Tianma Gouteng decoction-derived nanoparticles ameliorate blood-brain barrier permeability after ischemic stroke via regulating lncRNA OIP5-AS1 and S1PR1/ERK/MEK signaling axis

Background Increasing evidence suggests that herbal-derived exosome-like nanoparticles (ELNs) can easily cross biological barriers such as the blood-brain barrier (BBB). However, current understanding of ELNs application in ischemic stroke therapy is still in its infancy. Method We extracted nanoparticles (TGD-NPs) from Tianma Gouteng decoction (TGD) and characterized their morphology and main active compounds. Subsequently, the potential and functional mechanism of TGD-NPs in maintaining the integrity of the BBB were evaluated in middle cerebral artery occlusion (MCAO)-induced ischemic stroke model and oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated cell model. Result We successfully extracted NPs, which retains the main bioactive compounds of TGD: baicalin, emodin, gastrodin, and stachydrine. Functional studies indicated that in mouse MCAO model, TGD-NPs intervention was more effective than TGD preparations in maintaining the integrity of the BBB, reducing the infarct area, and improving the neurological function. Meanwhile, TGD-NPs treatment attenuated the decrease in cell viability caused by OGD/R, and it significantly enhanced expression of tight junction proteins (Occludin and ZO-1). Mechanistic exploration revealed that TGD-NPs markedly upregulated lncRNA OIP5-AS1 expression, and its beneficial effect was attributed to the activation of the S1PR1-ERK1/2-MEK1/2 signaling axis. Conclusion TGD-NPs are positive in maintaining BBB integrity and neurological function after ischemic stroke.