safety of the treatment for thoracolumbar fractures with transpedicular intracorporeal hydroxyapatite grafting and pedicle screw fixation via paraspinal approach. METHODS: From June 2007 to December 2008, 19 cases of thoracolumbar fractures were treated with transpedicular intracorporeal hydroxyapatite grafting and pedicle screw fixation via paraspinal approach. There were 7 female and 12 male, ranging from 21 to 57 years of age (mean 40.8 years) at surgery. The time from injury to surgery varied from 1 d to 5 d (mean 2.9 d). Nineteen patients all suffered from single thoracolumbar fracture with the distribution of injury level being T(11) in 1, T(12) in 5, L(1) in 9, and L(2) in 4. According to Denis fracture classification, there were 5 compression fractures and 14 burst fractures. The mean preoperative ratio of the anterior height of the body was 57.2%, kyphosis angle was 17.6° and occupation of spinal canal was 27.7%. The mean preoperative load-sharing classification of spine fractures was 5.2. Based on the ASIA neurologic grading system, preoperative neurological function was grade B in 2 cases, C in 9 and D in 8. RESULTS: Median operating time was 83.8 min (range 60-95 min) and median blood loss was 133 ml (range 90 - 200 ml). Infection did not occur in any of the patients and the operative incisions were healing well. Average follow-up time was 19.2 months (range 12 - 36 months). At the latest follow-up, the height of the anterior border was corrected to 88.4%, the kyphosis angle was 6.1°, and the occupation of spinal canal was 8.2% on average. The postoperative neurologic function of all 19 patients was improved with grade D in 2 cases and E in 17. There were no instances of instrumentation failure and no patient had persistent postoperative back pain. CONCLUSIONS: Transpedicular intracorporeal hydroxyapatite grafting and pedicle screw fixation via paraspinal approach could provide reliable neurologic improvement in patients with incomplete neurologic deficit, and could prevent the development of kyphosis.Furthermore, it has the obvious advantages of less invasive and blood loss, and decreases the risks of postoperative lumbodorsal pain.