Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

Abstract

Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.

Electroacupuncture promotes the recovery of rats with spinal cord injury by suppressing the Notch signaling pathway via the H19/ EZH2 axis

“…Our studies found EA promoted NSC proliferation by inhibiting Notch signaling pathway (Figures 7 and 8), suggesting inhibition of Notch signaling pathway would as a target to protect NSC apoptosis of SCI. Accoumulating evidence shows that inhibition of Notch signaling pathway can improve SCI, including γ-secretase blocker (58), resveratrol (59), and sodium tanshinone IIA silate (60). Our data support the idea that EA-mediated Notch signaling pathway activation in SCI.…”

A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids

“…Among the tanshinones in S. miltiorrhiza , tanshinone ⅡA (TⅡA) is considered the major active ingredient ( Fang et al, 2021 ). In 3T3-L1 cells and zebrafish TⅡA inhibited lipid accumulation ( Park et al, 2017 ), and the derivate sodium TⅡA silate is used in China for alleviating cardiovascular and coronary heart diseases ( Li et al, 2020b ). Both T I and TⅡA, differing in A-ring aromatization, are typical tetracyclic tanshinones featuring an ortho -quinone C-ring and a furan D-ring ( Figure 1 ), while cryptotanshinone (CT) and 15,16-dihydrotanshinone I (DTI) with dihydrofuran ring were believed to be their precursors, respectively ( Ma et al, 2021) .…”

Sodium Tanshinone IIA Sulfonate Promotes Spinal Cord Injury Repair by Inhibiting BSCB Disruption In Vitro and In Vivo

“…Studies show that STS can not only exert neuroprotective effects but also repair the BBB in stroke patients [25][26][27]. Our preliminary results indicated that STS restored BSCB function and rescued microvessels 7 days after SCI [28]. However, the therapeutic effects of STS in the early stages post-SCI remain to be elucidated.…”