Hydroxysafflor Yellow A Reduced Neuroinflammation Induced by Astrocyte-Derived IL-17A by Inhibiting the IL-17RA/ACT1/NF-κB/IL-17A Loop After OGD/R.

Introduction: Neuroinflammation induced by astrocytes has garnered significant attention recently. The IL-17A/IL-17RA signal pathway plays an important role in ischemic stroke (IS). Hydroxysafflor yellow A (HSYA) has been reported to have anti-apoptotic and anti-inflammatory properties that can protect neurons. In this study, we explore a novel mechanism that underlies the anti-apoptotic and anti-inflammatory effects of HSYA. Methods: In vitro experiments were carried out using primary astrocytes and HT22 neuronal cells in an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Techniques such as Western blot, immunofluorescence staining, Enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to detect relevant indicators. The purpose was to investigate the effect of HSYA on the influence of IL-17A secreted by primary astrocytes after OGD/R on HT22 neuronal cells. Results: The results indicated that the production of IL-17A by astrocytes increased following OGD/R, which was reduced due to HSYA treatment. In addition, astrocyte-derived IL-17A resulted in neuronal cell damage. Further studies showed that HSYA reduced IL-17A production by inhibiting activation of the IL-17RA/ACT1/NF-κB/IL-17A loop, which ultimately alleviated neuroinflammation and reduced neuronal apoptosis. Discussion: These findings suggest that an activated loop indeed exists between IL-17A and IL-17RA/ACT1/NF-κB after OGD/R, and HSYA treatment alleviated IL-17A release from astrocytes after OGD/R by inhibiting the IL-17RA/ACT1/NF-κB/IL-17A loop. These results further emphasize the anti-inflammatory and neuroprotective effects of HSYA and suggest that it may be a promising drug for treating IS.