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Hydroxysafflor Yellow A Reduced Neuroinflammation Induced by Astrocyte-Derived IL-17A by Inhibiting the
Lijuan Song1,2, Jianlin Hua2,3, Kexin Liu2
1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, 030619, People's Republic of China.
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.