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Microglia-mediated neuroinflammation plays a crucial role in the pathophysiological process of multiple neurological disorders such as ischemic stroke, yet lacks effective therapeutic agents. Previously, we discovered one novel synthetic compound, tanshinol borneol ester (DBZ), possesses anti-inflammatory and anti-atherosclerotic activities, whereas little is known about its effects in CNS. Therefore, the present study aims to explore the effects and potential mechanism of DBZ on neuroinflammation and microglial function. Our studies revealed that DBZ significantly inhibited NF-κB activity, suppressed the production of pro-inflammatory mediators meanwhile promoted M2 mediators expression in LPS-stimulated BV2 cells and mouse primary microglia cells. DBZ also exhibited antioxidant activity by enhancing Nrf2 nuclear accumulation and transcriptional activity, increasing HO-1 and NQO1 expression, and inhibiting LPS-induced ROS generation in BV2 cells. Importantly, the anti-neuroinflammatory and antioxidant effects of DBZ above were reversed by Nrf2 knockdown. Additionally, DBZ ameliorated sickness behaviors of neuroinflammatory mice induced by systemic LPS administration, and significantly reduced infract volume, improved sensorimotor and cognitive function in rats subjected to transient middle cerebral artery occlusion (tMCAO); besides, DBZ restored microglia morphological alterations and shifted the M1/M2 polarization in both murine models. Mechanistically, DBZ-induced Nrf2 nuclear accumulation and antioxidant enzymes expression were accompanied by increased level of p-Akt(Ser473) (activation) and p-GSK3β(Ser9) (inactivation), and decreased nuclear level of Fyn both in vitro and in vivo . Pharmacologically inhibiting PI3K or activating GSK3β markedly increased nuclear density of Fyn in microglia cells, which blocked the promoting effect of DBZ on Nrf2 nuclear accumulation and its antioxidant and anti-neuroinflammatory activities. Collectively, these results indicated the effects of DBZ on microglia-mediated neuroinflammation were strongly associated with the nuclear accumulation and stabilization of Nrf2 via the Akt(Ser473)/GSK3β(Ser9)/Fyn pathway. With anti-neuroinflammatory and antioxidant properties, DBZ could be a promising new drug candidate for prevention and/or treatment of cerebral ischemia and other neuroinflammatory disorders.

Plants from the genus Sanguisorba have been treated as medicinal ingredients for over 2000 years. This paper reviews advances in the botanical, phytochemical and pharmacological studies of the genus. To date, more than 120 chemical constituents have been isolated and identified from these plants, especially from S. officinalis and S. minor. Among these compounds, triterpenoids, phenols and flavonoids are the primary biologically active constituents. Triterpenoids can be used as quality control markers to determine the quality of medicinal materials and their preparations. In vivo and in vitro studies have shown that plants from the genus Sanguisorba exhibit a wide range of pharmacological properties, including hemostatic, antibacterial, antitumor, neuroprotective and hypoglycemic activities. In Chinese medical practice, many drugs (e.g., tablets and powders) that contain S. officinalis roots have been used to treat leukopenia, hemorrhaging and burns. However, there is still a multitude of Sanguisorba species that have garnered little or no attention. Indeed, there are few reports concerning the clinical use and toxic effects of these plants. Further attention should be focused on the study of these species in order to gather information on their respective toxicology data, any relevant quality-control measures, and the clinical value of the crude extracts, active compounds, and bioactive metabolites from Genus Sanguisorba.

Imatinib and its analogues were successfully synthesized by an improved method in 19.5-46.2% total yield of six main steps. Pyrimidinyl amine was prepared by the reaction of enaminone and guanidine nitrate without the use of a toxic cyanamide. N-(2-Methyl-5-nitrophenyl)-4-(pyridin-3-yl) pyrimidin-2-amine as a key intermediate for the synthesis of imatinib was prepared by coppercatalyzed N-arylation of heteroarylamine in 82% yield. The copper salts were used instead of the expensive palladium compounds in this C-N bond-forming reaction. The intermediate nitro compound was reduced by a N 2 H 4 • H 2 O/FeCl 3 /C system using water as a solvent in good yield.

Simple and inexpensive copper‐mediated N‐arylation ofheteroarylamines was achieved by using N,N′‐dimethylethylenediamine as a ligand and K2CO3 as a base in dioxane heated at 100 °C. In this coupling reaction, the influence of the copper species, ligand, base and solvent was investigated in detail. N‐Arylated derivatives of several heteroarylamines were synthesized under optimized reaction conditions, and all the products were isolated in good yields. By controlling the amount of CuI/DMEDA added, heteroarylamines with weak nucleophilic activity were coupled with aryl iodides or aryl bromides. The activity of the copper catalyst for this C–N bond‐forming reaction follows the order CuI > Cu0 > CuII. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

In this study, we tested the performance and biocompatibility of a composite of β-tricalcium phosphate (β-TCP) to collagen as a bone void filler (Cerasorb(®) Ortho Foam) in a rabbit distal femoral condyle model. β-TCP is a completely resorbable synthetic calcium phosphate and the addition of a collagen matrix couples the osteoconductive effects of the two components. Furthermore, the malleable properties of the implant material during surgical applications for shape control will be enhanced. A critical size defect of 6 mm in diameter and 10 mm in depth was drilled into each distal femur of the rabbits. One hole was filled with the test substance and the other was left empty for control. After 1, 3, and 6 months the animals were killed and the degree of bone healing analyzed. In total, 18 animals were investigated. When the β-TCP composite was used, histological, histomorphometric, and biomechanical evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. Moreover, no signs of inflammation were observed in the animals and no allergic or foreign body reaction was noted. This suggests high biocompatibility and osteoconductivity of the investigated material to a bone void in an immune responsive species.

Bacteria rarely produce natural 2-phenylethanol. We verified a new pathway from Proteus mirabilis JN458 to produce 2-phenylethanol using Escherichia coli to coexpress l-amino acid deaminase, α-keto acid decarboxylase, and alcohol dehydrogenase from P. mirabilis. Based on this pathway, a glucose dehydrogenase coenzyme regeneration system was constructed. The optimal conditions of biotransformation by the recombinant strain E-pAEAKaG were at 40 °C and pH 7.0. Finally, the recombinant strain E-pAEAKaG produced 3.21 ± 0.10 g/L 2-phenylethanol in M9 medium containing 10 g/L l-phenylalanine after a 16 h transformation. Furthermore, when the concentration of l-phenylalanine was 4 g/L (24 mM), the production of 2-phenylethanol reached 2.88 ± 0.18 g/L and displayed a higher conversion rate of 97.38 mol %.

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