Alpinetin inhibits neuroinflammation and neuronal apoptosis via targeting the JAK2/STAT3 signaling pathway in spinal cord injury.

BACKGROUND: A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects that can significantly improve the recovery of motor function after spinal cord injury (SCI). Here, we explore the role and molecular mechanisms of Alpinetin on activating microglia-mediated neuroinflammation and neuronal apoptosis after SCI. METHODS: Stimulation of microglia with lipopolysaccharide (LPS) to simulate neuroinflammation models in vitro, the effect of Alpinetin on the release of pro-inflammatory mediators in LPS-induced microglia and its mechanism were detected. In addition, a co-culture system of microglia and neuronal cells was constructed to assess the effect of Alpinetin on activating microglia-mediated neuronal apoptosis. Finally, rat spinal cord injury models were used to study the effects on inflammation, neuronal apoptosis, axonal regeneration, and motor function recovery in Alpinetin. RESULTS: Alpinetin inhibits microglia-mediated neuroinflammation and activity of the JAK2/STAT3 pathway. Alpinetin can also reverse activated microglia-mediated reactive oxygen species (ROS) production and decrease of mitochondrial membrane potential (MMP) in PC12 neuronal cells. In addition, in vivo Alpinetin significantly inhibits the inflammatory response and neuronal apoptosis, improves axonal regeneration, and recovery of motor function. CONCLUSION: Alpinetin can be used to treat neurodegenerative diseases and is a novel drug candidate for the treatment of microglia-mediated neuroinflammation.

Coating of Epimedii Folium Water Extract onto TiO2 Nanotube Surfaces Promotes Differentiation and Proliferation of Osteoblasts.

The surface modification of titanium is effective in promoting osseointegration and is widely used in the treatment of bone diseases. Epimedii Folium (EF) plays an important role in the treatment of metabolic bone diseases. However, few studies have so far been reported on their combined use in such treatments. In the present study, EF water extract was coated onto the surface of TiO2 nanotubes (TNT) by electrochemical anodization to obtain EF-TNT. Through analysis of surface morphology characteristics, it was demonstrated that EF was successfully coated on the surface of TiO2 nanotubes. In vitro drug release data suggested that the quantity of EF water extract released was a significant quantity over 4 days, reaching a total of 80%, the release continuing in total for approximately 2 weeks. By using scanning electron microscopy and immunofluorescent staining, it was found that, EF-TNT more strongly promoted adhesion, proliferation, and differentiation of MC3T3-E1 osteoblasts compared with Ti and TNT. Quantitative reverse transcript polymerase chain reaction (qRT-PCR) analysis indicated that the expression of key genes for proliferation and differentiation of osteoblasts, such as COL1a1, ALP, OPN, and Runx2, were up-regulated by EF-TNT. Network pharmacology analysis suggested that EF water extract not only regulated the proliferation and differentiation of osteoblasts but also caused a regulatory effect on osteoclasts via multiple signaling pathways, such as RANKL-RANK-induced signaling and TGF-ß signaling. These findings indicate that the EF-TNT promotes differentiation and proliferation of osteoblasts, and represents considerable potential for use in clinical applications.