Jiang Guang-You, Yang Hong-Rui, Li Chen, Liu Nan, Ma Sheng-Ji, Jin Bing-Xuan, Yan Cong, Gong Hai-Dong, Li Ji-Yi, Yan Hao-Chen, Ye Guang-Xi, Wang Wen-Yu, Gao Cheng
Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China; Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Free Radic Biol Med. 2025 Feb 16;228:299-318. doi: 10.1016/j.freeradbiomed.2024.12.058. Epub 2024 Dec 31.
Ferroptosis, a recently identified form of regulated cell death, is characterized by lipid peroxidation and iron accumulation, plays a critical role in early brain injury after subarachnoid hemorrhage. Ginsenoside Rd, an active compound isolated from ginseng, is known for its neuroprotective properties. However, its influence on SAH-induced ferroptosis remains unclear. In this study, we constructed an SAH model using intravascular perforation in vivo and treated HT22 cells with oxyhemoglobin to simulate the condition in vitro. We observed significant changes in ferroptosis markers, including GPX4 and ACSL4, following SAH. Administration of ginsenoside Rd to both rats and HT22 cells effectively inhibited neuronal ferroptosis induced by SAH, alleviating neurological deficits and cognitive dysfunction in rats. Notably, the neuroprotective properties of ginsenoside Rd were countered by the STING pathway agonist 2'3'-cGAMP. Experiments conducted in vitro and in vivo illustrated that the impacts of ginsenoside Rd were counteracted by the BQR inhibitor. Our findings suggest that ginsenoside Rd mitigates EBI after SAH by suppressing neuronal ferroptosis through the cGAS/STING pathway while upregulating DHODH levels. These outcomes emphasize the potential of ginsenoside Rd as a therapeutic candidate for subarachnoid hemorrhage.
铁死亡是一种最近发现的程序性细胞死亡形式，其特征是脂质过氧化和铁蓄积，在蛛网膜下腔出血后的早期脑损伤中起关键作用。人参皂苷Rd是从人参中分离出的一种活性化合物，以其神经保护特性而闻名。然而，其对蛛网膜下腔出血诱导的铁死亡的影响仍不清楚。在本研究中，我们在体内使用血管内穿孔构建了蛛网膜下腔出血模型，并在体外使用氧合血红蛋白处理HT22细胞以模拟该情况。我们观察到蛛网膜下腔出血后铁死亡标志物（包括GPX4和ACSL4）有显著变化。给大鼠和HT22细胞施用人参皂苷Rd可有效抑制蛛网膜下腔出血诱导的神经元铁死亡，减轻大鼠的神经功能缺损和认知功能障碍。值得注意的是，STING途径激动剂2'3'-cGAMP可抵消人参皂苷Rd的神经保护特性。体外和体内实验表明，BQR抑制剂可抵消人参皂苷Rd的作用。我们的研究结果表明，人参皂苷Rd通过cGAS/STING途径抑制神经元铁死亡，同时上调DHODH水平，从而减轻蛛网膜下腔出血后的早期脑损伤。这些结果强调了人参皂苷Rd作为蛛网膜下腔出血治疗候选药物的潜力。
