College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
Metab Brain Dis. 2024 Jun;39(5):705-718. doi: 10.1007/s11011-024-01357-0. Epub 2024 May 25.
Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.
韩乌头（A. coreanum）是一种传统中药，已被证明可治疗缺血性中风（IS）。然而，韩乌头抗中风的机制目前尚不清楚。本研究旨在揭示韩乌头的作用机制。并研究生乌头（RA）、蒸乌头（SA）和用生姜和明矾炮制的乌头（GA）对治疗 IS 的药理作用机制。确定炮制后是否会影响疗效。用沙土鼠颈总动脉单侧结扎模拟 IS。测定沙土鼠 IS 后神经功能评分、梗死体积、氧化应激水平和炎症因子表达。Western blot 和免疫荧光分析评估相关蛋白的表达。代谢组学分析尿代谢物中与 IS 相关的代谢途径。RA、SA 和 GA 显著改善 IS 沙土鼠的梗死体积和行为评分，增加脑组织超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、一氧化氮（NO）的表达，降低丙二醛（MDA）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的含量。Western blot 和免疫荧光分析结果表明，RA、SA 和 GA 显著增加了 P-Akt、PI3K、HO-1 和 KEAP1 的表达。代谢组学研究鉴定出 112 种差异代谢物，包括 L-脯氨酸、核黄素、白三烯 D4 和 7-甲基黄嘌呤，它们可能是中风的生物标志物，涉及核黄素代谢、嘧啶代谢和嘌呤代谢等 14 条代谢途径。我们的研究结果表明，韩乌头通过 PI3K/Akt 和 KEAP1/NRF2 途径保护大脑免受缺血性损伤。炮制前后的韩乌头对沙土鼠 IS 脑损伤均有保护作用，炮制后韩乌头的疗效并未降低。甚至与 RA 相比，SA 具有更好的疗效。
