Effect of butylphthalide intervention on experimental autoimmune myositis in guinea pigs.

Idiopathic inflammatory myopathies are a group of rare muscular diseases that are characterized by acute, subacute or chronic proximal and symmetric muscle weakness, muscle fiber necrosis and infiltration of inflammatory cells, particularly activated CD8+ cytotoxic T cells and phagocytes. 3-n-butylphthalide (NBP) protects mitochondria and reduces the inflammatory response in multiple disease models. In myositis, it has remained elusive whether NBP can protect muscle cells from muscle fiber injury. Experimental autoimmune myositis (EAM) was induced in a total of 40 guinea pigs by myosin immunization. After 4 weeks, low- or high-dose NBP solution was intraperitoneally injected. Saline solution was used as a negative control. After 10 days, the clinical manifestations were assessed by determining rodent grasping power, histopathological changes, Ca2+-adenosinetriphosphatase (ATPase) activity by an ATPase kit, and mRNA expression of interferon (IFN)-γ, retinoic acid receptor-related orphan nuclear receptor (ROR)γt and forkhead box (Fox) p3 in muscle tissue by reverse-transcription quantitative polymerase chain reaction analysis. It was demonstrated that NBP improved the myodynamia of guinea pigs with EAM and reduced the pathological inflammatory cell infiltration in a dose-dependent manner. NBP improved the Ca2+-ATPase activity of the muscle mitochondrial membrane and muscle plasma membrane in animals with EAM. It also reduced the mRNA expression of IFN-γ and RORγt, and significantly increased the mRNA expression of Foxp3 in muscle tissue. These results provided a basis for the consideration of NBP as a novel agent for the treatment of myositis and other muscular diseases associated with autoimmunity and inflammation.

A Sphingosine-type cerebroside in Clavicorona pyxidata induce fruit body formation.

Clavicorona pyxidata is a wild edible and medicinal mushroom that is rich in bioactive natural products and has thus been extensively used as traditional medicine in China. The present study has determined that the organic crude extract prepared from a fermented culture of C. pyxidata imparted auto-inhibitory effects on mycelial growth and then induced the formation of fruiting bodies. By monitoring bioactivity, one compound was isolated via successive chromatography over silica gel, Sephadex LH-20, and Cl8-reversed phase silica gel and was identified as a known sphingosine-type cerebroside by nuclear magnetic resonance (NMR) and physicochemical data, namely, (4E, 8E)-N-D-2'-hydroxypalmitoyl-1-O-ß-D-glucopyranosyl-9-methyl-4,8-sphingadienine. The application of this cerebroside at a concentration of 200 µg/disc paper resulted in the inhibition of aerial hyphal growth of C. pyxidata. The findings of the present study indicated that this C. pyxidata cerebroside is a fruiting body-inducing substance (FIS).

Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database.

According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130)2 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist.