Ding Ye-Ling, Qiao Li-Jun, Fang Hao, Fan Ling-Ling, Wu Dan, Xu Jian-Peng, Lv Qi-Hong, Deng Min-Zhen, Qiu Yu-Hui, Zhou Zi-Yi, Huang Yan, Zheng Jia-Yi, Zhang Shi-Jie, Cai Ye-Feng
State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, Guangzhou, 510405, China.
Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Neurochem Res. 2025 Jun 13;50(3):201. doi: 10.1007/s11064-025-04452-5.
Hydroxysafflor Yellow A (HSYA), a water-soluble compound derived from the traditional Chinese medicine Carthamus tinctorius L., is known for its protective effects against cerebral ischemia/reperfusion(I/R) injury, though its mechanism remains unclear. This study investigated the effect of HSYA on cerebral I/R injury and its potential relation to pyroptosis. Adult male Sprague-Dawley rats were divided into sham-operated, model, and HSYA-treated groups. HSYA was administered as a pretreatment for 5 days before constructing the cerebral I/R injury model. Neurological function scores, TTC staining, HE staining, Nissl staining, immunofluorescence staining, SOD, GSH, GSH-Px, MDA, LDH Assays, PCR, western blotting, and ELISA were used to assess HSYA's effects. HSYA pretreatment improved neurological deficits and pathological state of brain tissue and reduced infarct area. It raised SOD, GSH, and GSH-Px activities, along with reduced MDA and LDH levels. Immunofluorescence staining and western blotting revealed that HSYA effectively inhibited the expression of NLRP3, AIM2, Pyrin, Cleaved-Caspase1, GSDMD, ASC, and HMGB1-related proteins. Additionally, ELISA results demonstrated that HSYA suppressed the release of IL18 and IL-1β inflammatory factors in serum. These findings suggest HSYA may alleviate ischemic stroke injury by inhibiting NLRP3, AIM2, and Pyrin inflammasome-mediated pyroptosis, offering a potential therapeutic strategy for cerebral I/R injury.
羟基红花黄色素A（HSYA）是一种从传统中药红花中提取的水溶性化合物，以其对脑缺血/再灌注（I/R）损伤的保护作用而闻名，但其作用机制尚不清楚。本研究探讨了HSYA对脑I/R损伤的影响及其与细胞焦亡的潜在关系。成年雄性Sprague-Dawley大鼠分为假手术组、模型组和HSYA治疗组。在构建脑I/R损伤模型前5天给予HSYA进行预处理。采用神经功能评分、TTC染色法、HE染色法、尼氏染色法、免疫荧光染色法、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）、乳酸脱氢酶（LDH）检测、聚合酶链反应（PCR）、蛋白质免疫印迹法和酶联免疫吸附测定（ELISA）来评估HSYA的作用。HSYA预处理改善了神经功能缺损和脑组织病理状态，并减小了梗死面积。它提高了SOD、GSH和GSH-Px的活性，同时降低了MDA和LDH水平。免疫荧光染色和蛋白质免疫印迹法显示，HSYA能有效抑制NLRP3、AIM2、 Pyrin、裂解的半胱天冬酶-1、gasdermin D（GSDMD）、凋亡相关斑点样蛋白（ASC）和高迁移率族蛋白B1（HMGB1）相关蛋白的表达。此外，ELISA结果表明，HSYA抑制了血清中白细胞介素18（IL-18）和白细胞介素-1β（IL-1β）炎症因子的释放。这些研究结果表明，HSYA可能通过抑制NLRP3、AIM2和Pyrin炎性小体介导的细胞焦亡来减轻缺血性脑卒中损伤，为脑I/R损伤提供了一种潜在的治疗策略。
