Modulation of miRNAs by Phytochemicals in Cerebral Ischemia: A Systematic Review of In Vitro and In Vivo Studies.

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.