Subarachnoid hemorrhage (SAH) is an acute cerebral vascular disease featured by oxidative insults and neuroinflammation. Cycloastragenol (CAG), the major active component of Astragalus radix, has a wide range of biological functions. However, the potential beneficial effects and the underlying molecular mechanisms of CAG on SAH remain obscure. In the current study, the cerebroprotective effects and mechanism of CAG on SAH were evaluated both in vivo and in vitro. Our results indicated that CAG significantly suppressed SAH-triggered oxidative insults, inflammatory mediators production, microglia activation, and the neutrophil infiltration in the brain. In addition, CAG improved neurological function and ameliorated neuronal apoptosis and degeneration after SAH. In vitro results also revealed the therapeutic effects of CAG on neurons and microglia co-culture system. Mechanistically, CAG treatment upregulated sirtuin 1 (SIRT1) expression, inhibited the levels of FoxO1, nuclear factor-kappa B, and p53 acetylation, and suppressed the subsequent oxidative, inflammatory, and apoptotic pathways. In contrast, inhibiting SIRT1 by pretreatment with Ex527 abrogated the protective actions of CAG both in vivo and in vitro models of SAH. Collectively, our findings indicated that CAG could be a promising and effective drug candidate for SAH.
Subarachnoid hemorrhage (SAH) as a devastating neurological disorder is closely related to heightened oxidative insults and neuroinflammatory injury. Pinocembrin, a bioflavonoid, exhibits different biological functions, such as immunomodulatory, anti-inflammatory, antioxidative, and cerebroprotective activities. Herein, we examined the protective effects and molecular mechanisms of pinocembrin in a murine model of SAH. Using an endovascular perforation model in rats, pinocembrin significantly mitigated SAH-induced neuronal tissue damage, including inflammatory injury and free-radical insults. Meanwhile, pinocembrin improved behavior function and reduced neuronal apoptosis. We also revealed that sirtuin-1 (SIRT1) activation was significantly enhanced by pinocembrin. In addition, pinocembrin treatment evidently enhanced peroxisome proliferator-activated receptor-γ coactivator expression and suppressed ac-nuclear factor-kappa B levels. In contrast, EX-527, a selective SIRT1 inhibitor, blunted the protective effects of pinocembrin against SAH by suppressing SIRT1-mediated signaling. These results suggested that the cerebroprotective actions of pinocembrin after SAH were through SIRT1-dependent pathway, suggesting the potential application of pinocembrin for the treatment of SAH.
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