Andrographolide Attenuates Blood-Brain Barrier Disruption, Neuronal Apoptosis, and Oxidative Stress Through Activation of Nrf2/HO-1 Signaling Pathway in Subarachnoid Hemorrhage
Andrographolide Attenuates Blood-Brain Barrier Disruption, Neuronal Apoptosis, and Oxidative Stress Through Activation of Nrf2/HO-1 Signaling Pathway in Subarachnoid Hemorrhage
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DOI：
10.1007/s12640-022-00486-7
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发表时间：
2022-03-19
影响因子：
3.7
通讯作者：
Li, Mingchang
中科院分区：
文献类型：
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作者：
Gong, Pian;Zhang, Wei;Li, Mingchang
穿心莲内酯 (Andro) 是从亚洲植物穿心莲中提取的拉丹烷家族的二萜，具有神经保护作用，可预防中风和阿尔茨海默病。然而，Andro 是否能保护大脑免受蛛网膜下腔出血（SAH）的影响仍不清楚。因此，我们在体外和体内探索了 Andro 是否可以减轻血脑屏障 (BBB) 破坏和神经元凋亡并抑制氧化应激以保护大脑免受 SAH 的影响，并在本研究中检测 Andro 神经保护作用的潜在机制。使用氧合血红蛋白 (OxyHb) 处理的神经元 PC12 细胞作为体外模型。使用 Sprague-Dawley 大鼠建立体内模型。此外，我们使用血红素加氧酶-1（HO-1）（ZnPPIX）抑制剂进行体外和体内实验，以评估核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）级联是否是Andro对抗SAH的一种保护性分子机制。我们的结果表明，在体外，Andro 增加了 OxyHb 处理的神经元 PC12 细胞的细胞活力、抑制细胞凋亡并激活 Nrf2/HO-1 级联。在体内，Andro 可减轻神经功能障碍、神经元凋亡、血脑屏障破坏、脑水肿和氧化应激，并激活 Nrf2/HO-1 通路。 ZnPPIX 在体外和体内逆转了 Andro 的作用。我们的研究表明，Andro 可能通过 Nrf2/HO-1 信号通路减轻 SAH 中的 BBB 破坏、神经元凋亡和氧化应激。
Andrographolide (Andro), a diterpene of the labdane family extracted from the Asian plant Andrographis paniculata, is neuroprotective against stroke and Alzheimer's disease. However, whether Andro protected the brain against subarachnoid hemorrhage (SAH) was still unknown. Thus, we explored whether Andro attenuated blood-brain barrier (BBB) disruption and neuronal apoptosis and inhibited oxidative stress to protect the brain against SAH both in vitro and in vivo and detected underlying mechanisms of Andro's neuroprotective effects in the present study. Oxyhemoglobin (OxyHb)-treated neuronal PC12 cells were used as an in vitro model. An in vivo model was established using Sprague-Dawley rats. Moreover, we used an inhibitor of heme oxygenase-1 (HO-1) (ZnPPIX) in vitro and in vivo experiments to evaluate whether the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade acted as one protective molecular mechanism of Andro against SAH. Our results revealed that, in vitro, Andro increased cell viability, inhibited apoptosis, and activated Nrf2/HO-1 cascade of neuronal PC12 cells treated with OxyHb. In vivo, Andro attenuated the neurological dysfunction, neuronal apoptosis, BBB disruption, brain edema, and oxidative stress and activated the Nrf2/HO-1 pathway. ZnPPIX reversed the effects of Andro in vitro and in vivo. Our research suggested that Andro alleviated BBB disruption, neuronal apoptosis, and oxidative stress in SAH, possibly via the Nrf2/HO-1 signaling pathway.