异甘草素
药理学
氧化应激
神经保护
锡尔图因
医学
西妥因1
化学
内科学
生物化学
下调和上调
乙酰化
基因
作者
Jiaqiang Liu,Xintong Zhao,Feiyun Qin,Jia-Wang Zhou,Fei Ding,Gang Zhou,Xiangsheng Zhang,Zihuan Zhang,Zhen-Bao Li
出处
期刊:Phytomedicine
[Elsevier]
日期:2022-06-21
卷期号:105: 154262-154262
被引量:33
标识
DOI:10.1016/j.phymed.2022.154262
摘要
Oxidative stress is a crucial factor leading to subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). Isoliquiritigenin has been verified as a powerful anti-oxidant in a variety of diseases models and can activate sirtuin 1 and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, the effects of isoliquiritigenin against EBI after SAH and the underlying mechanisms remain elusive.The primary goal of this study is to verify the therapeutic effects of isoliquiritigenin on EBI after SAH and the possible molecular mechanisms.A prechiasmatic cistern SAH model in rats and a hemoglobin incubation SAH model in primary neurons were established. Isoliquiritigenin was administered after SAH induction. EX527 was employed to inhibit sirtuin 1 activation and ML385 was used to suppress Nrf2 signaling.In our study, neurological scores, brain edema, biochemical estimation, western blotting, and histopathological study were performed to explore the therapeutic action of isoliquiritigenin against SAH.Our data revealed that isoliquiritigenin significantly mitigated oxidative damage after SAH as evidenced by decreased reactive oxygen species overproduction and enhanced intrinsic anti-oxidative system. Concomitant with the reduced oxidative insults, isoliquiritigenin improved neurological function and reduced neuronal death in the early period after SAH. Additionally, isoliquiritigenin administration significantly enhanced Nrf2 and sirtuin 1 expressions. Inhibition of Nrf2 by ML385 reversed the anti-oxidative and neuroprotective effects of isoliquiritigenin against SAH. Moreover, inhibiting sirtuin 1 by EX527 pretreatment suppressed isoliquiritigenin-induced Nrf2-dependent pathway and abated the cerebroprotective effects of isoliquiritigenin. In primary cortical neurons, isoliquiritigenin treatment also ameliorated oxidative insults and repressed neuronal degeneration. The beneficial aspects of isoliquiritigenin were attributed to the promotion of sirtuin 1 and Nrf2 signaling pathways and were counteracted by EX527.Our findings suggest that isoliquiritigenin exerts cerebroprotective effects against SAH-induced oxidative insults by modulating the Nrf2-mediated anti-oxidant signaling in part through sirtuin 1 activation. Isoliquiritigenin might be a new potential drug candidate for SAH.
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