Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Department of Neurosurgery, The Jinjiang Municipal Hospital, Quanzhou, Fujian Province, China.
Oxid Med Cell Longev. 2022 Jun 2;2022:3099409. doi: 10.1155/2022/3099409. eCollection 2022.
Subarachnoid hemorrhage (SAH) is an acute cerebral vascular disease featured by oxidative insults and neuroinflammation. Cycloastragenol (CAG), the major active component of , 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.
蛛网膜下腔出血（SAH）是一种以氧化损伤和神经炎症为特征的急性脑血管病。环黄芪醇（CAG）是 的主要活性成分，具有广泛的生物学功能。然而，CAG 对 SAH 的潜在有益作用及其潜在的分子机制尚不清楚。在本研究中，我们从体内和体外两方面评估了 CAG 对 SAH 的脑保护作用及机制。结果表明，CAG 能显著抑制 SAH 引发的氧化损伤、炎症介质产生、小胶质细胞活化和中性粒细胞浸润。此外，CAG 改善了 SAH 后的神经功能，并减轻了神经元凋亡和变性。体外结果还揭示了 CAG 对神经元和小胶质细胞共培养系统的治疗作用。在机制上，CAG 通过上调沉默信息调节因子 1（SIRT1）的表达，抑制 FoxO1、核因子-κB 和 p53 乙酰化水平，从而抑制氧化、炎症和凋亡途径。相反，用 Ex527 预先抑制 SIRT1 可消除 CAG 在体内和体外 SAH 模型中的保护作用。总之，我们的研究结果表明，CAG 可能是一种很有前途和有效的 SAH 治疗药物候选物。
