Targeting post-translational modifications by traditional Chinese medicine in cerebral ischemia-reperfusion injury:...

Globally, ischemic stroke is a major contributor to global mortality. Cerebral ischemia-reperfusion injury (CIRI) occurs as a pathophysiological event subsequent to blood flow restoration, which accelerates the transmission of pathological signals and exacerbates damage. Current medical interventions still carry certain risks. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target nature, offers distinctive advantages including multi-constituent profiles, pleiotropic targeting capabilities, and broad-spectrum regulatory characteristics. In clinical practice, TCM enables individualized treatment based on syndrome differentiation and pharmacological regulation, forming a disease management chain encompassing prevention, treatment, and functional rehabilitation, thereby demonstrating significant promise in the treatment of CIRI.

This review systematically examines how TCM formulas, active components, and characteristic TCM therapies regulate post-translational modifications (PTMs) to prevent and treat CIRI. The regulatory mechanisms involved include phosphorylation, acetylation, ubiquitination, and lactylation, thereby offering novel perspectives for treatment of CIRI.

Relevant literature was systematically retrieved from databases such as PubMed, Web of Science, CNKI, and Wanfang Database by employing search terms associated with stroke, CIRI, post-translational modifications, phosphorylation, acetylation, ubiquitination, and lactylation. The search covered relevant literature published between 2015 and 2025. The scientific names of medicinal plants were confirmed through the Medicinal Plant Names Services (MPNS, http://mpns.kew.org).

By regulating PTMs, including phosphorylation, acetylation, ubiquitination, and lactylation, TCM formulas, individual herbs, and monomeric compounds exert suppressive effects on the development and progression of CIRI.

PTMs represent key therapeutic targets in the treatment of CIRI. TCM demonstrates efficacy in counteracting CIRI. However, further exploration is needed to investigate the downstream targets of PTMs regulated by TCM and to elucidate the specific regulatory sites of PTMs during the development and progression of CIRI. Additionally, attention should be given to evaluating the potential adverse effects of TCM and closely monitoring individual variations in clinical application. Elucidating the complex regulatory networks and therapeutic targets of PTMs following CIRI remains a high priority.