A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.

Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis.

Magnolol and honokiol, main active compounds from the bark of Magnolia officinalis, have been found to have various pharmacological actions, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties, without appreciable toxicity. Recently, the anti-tumor activity of magnolol and honokiol has been extensively investigated. Magnolol and honokiol were found to possess anti-tumor activity by targeting the apoptosis pathways, which have been considered as targets for cancer therapies. This review will focus on the mechanisms by which magnolol and honokiol act on apoptosis pathways in cancer that have been characterized thus far, including the death receptor mediated pathway, mitochondria-mediated pathway, caspase-mediated common pathway, and regulation of apoptosis-related proteins. These breakthrough findings may have important implications for targeted cancer therapy and modern applications of traditional Chinese medicine.

Establishment of a cell-based assay to screen insulin-like hypoglycemic drugs.

This study sought to establish a cell based assay to screen insulin analogs. Previous studies have proposed that up-regulation of glucose consumption may have the same anti-diabetic effects as insulin. Here, the amount of glucose that disappeared in culture medium after incubation with insulin or drugs was determined and served as an indicator of the glucose consumption of the cells. In order to establish a cellular model to screen insulin analogs, the sensitivities of four cell lines - BALB/c 3T3, HepG2, NIH3T3, and Bel7402 - to insulin were evaluated by detecting glucose consumption after incubation with insulin (0-125 nM) for 24 h. BALB/c 3T3 was more sensitive to insulin than the other three cell lines. Insulin elevated glucose consumption of BALB/c 3T3 in a concentrationand time- manner. Glucose consumption of BALB/c 3T3 increased by 30% after incubation with insulin (30 nM) for 24 h. Insulin increased the proliferation of BALB/c 3T3 at 48 h. A model was established by detecting glucose consumption after treating BALB/c 3T3 with drugs for 24 h. Using the cell-based assay, we screened more than two thousand samples from Traditional Chinese Medicine (TCM). Five extracts exhibiting glucose absorbance in medium were identified, indicating a hit rate of 0.5%. Results suggested that a cell-based assay by detection of glucose consumption in BALB/c 3T3 was suitable for high-throughput screening and was feasible to identify insulin-like hypoglycemic drugs. Five hits were discovered from natural products. Further characterization of these active extracts could help to identify potential anti-diabetic drugs.

[Protective effects of salvianolic acid A against impairment of memory induced by cerebral ischemia-reperfusion in mice].

In the present experiments, an impairment of memory model was made by cerebral ischemia-reperefusion in mice. Sal A at the dosage of 3 and 10 mg.kg-1 i.v. was shown to improve the impairment of memory function induced by cerebral ischemia-reperefusion in step down and step through tests. In these tests, the number of errors of Sal A treated group was less and the latency was longer than that of control group. Meanwhile, Sal A 3 and 10 mg.kg-1 i.v. was found to reduce the MDA contents in the cortex, hippocampus and striatum of cerebral ischemia-reperfused rats in vivo. Sal A 10-100 nmol.L-1 was shown to inhibit the brain lipid-peroxidation and scavenge the free hydroxyl radical in vitro. These results indicate that the antagonistic effects of Sal A on impairment of learning and memory caused by cerebral ischemia-reperefusion may be related with its anti-oxidant activity.

[Prevention of galactose-induced cataractogenesis in rats by salvianolic acid A].

Salvianolic acid A has been demonstrated to have efficient antioxidative and free radical scavenging effects. In the present experiments, the preventive effects of salvianolic acid A on galactose-induced cataract in rats were investigated. Dropping 0.05% salvianolic acid A in the eyes (two times a day) was found to delay the development of cataract. The contents of MDA and H2O2 in the cataract lens were decreased in salvianolic acid A treated rats. The protein and non-protein thiols in the cataract lens of the salvianolic acid A treated rats were higher than those of control rats. In in vitro experiments salvianolic acid A was shown to inhibit aldose reductase activity. These results indicate that salvianolic acid A can prevent galactose-induced cataract by antioxidation and inhibition of aldose reductase.