Hydroxysafflor Yellow A exerts neuroprotective effects by inhibiting astrocyte-derived IL-17 after OGD/R

Background: Stroke is the second most common cause of death worldwide, but currently, there exists no effective treatment for stroke. The inflammatory response is a key component of post-stroke and secondary injury. As an inflammatory factor involved in stroke injury, interleukin 17 (IL-17) has become a research hotspot. Hydroxysafflor yellow A (HSYA) has anti-ischemic, anti-oxidation, anti-thrombotic, and anti-inflammatory effects, but whether it has any effect on astrocyte (Ast)-derived IL-17 after cerebral ischemia and hypoxia remains unclear. Its protective effect of neuronal damage caused by IL-17 has not yet been studied. Therefore, in this study, we sought to determine the effect of HSYA on IL-17 and its underlying mechanism, with the aim to provide new ideas for the treatment of ischemic stroke. Methods: The oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary Asts was established, and the effect of HSYA on Ast-derived IL-17 was further verified by experimental methods including Reverse Transcription-Polymerase Chain Reaction（RT-PCR）, enzyme-linked immunosorbent assay（ELISA）, immunofluorescence and western blot. PC12 cells were cultured with the supernatant of OGD/R astrocytes as conditioned medium for 24h. Lactate dehydrogenase（LDH） and Terminal deoxynucleotidyl transferase dUTP nick end labeling（TUNEL) were detected the effect of astrocyte derived IL-17 on PC12 cells. Results: The expression of IL-17 in Asts in the OGD/R group was increased but was decreased after the addition of HSYA. The expression of LCN2 was inhibited, and the inflammatory response and neuronal damage induced by OGD/R were also reduced. PC12 cells were damaged after culturing with Ast-conditioned medium for 24 h; however, the damage was significantly reduced after adding IL-17 neutralizing antibody (ixekizumab antibody) or HSYA. Conclusion: HSYA can inhibit the expression of IL-17 derived from Ast after OGD/R and reduce the binding of IL-17 to IL-17 receptors, thereby protecting neurons. This work was supported by research grants from the National Natural Science Foundation of China (No. 82004028 to L.-J.S., No. 81473577 to C.M.), Innovative Young Talent Team of Shanxi Science and Technology Department (202204051001028 to L.-J.S.), Grant of Zhang Zhongjing Legacy and innovation of State Administration of Traditional Chinese Medicine (GZY-KJS-2022-048-1to L.-J.S.), Young Scientists Cultivation Project of Shanxi University of Chinese Medicine (2021PY-QN-09 to L.S.), Innovation Team of Shanxi University of Chinese Medicine (2022TD2010 to L.S.), Science and Technology Innovation Cultivation Plan of Shanxi University of Chinese Medicine (2022PY-ZBK-006 to L.S.), Leading Team of Medical Science and Technology, Shanxi Province (2020TD05 to C.M.), China Postdoctoral Science Foundation (2020M680912 to L.S.), Cardiovascular special fund project of national regional traditional Chinese medicine medical center of Affifiliated Hospital of Shanxi University of Chinese Medicine in 2021 (XGZX202115 to L.S.), “Basic research project” of the cultivation plan of scientifific and technological innovation ability of Shanxi University of Chinese Medicine (2020PY-JC-02 to L.S.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.