Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.

Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon-telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.

Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis.

Recently, traditional Chinese medicine has gained attention for its potential use as a chemotherapeutic agent. Pseudolaric acid B (PAB) is a diterpene acid isolated from Pseudolarix kaempferi and possesses antifungal, antimicrobial, antifertility and antiangiogenic properties. It was also reported that PAB may inhibit proliferation and induce apoptosis in various types of cancer. However, its effects on A549 lung cancer cells remain to be determined. The present study aimed to determine the potential roles of PAB in the proliferation and apoptosis of A549 cells. The results showed that PAB inhibited A549 cell proliferation in a time­ and dose­dependent manner. Fluorescence microscopy results showed that cells treated with 20 µmol/l PAB for 24 h exhibited karyorrhexis and apoptotic body formation. In addition, A549 cells were treated with 5, 10, 20, 40 or 80 µmol/l PAB for 24 h and apoptosis was analyzed using Annexin­V/propidium iodide kit. The apoptosis rates were 8.95, 18.71, 24.66, 35.02 and 43.64%, respectively, in PAB­treated cells and 0.80% in the control group. Furthermore, western blot analysis showed that PAB treatment upregulated the protein levels of Bax, Bad and downregulated Bcl­2 and Bcl­xl expression. In conclusion, PAB may serve as a potent chemotherapeutic agent against human lung cancer.

Ultrasound-assisted extraction of phillyrin from Forsythia suspensa.

Forsythia suspensa (Thunb.) Vahl is one of the most widely used traditional Chinese medicines, and possesses important biological activities, such as antibacterial, antiviral, anti-inflammatory and antioxidant activities. Phillyrin is the main bioactive component of Forsythia suspensa. In this paper, ultrasound-assisted extraction of phillyrin from Forsythia suspensa was studied with HPLC-photodiode array detection. Effects of several experimental parameters, such as type and concentration of extracting solvent, ratio of liquid to material, extraction temperature, and time of sonication on extraction efficiencies of phillyrin from Forsythia suspensa were evaluated. The optimal extraction conditions were 1g plant sample with 10 ml of 20% methanol and the extraction for 60 min at 60°C under ultrasonic irradiation. Under the optimum conditions, the yield of phillyrin was 0.713±0.009 mg/g. The results indicated that the ultrasound-assisted extraction is a very useful method for the extraction of important phytochemicals from plant materials.

Preparation and evaluation of nicotinic acid sustained-release pellets combined with immediate release simvastatin.

This study was performed to prepare high-dose nicotinic acid (NA) loaded sustained-release pellets coated with double polymer and simvastatin (SIM). The uncoated pellets were prepared by extrusion-spheronization and the double ethylcellucose (EC) films were coated in a bottom-spray fluidized bed coater. SIM was milled by wet grinding and then the milled suspension was layered on the coated pellets. Results showed that coated with 1.5% subcoating and 1% outer coating composed of EC and polyvinyl pyrrolidone K30 (PVP(K30)) in ratios of 5:1 and 2:1, NA release behavior was very similar to the reference (NER/S; SIMCOR, Abbott) in different media. And SIM was delivered more rapidly than that of the reference, while the SIM layer had no influence on NA release. During 6-month storage at 40°C/75% RH, the two drugs exhibited stable dissolution behavior. It was observed that the content uniformity of SIM was provided by the present preparation and SIM was stable if adding light magnesium oxide in the grinding procedure. Results indicated it was possible to prepare high-dose sustained-release NA pellets combined with little-dose immediate release SIM by spraying double EC polymer and SIM milled suspension on NA pellets in a bottom-spray fluidized bed coater, respectively.