Rzemieniec Joanna, Marino Mirko, Mercuriali Benedetta, Castiglioni Laura, Gelosa Paolo, Muluhie Majeda, Del Bo' Cristian, Riso Patrizia, Sironi Luigi
Department of Pharmaceutical Sciences, Università Degli Studi di Milano, Milan, Italy.
Department of Food, Environmental and Nutritional Sciences (DeFENS), Division of Human Nutrition, Università Degli Studi di Milano, Milan, Italy.
Phytother Res. 2025 Sep;39(9):4327-4347. doi: 10.1002/ptr.70062. Epub 2025 Aug 13.
Phytochemicals gained substantial interest for their protective action in cerebral ischemia. Additionally, there is a growing body of evidence suggesting that miRs play a role in stroke therapy. However, no systematic review to date has summarized the impact of phytochemicals on miRs modulation and their role in protecting the brain against ischemia. This systematic review aims to assess the current literature on the protective action of phytochemicals in cellular and animal models of stroke, with special focus on the miRs modulation. A literature search was conducted across three databases (PubMed, Scopus, Embase), adhering to PRISMA guidelines. Studies published in English between 2014 and 2024 were included based on relevant keywords. A total of 224 articles were excluded based on their title and/or abstract as they were deemed irrelevant. Furthermore, 4 articles were excluded due to the lack of an English or full-text version. Finally, 14 articles were included in this review. Phytochemicals reverted ischemia-induced changes in miRs expression; that is, they upregulated miR-556-3p, miR-223-3p, miR-1287-5p, miR-214, miR-96, miR-450b-5p, miR-149-5p, miR-375, and downregulated miR-145-5p, miR-124, miR-128-3p, miR-122, miR-181b, miR-155, miR-134, and miR-128-3p. These, in turn, led to an inhibition of apoptosis, inflammation, oxidative stress, ferroptosis, pyroptosis, and activation of Wnt and AMPK signaling. Our analysis indicates that targeting miRs with phytochemicals may inhibit the ischemic injury; thus, it represents a promising tool for the development of new therapeutic strategies for stroke. Given that all of the reviewed studies utilized cellular or animal models, further human clinical trials are necessary to confirm these findings.
植物化学物质因其在脑缺血中的保护作用而备受关注。此外，越来越多的证据表明，微小RNA（miRs）在中风治疗中发挥作用。然而，迄今为止，尚无系统综述总结植物化学物质对miRs调节的影响及其在保护大脑免受缺血损伤中的作用。本系统综述旨在评估当前关于植物化学物质在中风细胞和动物模型中保护作用的文献，特别关注miRs调节。按照PRISMA指南，在三个数据库（PubMed、Scopus、Embase）中进行了文献检索。根据相关关键词纳入2014年至2024年期间发表的英文研究。共有224篇文章因其标题和/或摘要被认为不相关而被排除。此外，4篇文章因缺乏英文或全文版本而被排除。最后，本综述纳入了14篇文章。植物化学物质逆转了缺血诱导的miRs表达变化；也就是说，它们上调了miR-556-3p、miR-223-3p、miR-1287-5p、miR-214、miR-96、miR-450b-5p、miR-149-5p、miR-375，并下调了miR-145-5p、miR-124、miR-128-3p、miR-122、miR-181b、miR-155、miR-134和miR-128-3p。这些变化进而导致细胞凋亡、炎症、氧化应激、铁死亡、焦亡受到抑制，以及Wnt和AMPK信号通路被激活。我们的分析表明，用植物化学物质靶向miRs可能抑制缺血性损伤；因此，它是开发中风新治疗策略的一个有前景的工具。鉴于所有综述研究均使用细胞或动物模型，有必要进行进一步的人体临床试验来证实这些发现。
